ASCO Daily News

By American Society of Clinical Oncology (ASCO)

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The ASCO Daily News Podcast features oncologists discussing the latest research and therapies in their areas of expertise.

Episode Date
Dr. Larissa Korde Discusses the Implications of the New USPSTF Recommendations on Risk Assessment, Genetic Testing for BRCA Genes
Dr. Larissa Korde Discusses the Implications of the New USPSTF Recommendations on Risk Assessment, Genetic Testing for BRCA Genes
Sep 12, 2019
Dr. Linda Bosserman Highlights Key Presentations from ASCO's Oncology Practice Conference
Dr. Linda Bosserman Highlights Key Presentations from ASCO's Oncology Practice Conference
Sep 12, 2019
Dr. Karen Tedesco Discusses How the IMpassion130 Study Will Inform Metastatic Triple-Negative Breast Cancer Care
Welcome to the ASCO Daily News Podcast. I'm Lauren Davis, and joining me today is Dr. Karen Tedesco of New York Oncology Hematology to discuss the impassioned 130 results in triple negative breast cancer. Today, we are discussing this aggressive form of breast cancer that is particularly difficult to treat because it's unresponsive to hormone and HER2-targeted therapies, leave patients with limited treatment options and a poor prognosis. Dr. Tedesco, welcome to the podcast. Thank you, Lauren. It's a pleasure to be here. An important treatment advance came in March 2019 when the FDA granted accelerated approval of atezolizumab, the first cancer immunotherapy regimen for breast cancer. Could you speak to the phase 3 and IMpassion 130 results, which led to the approval of this drug, in addition to the broader treatment landscape? Yes, so the IMpassion 130 trial was a multi-center, international, double-blind, placebo-controlled randomized trial that included 902 patients who had locally advanced or unresectable metastatic breast cancer that had the triple negative profile, the ER, PR, and HER2 all being negative. The patients could not have received chemotherapy for metastatic disease previously, but could have received chemotherapy in the adjuvant setting, including a taxane, as long as it was a year or more prior to enrollment in this study. And the study looked at the atezolizumab or a placebo given on days 1 and 15 every 28 days in conjunction with Nanoparticle Albumin-Bound, or NAB, paclitaxel at 100 milligrams per meter squared given on days 1, 8, and 15 of an every 28-day cycle. And they prospectively assessed for PD-L1 expression and called positive anything that expressed over 1% of the tumor area staining for the PD-L1 was considered a positive. And in patients whose tumors expressed the PD-L1, the median progression-free survival was 7.4 months for the treatment arm, including the atezolizumab and NAB paclitaxel, and 4.8 months for those that received the NAB paclitaxel plus placebo. The progression-free survival hazard ratio was 0.6 with a p value of less than 0.001 in favor of the treatment arm with the atezolizumab. The objective response rate was 53%, as compared to 33% for patients who received the atezolizumab and those who received the placebo. The overall survival data was not mature at this time, but when this trial was published in the New England Journal of Medicine in October of 2018, for the intention to treat population, median overall survival was 21.3 months with the atezolizumab and NAB paclitaxel compared to 17.6 months for the NAB paclitaxel and placebo. And for patients who had tumors that were PD-L1-positive, the median overall survival was 25 months for those who received the atezolizumab with the NAB paclitaxel as opposed to 15.5 months for those who received the NAB paclitaxel and placebo. So I'm curious. Do patients have immediate access to this treatment? Yes, they do. I've ordered this for a couple of my patients now since the time of this approval, and I've not had any difficulties in terms of getting approval for the medication. I will say, particularly for those of us in smaller communities, I think the biggest obstacle is getting the PD-L1 testing done and communicating with pathologists about the particular companion diagnostic test, the Ventana PD-L1 Assay that was approved in conjunction with approval of this regimen. So for me, I think that's been the biggest delay in access for the patients. But when I've ordered the medications, they were able to get them right away. That's great. We always wonder about side effects, so what should specialists tell their patients? So many of the most common side effects on this trial were actually those that we would probably think of as being more typical of the NAB paclitaxel, so alopecia, peripheral neuropathies, nausea, fatigue, neutropenia, decreased appetite. Certainly with any of the immune therapies, as many of us are getting more familiar, there are some toxicities we have to be aware of that are different than typical chemotherapy, and those largely include autoimmune-mediated toxicities So in this particular trial, there were some autoimmune-mediated hypothyroidism episodes, and those can be pretty easily managed. There was one autoimmune hepatitis that was quite severe. Other autoimmune toxicities I think we need to be mindful of include pneumonitis and colitis, both of which were rare on this trial. And rashes can be another thing. So even though this is the first immunotherapy approved for breast cancer treatment, many of us who treat other types of cancers out in the community are certainly gaining a lot of familiarity with these type of drugs. So I don't think anything was seen in terms of toxicities on this trial that was unanticipated. That's good to know. Were there any surprises in the trial results? I didn't think there were any surprises. I was happy to see that favorable results seemed to correlate with PD-L1 expression because again, I think that gives us a marker to look at for our patients and hopefully be able to best advise patients, depending on their molecular testing, whether a treatment is likely to be helpful to them or not so that we're not subjecting someone to needless toxicity if they're not likely to get significant benefit from the addition of a new drug. That's true. What do you think's on the horizon for breast cancer studies? Well, I think in the realm of immunotherapy, certainly there are going to be other immunotherapy drugs, likely in combination with chemotherapy, that are being looked at. There's going to be more studies coming out about immunotherapies in the neoadjuvant setting, particularly for the triple-negative profile breast cancer because that complete pathologic response can be a good surrogate in some instances for other outcomes and can more rapidly generate information. I think with triple-negative breast cancer in general, what we're learning more about is that we can't just lump all these patients with triple-negative profile together as if they're one homogeneous group just because they don't express estrogen, and progesterone, and HER2 receptors on their breast cancer. So some of these, I think we're trying to identify what makes them unique and what particular drugs might be good targets for them. So some of these triple-negative profile breast cancers may have androgen receptor expression and potentially respond well to anti-androgenic hormonal therapies, like we would use in prostate cancer, so things like bicalutamide, or enzalutamide, or understudy. PARP inhibitors are being looked at more in the triple-negative profile breast cancers, particularly those for women who have germline BRCA mutations, and even those who may have somatic BRCA mutations, or other types of mutations like PALB2 in their tumor. So as we're doing more gene expression profiles on tumor, that can help us identify some appropriate targets for these patients with this oftentimes difficult-to-treat profile of breast cancer. Absolutely. Again, today my guest has been Dr. Karen Tedesco. Thank you so much for being on our podcast today. Thank you, Lauren. And to our listeners, thank you for tuning into the ASCO Daily News Podcast. If you're enjoying the content, we encourage you to subscribe, rate, and review us on Apple Podcasts.
Aug 22, 2019
Spanish Language Discussion of Developmental Therapeutics, New Drugs, and Phase I Highlights From the ASCO Annual Meeting
Spanish Language Discussion of Developmental Therapeutics, New Drugs and Phase I Highlights From the ASCO Annual Meeting with Dr. Gilberto Lopes and Dr. Christian Rolfo.
Aug 08, 2019
Dr. Neelima Denduluri Highlights Key Poster Presentations in Breast Cancer from ASCO's Annual Meeting
[MUSIC PLAYING] Welcome to the ASCO Daily News podcast. I'm Lauren Davis. And joining me today is Dr. Neelima Denduluri, a medical oncologist and Associate Chair of Breast Cancer for the US Oncology Network. Dr. Denduluri, welcome to the podcast. Thank you for having me. We're glad you're here. Today, we're talking about stand out poster presentations from the ASCO annual meeting that really stood out to you. Can you tell me a little bit what was interesting about this year's meeting? I really enjoyed this year's ASCO because I thought there was a lot of focus on survivorship, prevention, and really focusing on our patients across the cancer care continuum. With regards to supportive care and what we do during treatment to make sure that our patients get through their treatments include reducing their risk of their blood counts dropping from chemotherapy. A way that we often employ preoperative chemotherapy or adjuvant chemotherapy is in the dose-dense fashion, meaning that we give the chemotherapy at more rapid intervals. And one thing we've always wondered is, do we really need to use growth factor in a very commonly used regimen, the dose-dense AC paclitaxel regimen? And interestingly, abstract 517 confirmed something that a lot of us have been doing in practice. And that is that for patients that don't have high risk of neutropenic fever, they don't need pegfilgrastim to reduce their risk of complications from paclitaxel being given in a dose-dense fashion. I think that from a quality of life perspective for patients, that is dramatic. As we know, filgrastim and pegfilgrastim do cause arthralgias, low-grade fevers. And I thought that this was a step in the positive direction that we finally have data that suggests that we really don't need to use it in the paclitaxel portion in most of our patients. Additionally, it reduces the financial toxicity that our early breast cancer survivors have to go through as well. Similarly, one thing that our patients struggle with is diarrhea with a drug that we use for HER2 positive breast cancer in the early breast cancer setting called neratinib. And one limiting issue with neratinib has always been the diarrhea. The control study, which was abstract number 548, showed that those patients that we adequately recognized and educated them in saying, listen, diarrhea is an issue with neratinib, and we gave them prophylactic loperamide-- this trial also added budesonide and colestipol to loperamide prophylaxis for one to two cycles-- and found that it reduces the severity and duration of the diarrhea in those patients being treated with neratinib for their HER2 positive breast cancer. So I thought both of these were really interesting in terms of moving the field forward in terms of tolerability. And one is to de-escalate care. And one is to escalate care. So I want to shift gears a little bit to a subtype of breast cancer that we often focus on, triple negative breast cancer, to improve outcomes. We know that chemotherapy is paramount in this disease to reduce the risk of recurrence and improve disease free and overall survival in the early breast cancer setting. One thing that we don't know is who we need to add carboplatin to in addition to standard anthracycline and taxane-containing therapy to improve outcomes. There have been multiple studies that have looked at this. And there are some confirmatory trials looking at this in the early breast cancer setting as well. One trial I want to highlight is the CALGB Alliance trial, which was presented in abstract 591. And what it showed was that regardless of treatment arm, pathologic complete response was associated with markedly better long-term outcomes. We also know that patients with any residual disease had significantly worse outcomes. Now, when looking at the whole population, the addition of carboplatin to standard neoadjuvant chemotherapy did not improve long-term outcomes. Additionally, it led to omission of standard chemotherapy doses such as paclitaxel in the patients that were treated with carboplatin. We know that dose density and dose intensity are very important to long-term survivals in triple negative breast cancer. So therefore, I thought that this was an interesting point that the authors made sure to make that the anthracycline and the taxane-containing part is very important. And if we add carboplatin, which is a very personalized decision, we need to make sure that the dose and that intensity and dose density are maintained because patients, they have worse outcomes. If the carboplatin is added, they have cytopenias, and we have to stop both the paclitaxel and the carboplatin. Sounds like a lot of promising presentations this year. Any surprising results? I don't think there were any surprising results. However, it was very gratifying, again, that certain subtypes of breast cancer are being looked at more closely. For example, abstract 546 looked at adjuvant enzalutamide for the treatment of early stage androgen receptor positive triple negative breast cancer. Growing research shows that triple negative breast cancer is a very heterogeneous disease. And this trial nicely took patients that received their standard adjuvant therapy. And then these patients went on to receive enzalutamide, which targets the androgen receptor, for one year. And the authors showed that it was very tolerable. And the enzalutamide side may be the next step in how we improve outcomes for this special subtype of triple negative breast cancer. Another abstract that was very interesting was abstract 552 that looked at the rates of osteonecrosis of the jaw in woman with breast cancer receiving bisphosphonates to prevent breast cancer metastases. We've always historically used bisphosphonates in the advanced breast cancer setting. However, we're increasingly using it in the early breast cancer setting. And it was gratifying to see that the prevalence of the osteonecrosis of the jaw was very low and patients that, for example, had dentures, or plaques, or chemotherapy, or corticosteroid use were not at higher risk for osteonecrosis of the jaw. I thought this was reassuring for our highest risk early breast cancer patients. Something else that we know from the breast cancer literature is that many of our patients have trouble adhering to adjuvant endocrine therapy. And that's very important in terms of improving outcomes. And there was a study, abstract 523, that showed that possibly patients that were in urban settings had lower adherence to adjuvant endocrine therapy. Additionally, patients that were ages between 41 and 74 were more likely to adhere to their adjuvant endocrine therapy. That was reassuring. However, we as a community need to do better at improving tolerability. We know that acupuncture, duloxetine, yoga, regular exercise, possibly vitamin D may also improve tolerability to these medications. One small feasibility abstract that I found interesting was 525, which enrolled 60 patients to receive tart cherry extract and showed that the patients that received the tart cherry extract actually had improved symptoms in terms of musculoskeletal symptoms from receiving this. Wow. So I thought that's hopeful. And that's kind of surprising in terms of moving the field forward in terms of tolerability, coming up with novel ideas to try and improve adherence to these medications. Absolutely. That leads in a little bit to my next question, which is, how do you talk to your patients about what you've seen and heard at the annual meeting? One thing that our patients always want to know after the annual meeting when I come back is, what did you learn, and how does it affect me? And I tell them that there are three major themes. One is all of these stress to us that we as providers need to do a better job in terms of improving tolerability to these medications, that we are looking at this, and there's a lot of great research to help with us. Second thing that we talk about is that the science is always dynamic. So what I may have said to you three years ago may change how I treat you now. And then for our new breast cancer patients, one thing that has come up, I think, and has been reiterated is that we really need to make sure and incorporate our care in a multidisciplinary fashion not only with the surgeons, the radiation oncologists, which is a team we've always traditionally made sure to include, but also our primary care physicians, our gynecologists to improve tolerability. That's great. What do you think is on the horizon for breast cancer care? I think that this is a phrase that we often use but I think that further personalization of therapy. For example, in the last eight months, I think that the way that we treat, for example, early HER 2 positive breast cancer has transformed significantly in that majority of patients that are treated for early breast cancer, now, we meet them upfront before their surgery to discuss whether we should give chemotherapy up front with HER 2 targeted therapy, or should we give it to them after surgery? And that's because we know that, those patients that don't achieve a pathologic complete response to HER 2 targeted therapy and chemotherapy, that we need to escalate their care, switch their care to other agents. So I think that there's going to be more of that in various subtypes of breast cancer in terms of more personalization. That sounds great. It sounds like there's a lot of promise for the future of breast cancer care. Well, it's been a pleasure speaking with you. I wanted to thank you for being on our podcast today. Thank you for having me. And to our listeners, thank you for tuning into the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcasts.
Jul 24, 2019
Spanish Language Discussion of Lung Cancer Highlights From the ASCO Annual Meeting
Dr. Luis E. Raez and Dr. Gilberto Lopes review review practice changing lung cancer research presented at the ASCO Annual Meeting.
Jul 23, 2019
Dr. Priya Rastogi Discusses How the KATHERINE Study Will Inform Early Breast Cancer Care
Welcome to the ASCO Daily News podcast. I'm Lauren Davis. And joining me today is Dr. Priya Rastogi, who specializes in the diagnosis, treatment, and prevention of breast cancer at the Magee-Womens Hospital of the University of Pittsburgh Medical Center. And she's also the senior associate medical director for the NSABP Foundation. Today, we're discussing the topic of recurrence among patients with HER2 positive breast cancer, progress and providing more aggressive therapies in early breast cancer for those patients whose cancer is more likely to recur. Namely those with residual invasive disease following taxane and trastuzumab based treatment given before surgery is our area of focus. Dr. Rastogi, welcome to the podcast. Hi, Lauren, happy to discuss the exciting results from the KATHERINE study. We're glad you're here. So as an investigator of the KATHERINE study, I'd like to hear a little bit about some of the findings. So I understand that the study showed that T-DM1 reduced the risk of disease recurring by half compared with trastuzumab in HER2 positive early breast cancer. Yes. So in terms of background information, patients with HER2 positive early breast cancer receiving neoadjuvant treatment had favorable outcomes if they achieve a pathological complete response. But patients with residual breast cancer in the surgical specimen have a higher risk of recurrence. And so that's some of the rationale of how the KATHERINE study was set up. The KATHERINE trial was an open label study with 1,486 patients with HER2 positive early stage breast cancer who received neoadjuvant chemotherapy plus HER2 targeted therapy that included a taxane and trastuzumab followed by surgery. And then all these patients had residual invasive disease in the breast and/or actually in lymph nodes. So within 12 weeks of surgery, patients were assigned to either T-DM1 or to trastuzumab. And as you mentioned, the primary endpoint was IDFS. And so in the KATHERINE study, T-DM1 significantly reduced the risk of developing an invasive disease free survival event by three years by 50%. And this corresponds to an absolute improvement in three year invasive disease free survival of 11 percentage points. So this is really exciting. So the invasive disease free survival rate was 77% with trastuzumab, and it increased to 88.3% with T-DM1. So the KATHERINE trial demonstrates that neoadjuvant therapy can be used to identify patients at increased risk for recurrence based on less than optimal response to standard neoadjuvant therapies who can then benefit by switching to T-DM1. The overall survival analysis has not yet matured. We had a total of 98 deaths, 56 deaths with trastuzumab and 42 with T-DM1 for a hazard rate of 0.7. So clearly, this study will need more follow up. So the FDA approved T-DM1 as adjuvant treatment for this patient population. Do patients have immediate access? Yes, so this is also exciting news that the US FDA approved T-DM1 for the adjuvant treatment in patients with HER2 positive early stage breast cancer with residual invasive disease after neoadjuvant taxane trastuzumab based therapy. The results and approval form the foundation of a new standard of care in patients in this setting. And this should lead to access and availability for patients. Patients should discuss with their physicians and their insurance providers. That's exciting. So one of the things we always think about are side effects. What should specialists tell their patients? Yeah, so as you mentioned, side effects are very important. So the safety profile of T-DM1 is as expected from what has been seen in the metastatic setting in the use of T-DM1. The main adverse events in our study was a decrease in platelet counts, an increase in sensory neuropathy and liver enzymes compared to trastuzumab. Although, these side effects are mostly mild. Fatigue and nausea were also greater. But they were manageable and reversible. So the side effect profile is similar to what had been seen in the metastatic setting and the efficacy is fantastic for this drug. Oh, that's great. Were there any surprises in the results? So the analysis by the subgroups demonstrated that there was a benefit across all the key subgroups. So for example, patients with operable or inoperable cancers at presentation, hormone receptor positive or hormone receptor negative, post neoadjuvant positive or negative nodes, and even patients with very small residual disease all had a tremendous benefit from T-DM1. So this is also very exciting that all the subgroups benefited. So what do you think is on the horizon for breast cancer studies? That is also a very important question. So immunotherapy is a type of cancer treatment which also helps the immune system fight cancer. And immunotherapy has been approved in other cancers. One type of these drugs is atezolizumab, which belongs to a class of drugs known as the checkpoint inhibitors. By inhibiting the checkpoint proteins such as PD-L1 and PD-1, these drugs enhance the ability for the immune cells to attack cancer cells. So recently, the FDA approved atezolizumab in combination with chemotherapy for the initial treatment of women for advanced triple negative breast cancer with PD-L1 positive tumors. So the NSABP Foundation in collaboration with the German Breast Group is conducting a phase III study, it's NSABP B59 [INAUDIBLE], for patients with early stage high risk triple negative breast cancer. And so this trial is evaluating neoadjuvant chemotherapy with atezolizumab or a placebo followed by surgery. Patients then receive an additional six months of either atezo or placebo after surgery. And the co-primary end points are pathological complete response and event free survival. And this study will address if neoadjuvant atezolizumab in combination with neoadjuvant chemotherapy followed by adjuvant atezolizumab will improve outcomes in this high risk patient population. That's fantastic. It sounds like there's a lot of things to look forward to. Again, today, my guest has been Dr. Rastogi. Thank you so much for being on our podcast today. It has been a privilege. And thank you for inviting me to talk about the KATHERINE study. And to our listeners, thank you for tuning in to the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcast.
Jul 18, 2019
Spanish Language Discussion of Breast Cancer Highlights From the ASCO Annual Meeting
Dr. Mariana Chavez Mac Gregor and Dr. Henry Gomez, review practice-changing breast cancer highlights from the 2019 ASCO Annual Meeting. 
Jul 08, 2019
Spanish Language Discussion of Immunotherapy Highlights From the ASCO Annual Meeting
Dr. Gilberto Lopes and Dr. Edgardos Santos review practice changing immunotherapy research from the ASCO Annual Meeting.
Jun 24, 2019
Dr. Benjamin Maughan Highlights Key Poster Presentations in GU Cancer from ASCO's Annual Meeting
Welcome to the ASCO Daily News podcast. I'm Lauren Davis. And joining me today is Dr. Benjamin Maughan, an assistant professor in the division of medical oncology at Huntsman Cancer Institute. Dr. Maughan, welcome to the podcast. Well, thank you. It's a pleasure to be on, Lauren. It's always great to visit with you. We're glad you're here. Today, we're talking about stand out poster presentations from the ASCO annual meeting that concluded Tuesday for oncologists who are interested in prostate cancer. What did you find most interesting? You know, Lauren, there were so many great things. For oncologists interested in GU, this is such a great time. I mean, there's so much research going on. There were some wonderful plenary sessions, amazing oral abstracts and poster discussion sessions as well. But it's always riveting for me to go through the posters themselves that don't get the big splash news that a lot of those late breaking abstracts do, because there's so much great research happening that you just can't put it all in oral sessions. So there's so much great research that you can gain by going through the posters as well as well as being able to meet one on one with the principal investigators of that research. So there's quite a few things. I mean, just to start off with thinking about prostate cancer, there's a lot going on in prostate cancer research today. You know, one of the things that I found most fascinating was actually way in the back towards the end of the prostate cancer posters. Now forgive me. I wrote down the name to try and not get it wrong, but I'll probably mispronounce it. So apologies if you're listening. But Dr. Linda Huynh, I believe is how you pronounce it. The abstract number is 5085 from UC Irvine I believe is where this person works. But they were evaluating this concept of giving testosterone replacement therapy to patients with localized prostate cancer that have had a prostatectomy. So they evaluated these patients retrospectively. But they were treated, obviously, prospectively and the data was collected prospectively. But they identified 152 patients that had received a prostatectomy for localized prostate cancer and then, shortly after that, received testosterone replacement therapy to treat their hypogonadal symptoms. So then they case controlled this against 419 patients that had a prostatectomy for localized disease and did not receive testosterone replacement therapy. The primary endpoint that they were evaluating in this retrospective study was the time to PSA relapse. So interestingly, seven of the patients that had testosterone replacement therapy ultimately went on to experience biochemical relapse, so about 4% or 5% of the patients. Of those that had a prostatectomy and no testosterone replacement therapy, 39 of those patients had a PSA relapse, so about 9% or 10%. So it's a retrospective study. There's a lot of inherent biases in that. But surprisingly, the trend favored testosterone replacement therapy. Now I'm not here to say testosterone replacement therapy will help as an adjuvant treatment to protect these patients from a PSA relapse. But it's really striking and surprising. Because right now, the dogma is if you've ever had prostate cancer, then you should be very cautious or not at all ever receive testosterone replacement therapy. And they're showing that it possibly could be very safe and have a huge impact on these patients' quality of life. So that was fascinating to me. Along those lines with trying to find improvements in quality of life, there is another really interesting study that's sort of paving the way for a new paradigm of how we think about and treat prostate cancer. So Dr. Emmanuel Antonarakis from Johns Hopkins, many people may know his name as someone along with Dr. Jun Liu that helped bring to the forefront this whole new science of antigen receptor spliced variants. It sort of went off on a whole new vein of research here. I'm sorry. His abstract number is 5045, and he was evaluating in a pilot phase II study an androgen deprivation therapy sparing approach. So for the most part, as we all know, as soon as patients have relapse disease and they start systemic therapy, the bedrock or foundation of that treatment is testosterone suppression with androgen deprivation therapy. There's all kinds of side effects that are attended with that, both things that just are bothersome to the patient but significantly impacting their quality of life with hot flashes and fatigue and mental impairment and cloudiness, all the way to those asymptomatic problems that are very real and problematic, worsening of osteopenia and osteoporosis, worsening of cardiovascular disease, maybe causing dementia. Although, that is still debatable. So in this trial, he was looking at patients that had a biochemical recurrence, a PSA relapse, and was evaluating monotherapy with olaparib, a PARP inhibitor. Now interestingly, in this study, patients were not mandated to have DNA repair defects to enroll in the trial. So it was open to everybody. They were required to have a PSA doubling time that was less than six months. It turns out their PSA doubling time was, I forget the exact number, but something around the three month range. So very similar to all of these M0 CRPC studies that have come through recently, SPARTAN, et cetera. So these patients had pretty aggressive disease as defined by their PSA doubling time. So the primary endpoint was a PSA reduction of 50% or more. So this is a pilot study. So there were only 20 patients enrolled. And only three of the 20 patients met the primary endpoint, so about 15% of the patients. However, another four out of the 20 had some reduction in their PSA, anywhere from 1% to 49%. So in total, about 35% of men had a serological response of some degree. So if you actually look at the poster, though, it's pretty interesting and telling. So four out of four patients with a BRCA2 mutation responded. And of those three that I told you about that met the primary endpoint, all three of those were these BRCA2 patients. One of four patients that had ATM mutations responded. And only one of 12 patients that were biomarker negative responded. So it's really fascinating. It suggests, I mean, it clearly needs to be validated in a larger study, but it suggests that there might be a ADT sparing approach that you could do for a select group of men, which is what I hear all the time from patient advocates around prostate cancer. What do you have for me that doesn't involve testosterone suppression? So really fascinating. That sounds very promising for patients with prostate cancer. What about some other cancer types, such as bladder cancer? There was a lot of great research all the way through the GU space. So for bladder cancer, there was really two that stood out to me. They stood out to me in regards to immunotherapy. Dr. Padmanee Sharma's group at the MD Anderson Center, the abstract number is 4511, so she was evaluating neoadjuvant durvalumab and tremelimumab. So durvalumab's a PD-L1 inhibitor. And tremelimumab's an anti-CTLA-4 inhibitor. So she was evaluating this combination in a pilot phase II study in patients with muscle invasive bladder cancer but were ineligible for cisplatin. Now, that's important because right now there's no FDA-approved therapies that are proven to be effective for that group of patients either in the neoadjuvant space or in the adjuvant space. So the standard of care approach for these patients is to move forward with cystectomy or radiation therapy alone, with the majority of them getting cystectomies followed by surveillance. So their relapse rate is very high. So trying to find some other therapy that can be effective for them is a huge unmet need right now. Now, there was a couple of posters at ESMO in 2018 that suggested neoadjuvant immunotherapy can be useful for them. Pembrolizumab was tested and atezolizumab also was tested. So this was really an interesting validation to see in a separate cohort if the same approach of a PD-1/PD-L1 inhibition approach can be useful for these patients. Because this is a neoadjuvant treatment only, their duration of immune therapy was also very short. That's the other really fascinating thing to take into consideration here. So weeks 1 and 5 is when they had their immune therapy. And the planned time to surgery was somewhere between weeks 9 to 11. So far the trial isn't complete. Their planned enrollment is around 35 patients, I believe. And they're just around 30 that have enrolled. So there was a 43% complete response rate, pathologic complete response rate, at the time of cystectomy. I believe 21 patients have gone on to cystectomy in this trial, so 43%. It's really high, which is fabulous and great because the pathologic complete response rate, it's not a perfect predictor of long-term overall survival, but it's a reasonable surrogate. I mean, it's not an FDA-approved or recognized surrogate endpoint, but it correlates fairly well with overall survival for these patients. But the other reason that that number is fascinating is because if you go back and look at the pembrolizumab and the atezolizumab data, this is a fairly consistent number across all three of these trials. Anytime you talk about immune therapies, there are side effects. But it was right in line with what we see consistently with immunotherapy. So around 17% had grade 3 immune-mediated adverse events. Two patients had a delay in surgery because of complications. The delay in surgery, I should say, was reported as more than 30 days. So it can cause problems. But it's helping to create this foundation that, maybe in the future, when we get the results from my phase 3 study, it will provide some additional neoadjuvant or adjuvant therapy for these patients that are in great need. And the other one very similar to this, just briefly, was by Ronald Dewitt. And the abstract number was 4530. So this was looking at somewhat of a similar population, patients that have non-muscle invasive disease, but a refractory to BCG, which is the standard therapy today. So if you're refractory to BCG, there's some other intravesical chemotherapy you can try. The response rates aren't particularly high. Or the other option is the cystectomy. This was a much larger trial, just over 100 patients were enrolled. And they were given standard of care. Pembrolizumab was the immunotherapy in this setting. The three-month complete response rate was 40%. Of those patients that were complete responders, the median duration was very long. In fact, the median duration was around a year, I believe. And at least half of those patients that were responders had a response of over a year. Wow, that's remarkable. Yeah. So if you compare the standard of care that they'd be getting alternatively, it would be a cystectomy. So that's quite impressive. That's really exciting. How about kidney cancer? Did you see any interesting presentations? There was some great presentations on kidney cancer about clear cell disease and biomarkers coming off of the recent JAVELIN study, et cetera, that Toni Choueiri did. And other people can talk to you about that, I suppose. But in the posters, what I found particularly interesting was this focus on non-clear cell kidney cancer. So clear cell makes up the majority of kidney cancer, around 75%. But there's still this 25% that we don't have a lot of great data for. There's a couple of trials like ASPEN, et cetera, that have established TKIs as the standard of care for them. But the response duration is not great, so trying to find other therapies that have a longer duration of response is important. And so if we look at the current armamentarium of options, immunotherapy is what we look to as far as possibly providing patients a long, robust response. So there was a couple of trials looking at immune therapies with non-clear cell disease. So the first was by Michael Atkins, and the abstract number was 4569. So this was a report on KEYNOTE-427 cohort B. So KEYNOTE-427 is this two-arm trial with cohort A, or cohort one, whatever you want to call it, and is single-agent pembrolizumab in clear cell RCC. And cohort B is non-clear cell RCC. And this poster was just reporting on cohort B, the non-clear cell portion. So most of those patients-- and it was a fairly large cohort; 165 patients. Now, unfortunately, this somewhat suffers from all the research that's done for the most part in non-clear cell disease where they take all of these other histologies, they're somewhere around 8 or so, and they just lump them all together and say, you are non-clear cell disease. But we do know that they all have very distinct biology. So they fortunately did break them up at least into the top three pathologies. So 70-some percent were papillary, which is what we typically see. Of the non-clear cell histologies, that's the most common. Chromophobe was around 13%, and unclassified was around 15%. Oh, and the other important thing is they did do central pathology review, which is very important any time you're doing a non-clear cell study because the misdiagnosis rate is fairly high in this population. So these patients with any of these non-clear histologies got treated with pembrolizumab. And the overall response rate was quite high, around 24%. They specifically broke it up into those top three histologies. And the papillary objective response rate was 25%, chromophobe was around 10%, and the unclassified was over 35%. So it does show that there's a good rationale for immunotherapy in the non-clear cell histologies, at least, certainly, you could say for the unclassified and the papillary. Some people would argue that a 10% objective response rate in chromophobe isn't meaningful. There was some toxicity, as well, seen. Around 10% of patients had a grade 3-plus reaction. And this was a 165-patient trial. And six patients died directly from toxicity related to immunotherapies. So it really helps establish that immunotherapy can be useful in these non-clear cells. And that was recapitulated in a study by Dr. Rana McKay at Dana-Farber in their group there with Toni Choueiri, et cetera. And that abstract is 4583. And they looked at a similar idea with bevacizumab and atezolizumab. And this included, sort of, two cohorts, clear cell RCC with sarcomatoid features, or any non-clear cell RCC. They did not specifically break it up into the subtype of what the specific histology was for the non-clear cell group. But if you look at just that non-clear cell group of 39 patients, the objective response rate was 26%, very similar to the overall objective response rate in Dr. Atkins' study of 25%. So it's providing this promising new avenue of immunotherapy, demonstrating efficacy in this population. That's fascinating. And it's always good to look at the toxicities for sure. What else did you see this year? And did anything surprise you? As far as what surprised me or what other interesting things in the posters-- that's probably the best place, I mean, not only to meet people-- I love the posters for that-- but it's a great place to see new and developing biology of disease or understanding new technologies to monitor disease. I can't remember the abstract number off the top of my head, I apologize. But in the bladder cancer poster session, there was a poster looking at cell-free DNA. And not just presence or absence or quantity of it, but they were looking at the fraction of the cell-free DNA as a marker of patients having muscle invasive or non-muscle invasive bladder cancer. So that's just one example of many of the new, emerging uses of technology across these diseases. So it's really fascinating to see how people are thinking and using or repurposing a lot of technology for these cancers. It's a great place to go to generate ideas, I suppose, is what I'm trying to say. That's terrific. Again, today my guest has been Dr. Benjamin Maughan. Thank you for coming back to our podcast. Thank you so much. It's been a pleasure visiting with you, Lauren. And to our listeners, thanks for tuning into the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcast.
Jun 10, 2019
Dr. Nathan Pennell Highlights Key Poster Presentations in Lung Cancer from ASCO's Annual Meeting
Dr. Nathan Pennell Highlights Key Poster Presentations in Lung Cancer from ASCO's Annual Meeting.  
Jun 10, 2019
Dr. Nina Shah Highlights Key Poster Presentations in Immuno-Oncology from ASCO's Annual Meeting
Dr. Nina Shah Highlights Key Poster Presentations in Immuno-Oncology from ASCO's Annual Meeting.
Jun 10, 2019
Dr. Marina Stasenko Discusses Sexism and Bias in the Workplace
Dr. Marina Stasenko discusses the results of a survey that her team conducted which identified sexism and bias in gynecologic practices. Welcome to the ASCO Daily News Podcast. I'm Lauren Davis and joining me today is Dr. Marina Stasenko, a gynecologic oncology fellow at Memorial Sloan Kettering Cancer Center. She and her team conducted a survey of oncologists in her subspecialty to learn more about their experiences with being sexually harassed and mistreated in the workplace. Results of her study are being released during the ASCO annual meeting. Dr. Stasenko, welcome to the podcast. Thank you so much for having me today. today we're talking about sexual harassment in the workplace. Bullying, sexism, aggression, and rudeness are all common in the medical profession. One third of US women report experiencing unwanted sexual advances in their careers. What do you attribute that to? I think medicine, for many years, has really been a boys club. There have been very few women in leadership. And sexual harassment, when it did happen, just really wasn't mentioned. Over the last several decades, the face of medicine really has changed quite a bit. But I think that this study shows sexual harassment and gender biases still remain quite a pervasive problem. Was this the reason you decided to conduct a survey about this issue? Yeah. So while sexual harassment is not a new phenomenon, I think the #MeToo and the Time's Up movements have really shined a spotlight on it in areas like film and [INAUDIBLE] and even the tech industry. Unfortunately, in medicine, this discussion has really remained largely limited to private conversations. There are a few notable exceptions. But a lot of the literature that's been published really revolves around personal anecdotes. Specifically there really hasn't been a formal look at the experience of gynecologic oncologists in terms of gender disparities. So the purpose of our study was really to see what positions within our very woman focus of specialty were experiencing in regards to both gender bias disparities and discrimination. We really hope that our study adds to the growing conversation by providing a more structured look at the members of our subspecialty. I think that by identifying the problem, our study can act as a springboard for future changes. Right now, about half of practicing GYN oncologists are women. And that number is just going to continue to grow. A large portion of practicing GYN oncologists are members of the Society of GYN Oncology. This is why we've targeted our survey to the members of the SGO. We sent out an email inviting all members to fill out a short, 30-question survey. Of the roughly 1,500 members that we contacted, about 402 filled out the survey. And we actually do think that this is a good representation of our field. The responders were about 60% women and 40% men. And given the nature of the survey, we were actually very pleased with this response rate. Absolutely. The survey illustrates a big problem for women in oncology. According to the survey, why do some women not report the conduct of their colleagues when they have been mistreated? So in out study, 70% of women that responded endorsed having faced some form of sexual harassment, either during their training or while in practice. The most frequent forms of harassment were being subjected to either sexist remarks or sexual advances and receiving lower evaluations or academic positions based on gender. While most of the responders said that they were aware of work policies to report this behavior, unfortunately, fewer than 20% actually reported it. The most common reason for not reporting was that the incident just didn't seem important enough. And about 40% of respondents said this. Another third did not think anything would be done about the incident. And then, still another third were fearful of reprisal. Other less common [INAUDIBLE] thinking the issue would just resolve itself, not knowing how to report it, and then being concerned of how they would deal with a colleague once they did report the incident. What about bias in the workplace? How is this affecting people's ability to do research and care for patients? I think this is probably the crux of our study. I think there is overt ways that sexual harassment or gender biases affect women's growth. And then, there are the more covert ways. Women can be passed up for promotions or have significantly lower salaries. I think this is a conversation that's really widespread at this point. But the covert consequences are really the ones that should be mentioned. And these can include female physicians being unwilling or unable to voice their opinion in larger crowds or their expertise is just not being taken as seriously as their male colleagues. In our study, significantly more of women than men felt that gender affected their career advancement and played a role in setting their salary. But I do think it's interesting to mention that 90% of male responders felt that there was no gender pay gap in the field of GYN oncology. What do you see for women in oncology going forward? I think the future is bright. I'm hopeful that with the growing number of women in oncology and, more importantly, in leadership positions and with just a general greater awareness of the effects of sexual harassment and gender bias in our field, we will really see a culture and policy shift over the coming decade. Our final survey question was an interesting one. It was an open ended question. And we asked what changes the responders wanted to see implemented. Common themes you probably won't be surprised to hear included increasing female leadership, having open salary reporting, more transparency in hiring and promotion, more flexibility for parents, and that included both mothers and fathers, and then a general acknowledgment within our specialty that sexual harassment and gender biases do in fact exist. I do want to end on a positive note. I think it's important to mention that actually quite a few of our responders felt that our field was doing fairly well in terms of gender disparities. Because as one responder put it, women are more than holding their own. Our general hope with conducting the survey was to fuel a conversation and to fuel action within both the local GYN oncology community as well as within our specialty at large. What's our next step? Where do we go from here? I think we can take an example from emergency medicine female physicians. And there's an organization called Them in M. And this is a network that allows women in emergency medicine to engage in dialogue and explore a variety of issues regarding gender disparities. We would love to see a similar network for women in oncology, where women can really discuss these issues as they relate to work and gender and then find common strategies that can help them face challenges head on. Yes. And hopefully, some women are able to attend the Women's Networking Center during the Annual Meeting. Exactly. I think we have these key opportunities at our large annual meetings, the social network, places that we can virtually gather and physically gather to really talk about these issues as they affect us on a daily basis, as well as kind of our field as a whole and see where we can go from here. I think women in medicine, and especially women in oncology are incredibly bright, incredibly motivated, and really will change the field in an incredibly positive way. Again, today my guest has been Dr. Marina Stasenko. Thank you for being on our podcast today. Thank you so much for taking the time. And to our listeners, thank you for tuning into the ASCO Daily News Podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcast.
Jun 03, 2019
Plenary Coverage: ASCO Chief Medical Officer Dr. Richard L. Schilsky Discusses LBA4
Plenary Coverage: ASCO Chief Medical Officer Dr. Richard L. Schilsky Discusses LBA4 with Dr. Hedy Kindler. Welcome to the ASCO Daily News podcast. I'm Dr. Richard Schilsky, Senior Vice President and Chief Medical Officer of ASCO. I'm pleased to be joined by Dr. Hedy Lee Kindler, Professor of Medicine at the University of Chicago Medicine where she is Associate Vice Chair for Clinical Research in the Department of Medicine as well as Director of the Mesothelioma Program. Dr. Kindler presented abstract LBA4, olaparib as maintenance treatment following first-line platinum-based chemotherapy in patients with a germline BRCA mutation and metastatic pancreatic cancer, Phase III POLO trial during the plenary session. Dr. Kindler, welcome to the podcast. Thank you for inviting me to share the results of our study. The five-year survival rate for people with metastatic pancreatic cancer is still less than 5%. So there's a real sense of urgency to develop new treatments. The POLO trial evaluated the efficacy of maintenance treatment with olaparib, a PARP inhibitor in patients with metastatic pancreatic cancer and a germline BRCA1 and/or BRCA2 mutation. What did the study show? Well, in this study, patients with metastatic pancreatic cancer with germline BRCA1 or 2 mutations who had received at least 16 weeks of a first-line platinum-based chemotherapy were randomized 3 to 2 to olaparib tablets or a placebo. The primary endpoint was progression-free survival by blinded independent central review. This study showed that maintenance olaparib provided a statistically significant and clinically meaningful improvement in progression-free survival. The progression-free survival was 7.4 months with olaparib and 3.8 months for placebo, with a hazard ratio of 0.53 and a p-value of 0.038. Progression-free survival on olaparib was the same irrespective of whether patients had stable disease or a complete or partial response to first-line chemo. From six months onwards, more than twice the proportion of olaparib arm patients were progression-free compared with the placebo arm. 23% of patients had a response to olaparib. And what is truly remarkable is that the median duration of response to olaparib treatment in these patients with metastatic pancreatic cancer was over two years. The interim survival data at 46% maturity showed no difference between arms. And final survival results will be evaluated at 46% maturity. Health-related quality of life was preserved with olaparib treatment and showed no difference between arms. And maintenance olaparib was quite well-tolerated with an AE profile similar to that seen in other tumor types. So those are really quite exciting results. One question I had in looking at the study design is that, as you mentioned, patients in the trial all received four months of standard chemotherapy and were then randomized to continue treatment with placebo or olaparib. The question is, is it standard practice to stop active cancer treatment after four months? Would there be some rationale to adding olaparib to standard chemotherapy rather than using it as maintenance? Actually, they did not. Patients had at least 16 weeks of first-line platinum-based chemotherapy with no maximum limit to the duration. Actually, about a third of patients received more than six months of chemotherapy. This was up to the treating physician and the patient. And remember, in their cord 11 trial, the median number of cycles was 10. Continuing on folfirinox does increase cumulative toxicity, principally myelosuppression and neuropathy. So it is a very reasonable thing to want to switch to a potentially less toxic treatment. Understood. Thanks for that clarification. So you asked about whether one could combine olaparib with standard chemotherapy. Unfortunately, myelosuppression at greater than anticipated rates is the common experience of combinations of olaparib and other PARP inhibitors with chemotherapy. For example, in a phase I trial of olaparib plus gemcitabine, which had a pancreatic cancer expansion cohort, it was not possible to administer gemcitabine above a dose of 600 mg per meter squared or olaparib above a dose of 100 mg bid. So it's quite unlikely that a combination of the highly myelosuppressive, folfirinox, could be administered safely with olaparib. So if I'm understanding you correctly though, there were a proportion of patients in this study who continued chemotherapy beyond four months but also then had olaparib added during that period of time? They had chemotherapy for four months or greater and then, they stopped chemotherapy and at that point, were randomized to receive either monotherapy with olaparib or placebo. There was no combination of chemotherapy plus olaparib. Sorry, for not being able to follow this as clearly as you've laid it out. So what was the trigger to discontinue the chemotherapy then leading them to the randomization to olaparib or placebo? That was investigator and patient choice. Some patients wanted to receive only four months of chemotherapy and switch over, others wanted to continue chemotherapy for longer. Remember, there is no standard of care, particularly at the time that the study was initiated, for maintenance chemotherapy. And so, four to six months of chemotherapy, at the time of the study design, was considered a very reasonable option. Were all of the patients not progressing at the time of randomization? Correct. All patients were required to have stable or responding disease at the time of randomization. OK, so I wanted to ask you about the germline mutations in BRCA1, BRCA2. We commonly think of BRCA mutations as being associated with breast or ovarian cancer and maybe a few other cancer types, but how often is it that a patient with pancreatic cancer will be a carrier of a germline BRCA mutation? Studies have shown that between 4% and 7% of pancreatic cancer patients harbor a germline BRCA1 or 2 mutation. In view of the results of this study, now, do you feel that all patients with metastatic pancreatic cancer should be tested for a germline BRCA mutation? Well, given the treatment implications demonstrated in the POLO trial, I think it is incumbent upon oncologists to offer all pancreatic cancer patients the option of germline testing. This is supported by an ASCO provisional clinical opinion from January of 2019, which recommended that patients with pancreatic cancer undergo risk assessment for hereditary syndromes that increase pancreatic cancer risk. It states that germline genetic testing for cancer susceptibility, including testing for BRCA mutations, may be discussed with individuals diagnosed with pancreas cancer even if family history does not clearly suggest an inheritable cancer-related syndrome. Similarly, the NCCN now recommends germline testing for all patients with pancreas cancer due to data that demonstrates that germline mutations can occur at a similar rate in pancreas patients with or without a family history of any type of cancer. Thanks. So one final question for you. Given the difficulty that we've had in developing effective new treatments for pancreatic cancer patients, given the lack of effective targeted therapies, this study would seem to open up new possibilities. But as someone who's an expert in the field, what do you see as being on the horizon in pancreatic cancer research? This is an exciting trial because it's the first phase III randomized study to establish a biomarker-driven approach in the treatment of metastatic pancreas cancer. And while I hope that it will open the door to a new era of personalized care for this disease, I think we've been burned many times before. It's so common, in this disease, to see superimposable KM curves. And so, when one sees a hazard ratio of 0.53, it's genuinely exciting. But I really would not hazard a guess as to where we are going next. It's fraught with too many problems. Understood. Again, today, my guest has been Dr. Hedy Kindler of the University of Chicago Medicine. Hedy, thank you so much for being on the podcast with me. Thank you, Rich. And to our listeners, thank you for tuning into the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple podcast.
Jun 02, 2019
Plenary Coverage: ASCO Chief Medical Officer Dr. Richard L. Schilsky Discusses LBA3
Plenary Coverage: ASCO Chief Medical Officer Dr. Richard L. Schilsky Discusses LBA3 with Dr. William Tap. Welcome to the ASCO Daily News podcast. I'm Dr. Richard Schilsky, senior vice president and chief medical officer of ASCO. I'm pleased to be joined today by Dr. William Tap, a medical oncologist and chief of the sarcoma medical oncology service at Memorial Sloan Kettering Cancer Center. He presented abstract LBA3 at the plenary session reporting results of the ANNOUNCE trial, a randomized placebo controlled double blind phase three trial of doxorubicin plus olaratumab versus doxorubicin plus placebo in patients with advanced soft tissue sarcomas. Dr. Tap, welcome to the podcast. Thank you so much, Dr. Schilsky. I really appreciate the opportunity to talk to you today and also to have had the opportunity to present these data at ASCO during the plenary session. Olaratumab, a PDGFR alpha antagonist, in combination with doxorubicin was approved by the FDA in 2016 for patients with advanced soft tissue sarcomas who are not candidates for curative radiotherapy or surgery. A phase two trial showed a significant improvement in overall survival for olaratumab plus doxorubicin versus doxorubicin monotherapy. The ANNOUNCE study was designed as a phase three trial to confirm overall survival of this treatment combination. However, the study did not meet its primary endpoint. What are some possible explanations for the difference in outcomes in the phase two and phase three trials? I think that's such an important question. The results of the ANNOUNCE study have really only become available within the last few months. So therefore, at this time, there is a really large and concerted effort that is ongoing to really understand them, not only as they stand alone, but as you mentioned in the context of the phase 1B two result that led to accelerated approval. First of all, we have not found any noted discrepancies in study conduct or data integrity which could explain these findings or really discrepancies between the two studies. That's the really important initial fact. There were some notable differences between the two studies. And I know it's not great to compare two studies. But, for instance, the phase 1B two study was not blinded or did not have a placebo. It had progression free survival as a primary endpoint. There were no subtype specific analyses. And it was a relatively small study, just about 10 sites in the United States. Patients tended to be pretty healthy. But because it was just a signal finding study, many patients were coming on at later lines in therapy. There was no loading dose in the phase 1B two study. And cardio protectants, because we tended to push higher doses of doxorubicin, were used generally after patients received about 300 milligrams per meter squared. This is very different when we think about the phase three study, which again was double blinded, placebo controlled with an overall survival primary endpoint. And what's important is that this primary endpoint was a dual primary endpoint that looked at overall survival in the total soft tissue sarcoma population, but also within the leiomyosarcoma population. So we were actually looking within these two populations. And the study could have been positive if we met either of those primary endpoints. This was a large study, over 110 international sites. And it was rapidly accruing study. So there are some of these differences that are very notable. When we start to think of the differences of why we could have seen the outcomes, the first plausible explanation is that it is possible that olaratumab does not have activity in soft tissue sarcomas. But we would then have to question, why did we see such striking results within the phase 1B two trial. And it's hard to say exactly what that would have been, but it may have been to the small sample size. As you know, sarcoma really represents 50 to 80 different subtypes. And in the sarcoma community, we now look at these as potentially very different diseases with different biology. So you begin to bring in many different histologies or many different diseases into a clinical trial, and that could also explain some of the results that we saw, as these diseases often have really disparate clinical behavior. The other thing is that with an overall survival endpoint, which is a composite primary endpoint, it is possible that subsequent therapies on the phase two study may have really also affected outcomes when we looked at overall survival. We know there have been a lot of advances in many of the very specific sarcoma subtypes. And this potentially could have affected outcomes or even there could have been some chance in a smaller phase two study. The other thing that's very possible is that olaratumab has some activity in soft tissue sarcomas in general, but the outcomes were really missed in the phase three study. And this could possibly be again due to the heterogeneity of the study population, not only with the different sarcoma subtypes, as mentioned, but also within sarcoma subtypes. A disease like leiomyosarcoma can actually be a very heterogeneous disease. The other thing, as mentioned before, there could have been some differences in trial design that contributed or how the ANNOUNCE control arm did in this study. So this was not an upfront study, but still for single agent doxorubicin had one of the highest overall survival benefits for doxorubicin alone noted in any phase three clinical trial. Just to name a few final things, there were a lot of subset analyses that are being done and were done on the phase three study. It did, interestingly, point out two things. One is that patients who had a lower albumin tended to do better with the combination of olaratumab, which suggested the possibility that maybe olaratumab with doxorubicin could work better in sicker patients. And understanding this population in the phase three study seemed to be a healthier patient population in the phase two. That could have affected it. And there were some very interesting trends when we looked at PDGFR alpha signaling. And this is something that we're very interested in. And although exploratory, we're still looking very closely. But overall, PDGFR alpha positive tumors tended to do worse than PDGFR negative tumors. And there was a very interesting trend noted between PDGFR alpha positive and negative tumors that received olaratumab. There was a six month difference in overall survival noted between these populations favoring PDGFR negative tumors. So these analyses are still exploratory. And it is uncertain to the prognostic versus predictive significance of these tumors. But it's just a very interesting trend where when we're using a very selective PDGFR alpha inhibitor. Let me just follow up on that last point, Bill, which seems like a particularly important one. And it's not necessarily intuitive that the biomarker negative population seems to do better. Is it possible that PDGFR alpha is not the actual target for this drug and maybe there's a different target? We're pretty certain of the specificity of this inhibitor towards PDGFR alpha signaling, because it's a very pure monoclonal antibody. I would wonder more if there is something within mesenchymal biology regarding PDGFR signaling that we may not understand. For example, could targeting PDGFR alpha in tumors that express PDGFR alpha allow for potential up regulation of other aspects of PDGFR signaling or potentially even other signaling pathways? So one of the difficulties with soft tissue sarcoma is because it's such a heterogeneous disease, again, we may be seeing disparate biology. And because these tumors really fall into mesenchymal malignancies, we still have so much to learn about oncogenesis along mesenchymal cell lineages, and then the interplay with the tumor microenvironment and even the development of metastasis where often PDGFR or other mesenchymal signals really play a role. So where do we go from here? This drug was approved under the FDA accelerated approval pathway, as you said. That requires that post market confirmatory studies be done. The phase three trial didn't confirm the clinical benefit. And now, the sponsor has announced plans to remove the drug from the market. So first of all, what about patients who have been receiving the drug and are benefiting from it? Will they still be able to receive the drug? So fortunately, they will. As you mentioned, withdrawal is in progress. And that's important for patients and providers to know. And to me, this is the practice changing aspect of this abstract, because olaratumab did gain widespread use in almost over 40 countries. Because of these data and because we have not yet found any specific reason to explain the data, we are not recommending the initiation of olaratumab with doxorubicin in new patients with soft tissue sarcoma. But as you can imagine, many patients have been on this drug for a long period of time. And many patients and clinicians do believe that the patient is benefiting from the drugs. So this really does require informed conversations with the patient specifically regarding the data of now, and then making the decision if the patient should continue or would like to continue on that drug. And if that's the case, there is a patient access program for continuing patients. There's actually a toll free number, which is 1-833-245-8167, to gain more information about the continued use of the drug as the drug is actually withdrawn from the market. Great. That's really good to know. I'm curious to know what you think this whole experience says about the FDA accelerated approval pathway. Do you think that perhaps this drug was approved too soon? Well, I think it's a tough question for me to answer, because I'm somewhat biased, very much so regarding the unmet medical need in soft tissue sarcoma. This was the first drug that was technically approved in the upfront setting in soft tissue sarcoma for over 40 years. Normally in sarcoma, we tend to determine efficacy based on few month benefit in progression free survival. So actually having a phase two trial where we saw such tremendous improvements in overall survival for this patient population, in my mind, I think it was very important to give patients access to this drug. The other caveat to this is when we looked at the safety data between doxorubicin and placebo versus doxorubicin and olaratumab, there was very little, if any, difference regarding that safety profile. So olaratumab added very little downside to doxorubicin. So these data and the accelerated approval was really highly debated within the community. But the drug did gain widespread usage and acceptance. It wasn't unconditional. But many people really started to use the drug. I think the debate was really fueled by a smaller phase two signal, a lack of understanding potentially of the mechanisms of action, which could explain the results that we saw and also the cost, understanding that there was a significant cost with giving this drug to patients. However, being that we did not have any added toxicity, had the phase three study been positive, I would definitely have liked to allow patients in the two to three year period while we were waiting for the data of the ANNOUNCE study to have access to a potentially life improving drug as opposed to saying, we may have missed a window of a few years to get patients access to this drug. So I think the process, understanding the caveat of the data of the phase two study that I mentioned, could have really worked. The appropriate phase three study had been designed and was actually completed before FDA approval or accelerated approval was granted. So it was just a matter of waiting for that data. But I do think this is a really important topic to talk about within our community. And I also do think we should consider potentially some ways to mitigate cost for the community while we're waiting for the confirmatory results of the study to mature. So what else do you see on the horizon for treatment of patients with soft tissue sarcoma? It's clear that there's a high unmet medical need. It's a rare group of patients. As you mentioned, it's a very heterogeneous group of diagnoses and may be difficult to determine the best treatment for this heterogeneous group. Maybe patients need to be sorted. But of course, that's going to make it more challenging to recruit even smaller populations into clinical trials. But as someone who's an expert in the field, where is the field going at this point? There is a lot of hope. And I think it is still an amazing fertile ground for advancements not only in science, but also in drug development. Sarcomas really represent a major route of oncogenesis in cancer that we know very little about. We know so much more about the hematopoietic malignancies and also about the epithelioid malignancies, but very little about mesenchymal malignancies. And I think what we're seeing is a tremendous growth in our understanding of these tumors, how mesenchymal malignancies interact with tumor microenvironment and metastases. And as you mentioned, we are really beginning to also to genetically dissect out the different sarcoma subtypes. And this is yielding to some very nice advances in very specific sarcoma subtypes. So I do think as we move forward, we'll continue to see some amazing advances in single sarcoma subtypes. Examples could be diseases like tenosynovial giant cell tumors, PEComas, what we've seen in gastrointestinal stromal tumors, so a lot of hope. I do think the community is really beginning to look at these data from this and other clinical trials to say, how can we better run larger clinical trials maybe in soft tissue sarcoma in general? And is that really the right way? So there is still a tremendous amount of hope to develop drugs for patients. And really finding that right application in the right patient population is going to be critical moving forward. Bill, thanks so much. Again, today, my guest has been Dr. William Tap of Memorial Sloan Kettering Cancer Center. Thank you for being on our podcast today. Thank you so much. To our listeners, thank you for tuning in to the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcasts. Thank you.
Jun 02, 2019
Plenary Coverage: ASCO Chief Medical Officer Dr. Richard L. Schilsky Discusses LBA2
Welcome to the ASCO Daily News Podcast. I'm Dr. Richard Schilsky, senior vice president and chief medical officer of ASCO. I am pleased to be joined by Dr. Christopher Sweeney, a medical oncologist and professor of medicine at Harvard Medical School and Dana Farber Cancer Institute. He presented abstract LBA2 entitled overall survival results of a phase three randomized trial of standard of care therapy with or without enzalutamide for metastatic hormone sensitive prostate cancer, the ENZAMET trial, an ANZUP led international cooperative group trial. Dr. Sweeney, welcome to the podcast. Thank you for having me. So testosterone suppression and androgen receptor blockade, of course, have been the cornerstone of treatment for men with advanced prostate cancer for many, many years. This large trial of men with metastatic hormone sensitive prostate cancer demonstrated an overall survival advantage by substituting enzalutamide for older androgen receptor blockers. Tell us more about how the patients did on this treatment. Well, the first big line item to report is that men who got the drug enzalutamide, which, as you point out, is the more potent version of the way to block the androgen receptor than our old drugs, lived longer. In terms of relative risk, men had a 33% chance of being alive longer than men who got the older drugs. In terms of absolute numbers, 80% of men who got the early drug were alive at three years versus 72%. What's buried in all those numbers, though, is that there are different patient populations. Patients who have a higher burden disease, have a faster progression, and, unfortunately, a shorter survival than men who have a lower burden of disease. With our previous iteration of this type of a trial in men starting hormones, we showed that docetaxel benefited patients who had high volume disease very clearly. And we could also see enzalutamide works just as well with docetaxel in that patient group. On the other hand, men who had a low burden of disease, we didn't really see a benefit with chemotherapy docetaxel. But we did see a big benefit here in this study with using the hormone enzalutamide. So that now comes to the question, well, what about men who are treated with docetaxel? Did enzalutamide help them? And we actually had a group of patients in this study who we can pull out and analyze separately. And we can see that the enzalutamide delayed the time to progression when it was added to the docetaxel. But at this early analysis, we don't see any meaningful impact in survival. And that could well be because men who get the hormones and the docetaxel and then have the drugs, like enzalutamide, do just as well as getting all three drugs upfront, testosterone suppression, docetaxel, and the enzalutamide, do just as well as getting docetaxel, testosterone suppression, followed by enzalutamide. So it's a little bit of a parsing out of who the patients were and what treatments they get to work out how they actually fared. Tell us a little bit more about enzalutamide. This is a drug that's already FDA approved. It's already in use for later lines of therapy. How does it differ from the earlier group of androgen receptor blockers? Do you attribute all of the benefits seen in the enzalutamide group to the drug itself, or were there differences in patient populations perhaps from groups studied with the earlier generation of androgen receptor blockers? It seems like a pretty substantial improvement just by swapping out a newer version of an old drug. Yes, that's a very interesting observation. So the first notion is that the drug was tailored and designed by chemistry to be a much more potent version of the old drugs. So they're able to see the crystal structure of the androgen receptor and then do chemistry to say, how can we block that and shut that receptor down more efficiently? What is unique about the trial design, because we ran this as an academic study, is that we incorporated in a control arm, every patient had to have one of the older less potent drugs as a control to really show that the more potent drug did actually have all the benefits and conferred the benefits over the older drug. So it wasn't versus a non-active placebo. So it's very clear as a direct more potent versus less potent drug, we had a survival benefit. The other thing to note is that we had clues that this may work is because patients who have testosterone suppression and when their cancer progressed, they had an up regulation of the androgen receptor. So the cells say, help me, help me. I need more testosterone or testosterone like hormones to live. And it up regulates that receptor to survive. And it becomes a target that we can use. Whereas the older drugs would be able to bind to it. But sometimes, they actually became agonists. They turned the receptor on rather than turning it off. Where this drug has complete antagonistic turning the receptor off properties. So it's really quite a clear more potent drug versus less potent drug leading to the survival benefit across both patients with a poor risk, higher volume disease and a lower risk, lower volume disease. It's really interesting how understanding the structure of the androgen receptor and the chemistry of the drug really seems to have led to a very substantial improvement in patient outcomes. So this is a drug, as I mentioned earlier, that's already FDA approved, although in another line of therapy, but could potentially be substituted into routine clinical care immediately. Do you think the study results justify making that switch? It's a very important question. So another way to phrase what you just said there, Rich, is we're seeing advances in advanced stage disease. And my mantra is let's go forward by moving backwards into the earliest stage disease where the patients are starting the hormone not when they're progressing on the testosterone suppression. So when they're starting the hormones, we actually see a survival benefit when we give it upfront. That is a new indication. And so it will be up to the developer of the drug, which is both co-developed by a company called Pfizer and [INAUDIBLE], to present that to the FDA and see if it will get a label extension from the castration setting, resistance setting to the hormone sensitive setting. So that's a work in progress. Now the important item is to recognize that to be able to access the drug, there's going to have to think through the side effect profile. And there are some side effects with regard to it can cause a little bit more fatigue, a little bit more impairing concentration because of the way it works. And some patients can feel a little bit more frail. So some patients have these side effects, and there have to be dose modifications. So the risk and benefit profile has to be adjudicated. But by patients living longer and having their cancer controlled for longer, most patients do get a benefit. But the flip side is we also have to work out other alternatives. Docetaxel is an alternative for patients with high volume disease. Abiraterone is another drug that's approved in this setting, which is another different type of a hormone. And when we write for these drugs, we have to adjudicate how much the patient is going to have to pay. Some patients, they have a copay of $5. Other patients, a copay of about $2,500, because these drugs are very expensive. And if patients have no insurance, the cost is close to $9,000. So I think it is a very good option that will emerge. I suspect it will get approved. But when patients are counseled by their physicians on the options, they have to review the side effects, the benefits, as well as the financial access issues. Yeah, very important points to bring up. So it always comes down to risks, benefits, and costs, and how that translates into access. So just to wrap up, obviously, prostate cancer is a very common disease. As our population continues to age, I think we can foresee that it may become even more common in the population. What's on the horizon for prostate cancer research and treatment? This is a disease where there's been a considerable amount of progress has been made in recent years. But perhaps, there's going to be a growing medical need as the population continues to age. So where do you see the future in prostate cancer research? So the first thrust of work that I'm actively involved in and have engaged with collaborations around the globe to do more trials is to go even further back into the disease setting and augment the adjuvant therapy around the time of prostate radiation or prostate surgery to decrease the risk of relapse. So we have less patients who actually develop metastatic disease and die of the disease. So a lot of us are now getting very proactive in that setting. The other setting is profiling the tumors to work out which patients would be better treated with our current chemotherapy, be it the hormones, be it the combination, as well as develop new drugs that target new targets that are identified. So early identification and more aggressive proactive treatment to prevent relapses. And if patients do relapse, interrogate the tumors more to get more informative data on how best to treat the patient with which new drugs that emerge. So just along those lines actually, your comment prompted a thought. One of the other abstracts presented in the plenary session was about a PARP inhibitor for maintenance therapy in patients with pancreatic cancer, certainly a difficult disease to treat. There's been some preliminary evidence that PARP inhibitors may have activity in prostate cancer as well. Do you think that's going to be an emerging molecular target in prostate cancer? I definitely think it will be. And to some degree, it already is a player. What we need to do is being conducted are the proper rigorous trials to work out, which is the genomic profile that of the DNA damage repaired defects in the genes like the BRCA2 gene you're referring to, that actually do portend a potential response. So we see that the DNA damage genes, response genes that may portend a response to a PARP inhibitor are about 20%. But maybe half of those are truly the genes that really are the responders, that define the responders. And the question now is, of those particular genes that are refined, how many of those actually respond and how long? So we're seeing, I would say, responses of about 50% in that subgroup. So it is very much the notion of precision medicine, because it's the precise group of patients, which inherently is a small subset, but a subset that we can identify and potentially give a meaningful treatment with a reasonable side effect profile. So that data should emerge over the next 12 to 24 months, I think, based on the status of the trials. Great. Thanks so much for giving us that little glimpse into the future. So again, today, my guest has been Dr. Christopher Sweeney from Harvard Medical School and Dana Farber Cancer Institute. Chris, thanks so much for being on the podcast today.   It was my honor. And to our listeners, thank you for tuning into the ASCO Daily News Podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcasts
Jun 02, 2019
Plenary Coverage: ASCO Chief Medical Officer Dr. Richard L. Schilsky Discusses LBA 1
Plenary Coverage: ASCO Chief Medical Officer Dr. Richard L. Schilsky Discusses LBA1 with Dr. Amy Davidoff. Welcome to the ASCO Daily News podcast. I'm Dr. Richard Schilsky, Senior Vice President and Chief Medical Officer of ASCO. I'm pleased to be joined by Dr. Amy Davidoff, Senior Research Scientist in the Department of Health Policy and Management at the Yale School of Public Health and a member of the Yale Cancer Center to discuss racial disparities in cancer care. Dr. Davidoff presented abstract LBA1 entitled "Affordable Care Act-- Medicaid Expansion Impact on Racial Disparities in Time to Cancer Treatment" during today's plenary session. Dr. Davidoff, welcome to the podcast. Thank you for inviting me. So, obviously, the Affordable Care Act has changed the landscape for patients with cancer in many ways, including by expanding insurance coverage and improving access to care. Why did your team decide to examine the impact of the ACA through the lens of racial disparities? Prior to the ACA, low income, non-elderly adults had high rates of insurance and poor access to care, whether overall or for adults diagnosed with cancer. The population of uninsured adults was disproportionately African-American and numerous studies on the effects of the Affordable Care have demonstrated increases insurance and reduced race disparities in coverage. So we decided that we really wanted to understand whether this reduction in race disparities in coverage translated into improvements in care processes. With respect to cancer, studies by policy researchers, including myself, have demonstrated increases in insurance coverage for newly diagnosed cancer patients and some evidence of earlier stage at diagnosis for newly diagnosed cancer patients but very little research related to the Affordable Care Act in cancer patients has focused on the real processes of care. The flatiron data set allows a really rich examination of that dimension. And so we decided to examine whether there were disparities in timely treatments and whether the ACA was associated with reductions in those disparities. Makes good sense. Obviously, racial disparities in cancer care pose a serious issue and, in fact, a crisis for many patients who are at risk for either a delay in diagnosis or a delay in initiation of treatment as you point out. So tell us about your findings. How has the Medicaid expansion under the ACA improved access to care for African-American patients? Why do those patients seem to have benefited more from the Medicaid expansion than the white patients in your study population? As we all know, insurance is a really important factor in improving access to health care, generally-- specifically specialty care, such as oncology care-- and particularly for very low income adults who lack the financial needs to pay for care out of pocket. So to the extent that the ACA Medicaid expansions increased insurance coverage for African-Americans, we would expect reduced delays in diagnostic, workup, treatment initiation, continuation, and improvements in other outcome dimensions. We think that African-Americans likely benefited more than others because they had the most to gain in terms of insurance coverage. So what was the actual magnitude of benefit that you observed on your time point of time to treatment initiation? Prior to the Medicaid expansion, we measured that 43.5% of African-American patients were treated within 30 days of diagnosis and that was almost 5 percentage points less than for white patients after accounting for patient age, sex, and other factors that may have affected that timing. Patients diagnosed after their state had expanded Medicaid, among those almost 50% of African-American patients were treated within 30 days, which is now less than 1 percentage point less than for white patients. So the gap between African-American and white patients that we observed prior to Medicaid expansion had almost nearly disappeared for patients who were diagnosed in states with Medicaid expansions. So as you point out your study focused primarily on time to treatment initiation and we presume that will eventually lead to better outcomes for cancer patients. Will you be continuing to study this cohort determine if better outcomes actually were observed? We certainly can do that, particularly over time as we have longer periods in which to observe patients. We have not yet looked at that. And we certainly could for patients diagnosed in states with earlier expansions. Do you attribute the findings of your research to be due entirely to Medicaid expansion and the presumed greater access to care? Or are there other potential covariates that, perhaps, you haven't accounted for that might explain the earlier time to treatment initiation? This is something I've actually been wondering about myself is, is this strictly a result of Medicaid expansion? Or could there have been other things going on in those states at the same time or with those populations at the same time that contributed to the earlier time to treatment initiation? [? We ?] think there are a lot of things that are happening during this time period, including the introduction of many of the novel immunotherapies at end of life often that require some type of genetic testing prior to deciding about treatment. And those are happening concurrent with this sort of expanding Medicaid period that we're looking at. I think, though, that we account for those changes that are occurring over time by including control variables for quarter times, the calendar quarter. We also take into account state effects which control for sort of any unchanging underlying characteristics of each state in the analysis. So in terms of covariates, I think I'm less worried about that and more interested in other ways that the Affordable Care might have influenced timely treatment. Improving access to primary care which may have somehow assisted patients to be more informed, educated about their cancer treatment options if they had a primary care provider who is assisting them in managing those transitions. If patients were being enrolled in a clinical trial, the Affordable Care Act improves access to insurance coverage for routine care for patients in a clinical trial. So there are other aspects of the Affordable Care Act that could have facilitated these changes in timely treatment. Your point about access to primary care I find really interesting. Because in a sense, it's generally the primary care physician who makes the diagnosis of cancer. It's not the oncologist. And so when you're looking at a data set of oncologists medical records, you're looking at a population of patients who have already found their way to the oncologist. But in order to get to the oncologist, they presumably enter the health care system with a primary care provider who establishes the cancer diagnosis, gets them to the oncologist who can then initiate the treatment, which was your primary outcome measure. So there is an interesting progression here from how and when the patient can actually enter the health care system when some potential cancer related symptom initially surfaces. So it's really interesting point. I try to think holistically. In terms of this policy, I think-- not to get into politics here, but I think people who see the Affordable Care Act as just insurance coverage need to sort of step back and think about the just wide range of ways that it affects health care providers, payments, health care delivery innovation, et cetera. It's really very broad. Yes, so I was going to sort of wrap up with that question. Not to get into politics, but, obviously, the Affordable Care Act has been under threat really from the moment it was passed, maybe even before that of course from those who opposed its passage. But it is at least for the moment the law of the land. I suppose it's possible that if significant changes are made over time that states will find it more difficult to sustain this Medicaid expansion. Now, just curious as to what you're thinking about over the longer term in terms of how these benefits that are accruing to these patient populations can be sustained or what the consequences could be if the Medicaid expansion can't be continued? I think it's always hard to know how people [AUDIO OUT] when you take away something new that you've given them. So it is possible that even if some of the Medicaid expansions are rescinded that people may be motivated to obtain insurance through other mechanisms, certainly people who were eligible for Medicaid under sort of the pre-Affordable Care Act mechanisms who sort of came out of the woodwork to enroll once the Affordable Care Act was publicized and promoted. Those people probably will stay enrolled in Medicaid. But for certain populations, they were never eligible previously. And so they would probably lose their coverage. And we would go back to probably newly enhanced disparities in treatment associated with insurance, which is disproportionately affecting vulnerable populations such as African-Americans. So it's certainly something that we'll have to be alert to. And, obviously, I think your research findings in a sense illustrate the potential favorable impact of Medicaid expansion, but also expose the risks of potentially retrenching from that position. So thanks a lot for discussing your research with me. It's been really a great conversation. Again, today, my guest has been Dr. Amy Davidoff of the Yale Cancer Center. Thanks for being on our podcast. You're very welcome. And to our listeners, thank you for tuning in to the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple podcast.
Jun 02, 2019
ASCO Daily News Editor-in-Chief, Dr. John Sweetenham on Hematologic Poster Presentations To See at #ASCO19
ASCO Daily News Editor-in-Chief, Dr. John Sweetenham on Hematologic Poster Presentations To See at #ASCO19   Welcome to the ASCO Daily News podcast. I'm Lauren Davis. And joining me today is Dr. John Sweetenham, the ASCO Daily News editor-in-chief. As attendees are getting ready for the annual meeting, Dr. Sweetenham will highlight some of the poster sessions and hematologic malignancies that will capture the attention of attendees. Dr. Sweetenham, welcome to the podcast. Thank you. It's good to have the opportunity to talk. We're glad you're here. For attendees who are interested in hematologic malignancies, what areas in this specialty are you most looking forward to? So I think at ASCO this year in heme malignancies, I would characterize a lot of the studies that are being presented in poster format as confirmatory, or long-term confirmation of some earlier results. But I think they're no less interesting because of that. And I think that there is some important follow-up data, particularly in CLL, and some important confirmatory data for CAR T-cell therapy and hematologic malignancies. Added to which, I think there are a lot of potentially exciting new agents for the treatment of acute myeloid leukemia, in particular. That's been an area of a lot of interest and a lot of new treatment developments over the last two to three years. And I think that the poster sessions at ASCO this year confirm that trend is still ongoing and that the outlook for this very challenging group of patients is improving. That's great. What else can attendees expect this year? Any surprising or practice-changing data? I think, in terms of practice-changing data, I would list some of the specific abstracts which I think, as I mentioned earlier, are really confirming the importance of some agents and certainly will confirm practice changes that have happened over the last couple of years. To give you a couple of examples of that, perhaps I'll start with chronic lymphocytic leukemia. The RESONATE study was a very important study for patients with relapsed and refractory CLL, which assessed the use of ibrutinib, a once-daily Bruton's tyrosine kinase inhibitor against ofatumumab in this group of patients. The original study was published in The New England Journal, but at the meeting this year, there is mature follow up, a now six-year follow up of patients treated on this study. And the encouraging news is that the initial ibrutinib treatment, which was originally shown to produce improved overall survival, that has been confirmed. So the median duration of ibrutinib treatment on this study is now 41 months. So it really is quite extensive follow up at this point. And encouragingly, the overall survival and median progression-free survival benefits, which was 44.1 months for the ibrutinib arm versus 8.0 months for the ofatumumab arm, that has been maintained. And so it's clear that the long-term therapy with ibrutinib remains highly effective and that the number of patients who are required to discontinue ibrutinib because of adverse events is fortunately relatively low. So I think it confirms ibrutinib now across just about the entire spectrum for CLL as the important treatment, both in front line for those patients who are previously untreated, and in second and subsequent-line therapy for those who've had some other agents as the first-line treatment. I think that is very important. And along with that, there is a cautionary note from a study which explored the second cancer incidence in CLL patients receiving BTK inhibitors. Contextually, there's been quite a lot of data, over the years, exploring second malignancies in patients with CLL. In this particular study, they did actually suggest that there probably is a somewhat higher incidence of second primary neoplasms in patients who are taking ibrutinib for CLL. And those included cancers at the lung, melanoma, prostate, and bladder cancer. So I think, at this point, this is just an alert and something that we will need to watch closely as it does appear as if there is a slightly elevated risk of second cancers in these patients. And then one other follow-up study, which I think is of importance, is the fact that second-generation BTK inhibitors are now really starting to gain some traction in CLL. And there was a nice study presented in poster format which is going to explore the use of acalabrutinib, which is a second-generation BTK inhibitor, in patients who were intolerant of ibrutinib. So for those patients who need to discontinue ibrutinib because of adverse events, the second-generation acalabrutinib is effective with an overall response rate of 77% and well-tolerated so that if patients are in tolerance of ibrutinib, they certainly do have other options. I think, also, to complete the CLL field, there is a great deal of interest in the potential use of CAR T-cell therapies for CLL. And although it is very immature and the data to be presented at ASCO poster are very limited, it is just worth pointing out that there is an ongoing ZUMA-8 study for patients with relapsed and refractory CLL exploring the use of CAR T-cells. And I think that's going to be important. It will be very interesting to watch how that develops over the coming year or two. Another area which I think is very important is that we're starting to see now that there are some studies which are really exploring not only the disease-related benefits of some of these therapies, but are also starting to look at patient-reported outcomes. And there are two posters, in particular, which I think are interesting in this regard. There is one study which looked at patient-reported outcomes in patients with Waldenstrom's macroglobulinemia who were treated with ibrutinib as a single agent or in combination with rituximab. So in the iNNOVATE study, it was demonstrated that ibrutinib plus rituximab produced higher sustained hemoglobin improvements and meaningful improvements in other laboratory parameters when compared with placebo and rituximab. In this study, the investigators have gone a step further and have actually looked at patient-reported outcomes and shown that, in addition to the standard response improvements that are seen, there's a clear improvement in patient-reported outcomes associated with the use of this novel combination with ibrutinib and rituximab. And so along with the improvements in anemia, for example, there are marked improvements in fatigue-related symptoms, constitutional symptoms. And the clinical improvements are truly meaningful. And that's actually mirrored in a different context, but in patients with multiple myeloma who were previously undiagnosed and treated with a novel combination of daratumumab, lenalidomide, and dexamethasone versus the same regimen but without the daratumumab. And here, again, there is important patient-reported outcomes demonstrating that, essentially, with the novel combination, patients feel better more quickly. So the clinical responses that have been demonstrated on that trial are confirmed by patient-reported outcomes, which demonstrate that patients are truly feeling better. So, again, I think at the patient level, these are very important data. Some other things that I think are important to look out for at this year's meeting, there are a series of posters which explore novel therapies for acute myeloid leukemia and myelodysplastic syndrome. Without listing these in great detail because there are several of them, I would simply say that these studies add to the extraordinary expansion of available treatment options for patients with AML that we've seen developing over the last few years. And I think that the treatment landscape for these patients is really changing now. Sequencing prior to therapy is becoming important as more novel targets are identified, but consistent with the trend we've seen in the last two or three years, more important emerging therapies for patients with acute myeloid leukemia. Shifting gears for just one moment and looking at patients with B-cell lymphoma, and specifically aggressive non-Hodgkin lymphomas, I think that there are a couple of studies here which show promise, although certainly I wouldn't categorize them right now as being practice changing, but the findings are interesting. One of those is, again, in the context of CAR T-cell therapy. So it's difficult to talk about heme malignancies at the moment and not talk about CAR T-cells because there's such a lot of buzz and excitement around those. And one of the areas where this intervention is now FDA approved is in the treatment of patients with relapsed, aggressive non-Hodgkin lymphoma, particularly diffuse large B-cell lymphoma. And that was the subject of the so-called ZUMA-1 study, which was a phase 1/2 study of axicabtagene ciloleucel in patients with refractory large B-cell lymphoma. The study reported out some months ago now, but one of the concerns that some of us have had is that this may be a very reasonable treatment for the young patients with a good performance status who typically don't represent the bulk of patients with large B-cell lymphoma. But what about those patients who are older? And how do they tolerate this therapy? And what's the outcome? And in a study that's going to be reported at ASCO this year, the investigators of the ZUMA-1 study conducted a specific subset analysis on that group of patients who were aged 65 years or older. It's a small group. But I think the take-home message from the study is that the outcomes in this group, in terms of the overall response, complete response, and overall survival rates are very comparable to the younger age group. And the toxicities are very comparable to the younger age group, as well. So I think this is important that age, in itself, may not be a barrier to the applicability of CAR T-cell therapy. And that's a very important message. The flip side of that is that these one, it seems a pretty highly selected group of patients aged 65 years or older. And certainly, that's reflected in the performance status and the IPI scores of these patients as reported in the abstract. So they may be a highly selected group of patients aged 65 or over with this disease, but nevertheless, I think they're quite compelling results. And I think it speaks to the broader applicability of this therapy in patients with relapsed, aggressive lymphoma. The big remaining question being, how are patients and perhaps, more importantly, how is the health system, as a whole, going to cope with the cost and the financial toxicity associated with this very important new treatment? Again, on the subject of aggressive B-cell lymphoma, there is one more study which caught my eye. And it's interesting for a couple of reasons. This is a study which explores the use of a PD-L1 inhibitor, durvalumab, alongside either the R-CHOP regimen or the R2-CHOP regimen in patients with newly diagnosed high-risk diffuse large B-cell lymphoma. And this includes patients with double-hit lymphoma where we know the prognosis is particularly bad. These are very preliminary data in which a standard therapy with R-CHOP or R2-CHOP is being modified by the addition of this anti-PD-L1 monoclonal antibody. At the moment, the data are very largely related to adverse events. And there are some very preliminary outcome data, but probably difficult to read anything very much into those. The interest, to my mind, is that some recently-published data have suggested that checkpoint inhibitors in aggressive B-cell lymphoma may not be a particularly effective treatment modality. But I think it will be very interesting to see whether the combination of checkpoint inhibitors plus regular chemotherapy have the opportunity to improve outcome. So I think this is a study in progress. It's way too early to draw any conclusions at the moment. But I do think it's important not to write-off the role of checkpoint inhibitors in aggressive lymphomas without conducting important studies like this one which look at combination therapies rather than just the single-agent therapy. And then, in conclusion, one other study which I think is quite important, again, presented in poster form, and this was a study that looked at survival disparities of diffuse large B-cell lymphoma in a community-based cancer center. And essentially, this was a retrospective study which looked at 381 patients who had aggressive lymphomas and looked at outcome according to race and showed very highly significant disparity in survival for those patients who were African American where their overall survival was markedly inferior to other patients with a hazard ratio of 2.19. So it was a really very marked difference in outcome. The explanation for this is not entirely clear from the abstracts. But I think it's something which is very important for us to take note of. So that is just a quick run-through some of the poster presentations that caught my eye at the meeting this year. I think that there will be some important practice-changing studies presented during the oral presentations. And I would certainly strongly encourage folks to be at those. But I think that, as always, there are some important highlights in the poster presentations. And I could go on with many more, but I think that those probably be the highlights from my perspective. Sounds like some promising studies to look forward to. Again, today my guest has been Dr. John Sweetenham. Thank you for being on our podcast today. Thank you. Great to have the opportunity to talk. And to our listeners, thank you for tuning into the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple podcast.
May 15, 2019
Preserving a Future Family: Dr. Mary Lopresti on Oncofertility
Mary Lopresti, DO, is a hematologist oncologist with the Lifespan Cancer Institute, where she treats patients who have breast and gynecologic cancers. Most of her patients are younger than 42 years.  Welcome to the ASCO Daily News podcast. I'm Lauren Davis. And joining me today is Dr. Mary Lopresti, a hematologist/oncologist with the Lifespan Cancer Institute, where she treats patients who have breast and gynecologic cancers. Most of her patients are younger than 42 years. Dr. Lopresti, welcome to the podcast. Oh, thank you so much, Lauren, for having me today. We're glad you're here. Today we're talking about issues around fertility and how cancer can present challenges to women who want to be able to get pregnant and grow their families. Because you treat younger patients, at what point in the diagnosis process do you mention fertility options such as egg freezing? Well, we've made it our practice at Lifespan to discuss this at the first touch point with the patient. So our young women who are newly diagnosed with breast cancer will come in to a multidisciplinary clinic, and so they'll need a breast surgeon, medical oncologist, radiation oncologist. And besides from talking about their new diagnosis and management, at that point, we'll also ask them if they plan on growing their family or having another baby or a baby. And at that point, we'll ask them if they would desire fertility preservation. And so we really from day 1 of meeting them will explore that option. What are some of the struggles in helping patients navigate cancer care when they also have to decide whether or not they want to preserve their fertility? I think this biggest struggle is timing, trying to help this woman decide on her breast surgical options, discuss genetic testing. And many of these young women have aggressive breast cancers requiring chemotherapy, so it's the timing of when we give the chemotherapy. And then if we are planning to give chemotherapy, how does fertility fit in? Many times, I think physicians shy away from mentioning fertility because there's a delay in chemotherapy, which is so important. And so we've tried to get that timing down a little bit better by developing an algorithm to get that woman to a fertility specialized in a streamlined manner, and that has helped us navigate these young women a little bit better. What advice do you have for physicians who ideally would mention fertility preservation but sometimes leave it out because of the patient's need to start treatment such as chemotherapy as you mentioned immediately? Well, I think that it's very understandable for an oncologist to feel like they need to leave it out if a young woman has large tumor burden and they're very worried about starting systemic therapy. But yet, I think it's really up to us as physicians to make sure that the patient has informed consent. And ASCO has published guidelines for preservation so that we can help educate our patients on what options that they have. And I think we need to continue to try to do that and put our own worries aside. Are there patients for whom you do not recommend fertility preservation? And how do those conversations go? I'd say in general, no. I think we offer it to anyone who desires to have a pregnancy in the future. Again, there's always a worry in a woman who has an estrogen positive breast cancer, a large tumor, bulky lymph node disease to recommend fertility preservation because the concern has generally been that you could stimulate very high levels of circulating estradiol level with preservation. But now with letrozole, which is an aromatase inhibitor, and tamoxifen, there are ways to decrease the estradiol level and still get mature follicles as well. So I think that we do recommend fertility preservation everyone. And then just moreover on that point is that there was a recent study by Rodriguez-Wallberg and colleagues. It was a Swedish match cohort trial. And so they looked at women undergoing fertility preservation compared it to age match controls, and there was not an increase in the risk of recurrence with fertility preservation. So it's a generally safe and can be done in about a two-week period. That's wonderful. What do you see for the future of cancer care in oncofertility? I think our knowledge will continue to increase as newer drugs come on the market. I think we should all be concerned about fertility because we're not going to know how they affect fertility in the mechanisms there. So I think as physicians, we have to become more educated, and I think we're going to see more physicians talking to their patients. I think we're going to see more patients having access to educational materials or looking on social media for decision trees to help them with fertility preservation. I think we're going to know more about other methods of fertility preservation like ovarian tissue retrieval, which has been largely experimental, but there has been more and more done with that. And then there's pre-implantation genetic testing which is being done. And we're going to be hearing more about that in the future as well. That's exciting. Again, today my guest has been Dr. Mary Lopresti. Thank you for being on our podcast today. Thank you. And to our listeners, thank you for tuning in to the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and reviews on Apple Podcast.
Apr 11, 2019
Dr. Marco Davila Discusses How CAR T-Cell Therapies in B-Cell Malignancies Show Promise for Other Cancers
Dr. Marco Davila Discusses How CAR T-Cell Therapies in B-Cell Malignancies Show Promise for Other Cancers.    I'm Lauren Davis. And joining me today is Dr. Marco Davila a medical oncologist in the Department of Blood and Marrow Transplantation and Cellular Immunotherapy at Moffitt Cancer Center. His clinical focus is utilizing cell therapies to treat patients with hematologic malignancies. Dr. Davila, welcome to the podcast. Thanks so much for the invitation. Today we're talking about CAR-T therapies and B-cell malignancies. Your work with targeted therapies in leukemias and lymphomas has grant great promise for patients who, historically, we would not expect to have seen such sustained responses. What do you attribute these response rates to? Well, this is really a tremendously novel therapy. These patients that have been approved for this therapy have been deemed to be chemotherapy refractory, meaning kind of the standard treatments that you'd give these patients, the patients' malignancies have become well adapted to or are able to evade the treatments. So the immunotherapies that are being applied for these B-cell leukemias and lymphomas really are a complete paradigm shift for medical oncology as well as for the patient's cancers. So these patients' cancers, while they've been well-adapted to chemotherapies, they have not been adapted so well to CAR T-cell therapy. Can you walk me through the process of obtaining these therapies? What's the general timeline? Sure, so the first thing we have to do as a medical oncologist is determine that the patient is eligible for the CAR T-cell therapy, if they meet the indications in the label provided by the FDA and the drug manufacturer. So that involves mainly making sure that they have the diagnosis of an aggressive B-cell lymphoma and/or a B-cell acute lymphoblastic leukemia that has relapsed and received at least one prior therapy. So once we deem that the patient is eligible for therapy, we then arrange for the patient's peripheral blood mononuclear cells, and more specifically, T-cells, be isolated from their blood. So this involves a apheresis procedure, where the patient comes in, usually has the large-bore needle inserted in one arm to collect the blood. It goes through a machine, filters out the cells, and returns the blood through another large-bore [INAUDIBLE] needle in the patient's other arm. So this procedure can last several hours. But afterwards, billions of cells are sent to the manufacturer for isolation of T-cells, and then genetic retargeting to the CD19 antigen present on the patient's B-cells, malignant B-cells. Amazing-- what other cancers can be targets in the future? So the initial approvals, as I said, have been for B-cell acute lymphoblastic leukemia and aggressive B-cell lymphoma, but there is very promising late-stage data targeting multiple myeloma, targeting the B-Cell Maturation Antigen, BCMA. And I think many of us expect that myeloma will get an approval for this treatment with BCMA-targeted CAR T-cells sometime in the next year or so. And that's going to really represent another kind of big change to a medical oncology and bone marrow transplantation programs throughout the US. And that's because two of the major indications for autologous stem cell transplantation, so auto stem cell transplants, are aggressive B-cell lymphomas and myelomas. So many of these patients that standardly would receive an autologous stem cell transplantation may in fact be candidates for CAR T-cell therapy instead. So while myeloma is next in line, I think there's a lot of interest in adopting this technology later to, or hopefully shortly to acute myeloid leukemia as well. What are some of the obstacles in applying this technology at a cancer center? Well, I think probably one of the biggest obstacles is that there is a time of production, a time of [? TCQA ?] analysis to make sure that the product that's been made is safe, is not contaminated or anything like that. And sometimes the production time and the [? TCQA ?] time could be short, maybe about two to three weeks. Sometimes this lasts longer than a month. And as I said earlier, in terms of the indications for this therapy, aggressive B-cell leukemias and lymphomas that are chemotherapy refractory, that these are patients that can't necessarily wait months for a product. So that I think is probably the biggest challenge, to be able to see a patient in the clinic and go, yes, you have very bad aggressive leukemia and lymphoma. And you meet this indication for this therapy. So we're going to collect the cells. And you know, we'll see you sometime in a few weeks or in a few months when the product is ready. That's probably the biggest challenge. I think, luckily, for some of these products, it seems that their production times have been relatively reasonable, maybe two to three weeks. Other kind of products have really unfortunately taken longer than a month. And those are probably one of the reasons that some of these products are favored by medical oncologists right now, because of disparate in production times. So it kind of has meant that, for some of these patients, we have to kind of keep them in the hospital to give them a bridging therapy, meaning that we try to keep their disease kind of quiet until their cells are ready. So that's probably been the biggest obstacle. Of course, there is a financial obstacle. There is toxicity obstacles. You know, these CAR T-cell therapies are associated with a unique set of inflammatory or immune-related toxicities and neurologic toxicities, so we've had kind of, as a group of investigators, develop diagnostic and grading schemes and management schemes to manage these toxicities. And I think overall, the last few years, we've seen a lot of progress in this area. And overall, the therapy has become safer than it was maybe 10 years ago when we started developing the first clinical trials for patients with B-cell leukemias and lymphomas. So in terms of growth, how quickly can this adapt from, say, 20 to 30 cancer centers to other hospitals? Well, I mean, I think that's the huge need, is that we need this technology be applied at multiple centers. At the center that I'm located at, we are a major CAR T-cell therapy center for probably the Southeast, and really, in the world. We have patients from other countries that come to my institution to get this therapy because it hasn't yet been improved that their own country. But it means that we're starting to kind of reach our own capacity to be able to provide standard of care, as well to provide know experimental cell therapies, to try to begin pushing the envelope. What's the next disease that we can use to target with these novel T-cell therapies? That means that, for us to be able to do these innovative clinical trials, we need other institutions to be able to kind of shoulder the standard of care. So right now, there is probably about 30 sites that are providing this technology across the US. Probably the vast majority of these cell therapies really are probably given by only 10 centers. So there is a really big need to be able to go from 30, to really, close to 100 centers in the US need to be providing this therapy for patients to be able to be located close to these sites, for providers to be able to kind of start learning about this technology as well. And I think probably the big obstacle for that is just kind of just somewhat of the infrastructure that's required to be able to provide this therapy. So institutions have to be able to have a [? FACT-accredited ?] clinical site, where they are approved to be able to collect cells, to be able ship cells, to be of a process these cells for infusion into patients. They have to be able to have multiple doses of tocilizumab, for example, to be able to manage the toxicities. They have to go through kind of an onboarding and auditing process by the manufacturers of these technologies, because it's given under a REMS program, a Risk Evaluation Mitigation Strategy mandated by the FDA. So there is a lot of hoops that these centers have to be able to go through to provide the therapy. And I think that many of them are, but it's just taking them-- they're the second or third big groups that are going to be getting their approval to be able to provide this therapy. But I think that it's a need for patients. It's a need for the primary centers that are providing this technology right now, is to have collaborators to be able to do this. And as I said earlier, one of I think the biggest pushes that we've had for developing these kind of harmonized toxicity grading schemes, and diagnostics schemes, and management schemes, is to be able to provide this to new CAR T-cell clinicians to be able to say, this is the path you should follow in terms of managing or infusing and managing these therapies. That brings me to my next question. And you just mentioned toxicities. What kind do you expect? And how do you manage them? There is two well-characterized toxicities now associated with CAR T-cells. And there is the third as well that I want to mention that I think now is being a little more appreciated. The first is the Cytokine Release Syndrome, or CRS. And this is essentially a constellation of symptoms that is associated with cardiovascular and pulmonary kind of toxicities. So patients can be hypoxic, tachycardic, hypotensive, any of these number of symptoms. And really, the hallmark of the CRS bill is a high-grade fever that can occur as early as the night of infusion. And what's believed to be the mechanism behind this toxicity is the in-mass activation of CAR T-cells by their antigen. And with these CAR T-cells get activated, they secrete cytokines and then activate other immune cells that then can get activated and secrete other cytokines, and kind of create this rapidly escalating inflammatory kind of syndrome. And so we and the other CAR T-cell investigators across the US and the world have developed diagnostic and grading schemes to be able to classify CRS. And while maybe 10 years ago, the standard of management of CRS was really kind of trying to withhold therapy until-- there was concern that the patient was at high risk of death, over the last few years, we moved an early intervention program, where we really kind of intervene at grade two levels of CRS, whereas maybe 10 years ago, it was grade four CRS. And I think that had a really huge impact at making the technology much safer. The concern was that, by intervening, you may be impacting the efficacy of the CAR T-cells, but luckily, that has not borne true. The second major toxicity is considered to be a neurologic toxicity. So these are, again, another constellation of symptoms that can range from mild kind of confusion, difficulty speaking, to sometimes grand mal seizures and the patients completely obtunded to the point where that they need to be intubated to protect their airway. And this one, while there is, I think, again, a good uniform harmonization of the way we grade these neurologic toxicities, in the way we intervene them, there is still not a great understanding of what's the mechanism behind this toxicity. So our interventions really rely only mostly on steroids. And some of course will get tocilizumab as well. But we're not certain if how well these agents are at actually mitigating some of these toxicities, or not certain how to treat neurologic toxicity also in the setting of a patient with cytokine release syndromes. There is guidelines, but we're not certain in terms of how effective those guidelines are, probably because we don't necessarily have objective markers to follow with neurologic toxicity. So I think that's a huge area of need right now for CAR T-cell research. And the last one that we're starting to learn about, at least, again, based on the FDA-approved therapies, is B-cell aplasia. Since this CD19 antigen that's been targeted on malignant B-cells is also expressed on normal B cells, that means patients' normal B-cells will be killed by this therapy as well. So you can have patients that have six months, nine months after treatment, or sometimes years after treatment that, when you check their peripheral blood or their bone marrow, they actually have no B-cells. And they have very, very low gamma goblin levels, which are the antibodies that are secreted by B-cells, and that these patients can be prone to developing infections. And so I've seen a few patients in my own clinical experience coming back to the hospital six months, a year later with these recurrent infections. Then, lo and behold, it turned out that they have hypogammaglobulinemia. They have B-cell aplasia, that these patients that required longer course of antibiotics, and potentially IVIG to help kind of support them through these periods of infections. And that's something that really has to be kind of-- what I'm working on is trying to make sure that this is communicated well to the primary medical oncologist, because those are the patients that are really going to be following the patient's long term. So most of these CAR T-cell centers evaluate the patient, and treat the patient, and kind of get the patient through that first month or so after CAR T-cell infusion. But it's ultimately the patient's primary medical oncologist that is going to be managing the patient long term, and it's going to be likely then that's going to be managing the complications of B-cell aplasia long term. How about clinical trials? Are there any trials that are looking towards the future to move the field forward? Absolutely, so there are trials, as I said before, targeting AML. There is NKG2D-based CAR technology that already been part of a report that's shown patients with objective responses with this therapy. So we're really excited about that technology. There is also TCR-based gene therapy as well, going on for multiple different solid-tumor malignancies. There are CARs that are being clinically evaluated for glioblastoma multiforme. And there are also CAR-T developed for any number of other malignancies, such as mesothelioma, prostate cancer. So these are all things that are in the clinical pipeline already there. And there is a next iteration of technologies where, really what we're seeing is the clinical application of the technologies that were developed probably 5 or 10 years ago. But there is a whole new pipeline of exciting innovations or refinements of CAR T-cells, so bringing in a kind of third generation or armored CAR design, where you add in a cytokine secreting element to it, or where you have a molecular switch so that you can finally control the expression of the CAR or the downregulation of the CAR for safety issues. So these are things that I imagine are going to reach the clinic in the next year or two. And there is a lot of excitement for it, because that's going to really add to our CAR toolkit for the future, to be able to make this technology more efficacious, but also more safe. That's fantastic. Again, my guest today has been Dr. Marco Davila of Moffitt Cancer Center. Thank you so much for being on our podcast. My pleasure. And to our listeners, thank you for tuning in to the ASCO Daily News Podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcast.
Mar 21, 2019
Key Takeaways from the ASCO-SITC Clinical Immuno-Oncology with Dr. Steven Eric Finkelstein
Key Takeaways from the ASCO-SITC Clinical Immuno-Oncology with Dr. Steven Eric Finkelstein. Welcome to the "ASCO Daily News podcast." I'm Lauren Davis and joining me today is the "Immuno-oncology Daily News" Associate Editor, Dr. Steven Eric Finkelstein with Florida Cancer Affiliates the US Oncology Network. Dr. Finkelstein, welcome to the podcast. Thank you so much for having me. The Immuno-oncology Symposium just concluded on Sunday. How was this event compared to last year's? Well, this year's event was, again, extremely exciting. This year's event featured research and discussion surrounding themes of patient-centered rational steps to move the field of immuno-oncology towards the future. Now, as many of us know, immuno-oncology has dramatically altered the treatment landscape for many malignancies, and this progress has been extremely rapid over the last decade. As the field has progressed, researchers and clinicians are pushing it towards a better understanding of how immunotherapy can affect patients and the best and most rational combination approaches can improve responses and long-term outcomes. What presentations stood out to you? Another exciting area of research was that the combination of lenvatinib and pembro yielded promising antitumor activity and progression-free survival in patients with metastatic urothelial carcinoma. In abstract 11, a Phase Ib/II study was reported. And as we know, urothelial cancer can account for 90% of all bladder cancers. Pembro monotherapy is currently approved as a first-line therapy in patients who are ineligible to receive cisplatin or platinum-based chemotherapy. It's also approved as a second-line treatment for patients with advanced or metastatic urothelial cancer. Lenvatinib, a multikinase inhibitor, a VEGFR-1 through 3, FGFR-1 through 4, PDGFR-alpha, RET, and KIT is used as a single agent in several malignancies, including thyroid cancer and hepatocellular cancer. Dr. Vogelzang, who presented the results of the study, discussed the Phase II portion of the study, which included 20 patients with histologically confirmed metastatic urothelial carcinoma. The primary outcome in the trial was immune-related resist objective response at 24 weeks. Five patients achieved such a response for an overall response rate at 24 weeks of 25%. Dr. Vogelzang's conclusion was that lenvatinib plus pembro demonstrated promising antitumor activity with manageable adverse events. The response rate warranted further investigation and lenvatinib plus pembro combination will be studied in a Phase III trial in urothelial carcinoma. What other research were you interested in? A Phase Ia/Ib trial was launched in order to evaluate the safety of LY3321367, an anti-T cell immunoglobulin-domain and mucin-domain containing molecule 3, or TIM-3 antibody. Administered alone or in combination to LY3300054, which is an antiprogrammed death ligand, or PD-L1 antibody in patients with advanced, relapsed, or refractory solid tumors. An analysis of the trial that was presented by Harding at the meeting in Abstract 12. This focused on the safety, efficacy, pharmacokinetics, and pharmodynamic results seen with these treatment regimens. The key points are as follows-- treatment-related adverse reactions were mild, i.e. Grade two or less, in both treatment groups except for one patient with a Grade three anemia in Arm B. No dose-limiting toxicities, dose-limiting equivalent toxicities, treatment-related serious adverse events, or death was observed in either treatment arm. Approximately 68% in Arm A and 88% in Arm B of patients were positive for treatment emergent antidrug antibodies related to the LY3321367. Despite antidrug antibodies, there was no effect on pharmacokinetics noted That's great. Were there any education sessions that caught your attention? I think at the 2019 ASCO SITC Clinical Immuno-Oncology Symposium, what really struck me were the keynote addresses. On March 2, the keynote lecture from Dr. Rafi Ahmed of Emory University examined the basic scientific underpinnings of the field and focused deeply on T cell exhaustion and differentiation. In a second keynote address, Dr. Jedd Wolchok, of Memorial Sloan Kettering, took a broader look of the future of immunotherapy. And his main thesis was there was a need for a more rational approach to combination therapies. Indeed, it is apparent that the combination of therapies will be an important role for our future. That's wonderful. Were there any other takeaways that were important during the symposium? ASCO and the Society of Immunotherapy of Cancer, SITC, have really focused on developing recommendations for clinical trial reporting. Indeed, we need trial reporting that addresses the unique efficacy, toxicity, combination, and sequencing aspects of immuno-oncology treatments. As many know, ASCO and SITC had convened a working group that consisted of medical oncologists, immunologists, clinical research, biostatisticians, and representatives from industry and government to develop important recommendations, also known as Trial Reporting in Immuno-oncology, or TRIO recommendations. The recommendations based on expert consensus are important given that existing data to support evidence-based recommendations are limited. The recommendations given by TRIO are intended to improve the reporting of IO clinical trials and thus, provide more complete evidence on the relative benefits and risks of immuno-oncology. Given the rapid expansion of the number of IO clinical trials and ongoing improvements to evidence base using IO treatments and clinical care, it is apparent that these recommendations will likely need regular revision. And the annual meeting of ASCO and SITC will be an important place for TRIO recommendations to continually be updated. Thank you. Again, today, my guest has been Dr. Steven Eric Finkelstein. Thank you so much for being on our podcast today. It's been an absolute pleasure. Thank you so much. And to our listeners, thank you for tuning into the "ASCO Daily News" podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcast.
Mar 07, 2019
Dr. Benjamin Maughan Discusses GU Cancer Symposium Takeaways
Dr. Benjamin Maughan who is the mentee of the GU Daily News Associate Editor, Dr. Neeraj Agarwal, discussed the presentations and research that stood out to him during the recent GU Cancer Symposium. Dr. Maughan is an Assistant Professor in the Division of Medical Oncology at Huntsman Cancer Institute. Welcome to the ASCO Daily News podcast. I'm Lauren Davis, and joining me today is Dr. Benjamin Maughan, who he was the mentee of the GU Daily News Associate Editor, Dr. Neeraj Agarwal. Dr. Maughan is an assistant professor in the Division of Medical Oncology at Huntsman Cancer Institute. Dr. Maughan, welcome to the podcast. Well, thank you. It's a pleasure to speak with you, Lauren. So you've just returned from the GU Cancer Symposium. How was this year's event compared with previous years? It was fantastic. Lauren, I've been going to GU ASCO for a number of years now since I was starting fellowship at Hopkins, and it just keeps getting bigger and bigger. So it's a fabulous meeting. One significant change, I will say, this year compared to the previous year is, as the meeting is getting bigger and there's a lot of research going on in the GU malignancies, we're starting to see more and more practice-changing results and research being presented at GU ASCO. That's very exciting. What presentations stood out to you? There, actually, were quite a few, as I was alluding to with your previous question. But definitely the practice-changing data really stands out the most. And we saw that both in the field of prostate cancer and kidney cancer. I guess specifically in the prostate cancer, we saw a number of trials that have been published to date exploring in this M0CRPC space, or patients who have castration-resistant prostate cancer but no identifiable metastases on scans since M0CRPC. We've seen a couple of these trials with PROSPER and SPARTAN showing that apalutamide and enzalutamide respectively improved metastasis-free survival in this setting. Now, at GU ASCO 2019, we saw the third big trial presented, which was darolutamide with the ARAMIS trial. This, again, was in an M0CRPC patient population, and they were randomized 2-to-1 to darolutamide or a placebo. Of note, the baseline characteristics were pretty similar to what we've seen with the PROSPER and SPARTAN trial, in that the PSA doubling time was pretty short, meaning these were fairly aggressive patients. That's an important point because some patients have a very prolonged PSA doubling time, and those patients may not benefit from any of these therapy. Those specific trials have not been done. So it's unclear the value of these therapies in those better prognostication patients. But regardless, in the ARAMIS trial, we saw a significant improvement in the primary endpoint, which was metastasis-free survival. It was 40 months with darolutamide versus 18 months with a placebo, and led to a significant improvement as measured by the hazard ratio and it was statistically significant. Interestingly, all of the other specific subgroups appeared to benefit-- age, prior [INAUDIBLE] therapy, radiation, or surgery. So now we have a lot of data between all three of these trials showing that novel hormonal therapies with either apalutamide, enzalutamide, or now darolutamide significantly benefited these patients. Now, because these patients have no metastases, we always have to ask our question-- and therefore, they're not having any symptoms from their disease-- we have to be very cognizant of any specific side effects that we may cause or a worsening of their quality of life by introducing therapy this early in their treatment process. And that was really encouraging news with the darolutamide. The discontinuation rate of darolutamide was the same as the placebo group, 8.9% and 8.7% respectively. Fatigue is a big issue with this patient population because of their ADT therapy, which causes a lot of fatigue. We've seen fatigue with apalutamide and enzalutamide. And there was a slight increased rate of fatigue or asthenia in the darolutamide compared to the placebo, but it was small-- it was around 15% or 16% versus something like 11% with placebo. So it appears that it's very well-tolerated. So that was really encouraging news overall. The other big news with prostate cancer was in a slightly different space, it was in the metastatic hormone-sensitive prostate cancer population. And this was the ARCHES trial, specifically with enzalutamide versus placebo. So in this trial, patients were randomized one-to-one to either ADT with placebo or ADT with enzalutamide. Now, historically for these patients, the treatment-- we've seen a number of clinical trials looking at ADT plus chemotherapy or ADT plus abiraterone, both showing improvement over ADT plus placebo alone. And so this trial, we've been anticipating for a while. Again, it showed that patients regardless of high volume or low volume disease, if they had de novo metastatic disease, so they were presenting with metastatic disease at presentation of their diagnosis of prostate cancer or if they had previously been treated for localized disease and then progressed to metastatic disease, all of those patients appeared to benefit with the addition of enzalutamide over placebo. Very importantly, though, a number of these patients, just because of the CHAARTED and the STAMPEDE data that came out before, a number of these patients were allowed to receive docetaxel before enrolling in this trial. Somewhere around 20% of the patients had received prior docetaxel, and those patients also appeared to benefit from the enzalutamide. And that's particularly important because now we're starting to ask the question, since docetaxel and these novel hormonal therapies have non-overlapping toxicities and distinct mechanisms of action, what about trimodality therapy? So again, it's a relatively small subset, only about 20% of the patients, but it's intriguing and interesting to note that they also did benefit. So now in the prostate cancer realm at GU ASCO 2019, we saw further evidence that the M0CRPC population benefits from darolutamide. We saw that in the ARCHES trial, enzalutamide is another therapy that appears to be highly effective in these patients with metastatic hormone-sensitive prostate cancer patients. And so all of that was very encouraging news. That's very exciting in the research front. What about the education sessions? Were there any that caught your attention? Yes. So in terms of the educational sessions-- again, that's one of the nice features about some of these disease specific symposia, as opposed to the annual ASCO meeting, is there's a lot of education, as well as just straight research. And so we get lots of debates about controversial topics with a lot of thought leaders in the field, et cetera. So that's another nice part of GU ASCO. One debate or educational session that I thought was very interesting was this discussion between a radiation oncologist, [? Jason ?] [INAUDIBLE], and a urologic oncologist, Michael Cookson, about what's the ideal first line therapy for patients with muscle-invasive localized bladder cancer. Is it trimodality therapy or is it neoadjuvant chemotherapy followed by cystectomy? This is something that's a growing debate in the field. Now historically, it's always been viewed as the neoadjuvant chemotherapy followed by cystectomy is the ideal treatment for these patients. First line therapy and the trimodality therapy-- I guess I should specifically mention-- so trimodality therapy is where patients have optimal debulking with the TURBT, followed by concurrent chemotherapy and radiation therapy, followed by surveillance. So they felt that that trimodality therapy is best reserved for those patients that are not cystectomy candidates for a variety of reasons, comorbidities or other such problems. There's some growing evidence to suggest that perhaps trimodality therapy may be an equally effective way at achieving oncologic outcomes, ie, cures, at the same time, though, preserving the patient's native bladder, and therefore improving their overall quality of life. So this debate was highly instructive and very interesting. I will say, Dr. Cookson was pointing to the National Cancer Database information comparing retrospective data, but comparing the overall survival with radical cystectomy versus trimodality therapy, suggesting that radical cystectomy is more effective in achieving oncologic outcomes with cure. But Dr. [INAUDIBLE] appropriately pointing out that these are retrospective analysis and there's a lot of patient bias that goes into this, because again, historically, trimodality therapy is reserved for those patients that are not deemed surgical candidates, oftentimes because of comorbidities. So their worst prognosis patients, and you would predict that those patients have inherently a worse overall survival anyway. So it was a very instructive and intriguing debate, and I anticipate perhaps we eventually will see the gold standard of a randomized controlled trial performed, which will answer the debate. But very instructive, very interesting, and a great component of these meetings. Are there any other takeaways that were important during the symposium? As I mentioned, prostate cancer isn't the only disease area where there were some interesting and exciting clinical trials that came out that are practice-changing. We also saw a number in kidney cancer. The two highlights in this area were both asking the question, does a tyrosine kinase inhibitor, a molecule targeted therapy in combination with a checkpoint inhibitor improve cure rates over tyrosine kinase inhibitor alone? Currently, the standard of care for patients with metastatic kidney cancer is either monotherapy with the tyrosine kinase inhibitor or combination checkpoint inhibitor with ipilimumab and nivolumab. So we've seen some data come out recently looking at these molecularly targeted therapies plus checkpoint inhibitors. And so at GU ASCO 2019, we saw updated results on a number of things. One, on the updated results from ipilimumab and nivolumab, demonstrating that the complete response rate is somewhere around 10%, 11%. But then we also saw some updated results of axitinib plus nivolumab versus [INAUDIBLE]. In this trial, about 20% of patients had favorable risk disease, 65% or so had intermediate risk disease, and another 20ish percent or so had poor risk disease, so about what we typically see in clinic. And the response rates were high with the PD-L1-based therapy. The complete response rate was around 4%. The trials that we were really excited to see the results from was the KEYNOTE 426 study, which was axitinib plus pembrolizumab versus monotherapy with sunitinib. So again, this, similar to the others, w as a first line therapy. Patients were started on a lower dose of axitinib of 5 milligrams, and it could be dose escalated if it was tolerated. And the enrollment across the trial based on the risk categorization of INDC was similar to what we've seen in a lot of these trials. Again, about 30% of favorable, a little less than 60% had intermediate risk diseases, something around 15% had poor risk disease. So very similar to the other targeted therapy plus checkpoint inhibitor trials that had just recently been reported. The results were pretty encouraging. The hazard ratio was 0.69 for death or progression, favoring axitinib plus pembrolizumab. Around 90% of patients were alive at 12 months versus just under 80% for sunitinib. The complete response rate was around 6%. So again, very encouraging data. The one potential issue that we need to look to is safety as we're comparing these strategies versus the current gold standard immunotherapy approach, which is ipilimumab plus nivolumab. So the proportion of patients discontinuing treatment on this axitinib/pembrolizumab trial was 30% versus 14% for [INAUDIBLE]. And that's approximately what we see with the ipilimumab and nivolumab data. Again, this appeared to be well-tolerated and safe, and it seems to have advantages over ipilimumab and nivolumab in that regard in terms of safety. The big question that everyone's asking is, which strategy is more effective and [INAUDIBLE] a larger proportion of patients that have durable responses? These may be cures. Again, that number is around 11% based on the updated data that was presented at GU ASCO for ipilimumab and nivolumab versus in the 5% range that we're seeing so far with the axitinib-based combinations with either pembrolizumab or atezolizumab. So it's still fairly early with either of these trials. We need to see if with time the complete response rate improves. But overall, really exciting and really encouraging, because these combinations appear to be active, well-tolerated, and are definitely leading to durable responses in patients. That's great. It sounds very promising. Again, today, my guest has been Dr. Benjamin Maughan. Thank you for being on our podcast today. Thank you so much. I appreciate the time Lauren. And to our listeners, thank you for tuning in to the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcast.
Feb 20, 2019
Striking a Balance: Therapeutic Opioid Use In The Era of Overuse
Welcome to the ASCO Daily News podcast. I'm Alex Carolan, and joining me today is Dr. Sriram Yennu, an associate professor in the Department of Palliative Care, Rehabilitation, and Integrative Medicine at the University of Texas MD Anderson Cancer Center. Dr. Yennu works within the Division of Cancer Medicine. Today, Dr. Yennu will discuss opioid prescription use and cost among patients with advanced cancer in inpatient palliative care from an article he authored in the Journal of Oncology Practice. Dr. Yennu, welcome to the podcast. Thank you, Alex. The trend of opioid use in cancer is different than in other diseases because of unique pain brought on from the disease. Dr. Yennu, what do your findings on opioid prescription use tell us about that? Yeah, I think this is a very important topic for the cancer patients, especially in the metastatic setting. Cancer pain is one of the most debilitating symptoms, distressing for the patient. And a lot of times, the patient is very much unable to do things, what they like to do, socialize. And from the research, what we found from our previous studies was that about 60% to 90% of the patients have moderate to severe pain. And from the WHO recommendations and other recommendations, opioids are used for pain control as the first line of choice. And what we also found in the previous studies is that 75% of the patients, especially in the metastatic state setting, are on prescribed opioids. So this article really focuses on the patterns of opioid use. In the inpatient setting, whenever the patients with metastatic cancer are admitted in the hospital, they are being treated for pain, and we are looking at the opioids used. And more than 50% of the patients that are admitted in the hospital in the metastatic setting are seen by the palliative care unit. And so we looked into the patterns done by a single team that is a palliative care team in managing pain in this setting. What we found in this study is that whenever we prescribe opioids over a period of time -- we have been in the service at MD Anderson as a single team since 1999. We looked in for the patterns from 2007 to 2014. We found that the amount of opioids used has decreased. One thing for sure is that, though the amount of opioid use decreased, when they were admitted, the amount of opioids is increased, mainly because we wanted to manage their pain better. And a lot of times, the amount of opioids used at their home was not optimal. So that's the reason. The other important findings, what we found is the cost of the opioids from 2007 to 2014 has, in general, decreased. Actually, the pattern of the opioid cost decreased from 2007 to 2011, but because of the cost of fentanyl and other opioids after 2011, they were showing a striking trend in the opioid cost after 2011 to 2014. And these are some of the interesting findings for us because in the last, at least, three to four years, we have been having some trouble with access to opioids in the inpatient setting. There have been shortages, and the main reason is because of the recent drug overdose deaths. As you know, in non-cancer setting, the drug overdose deaths has been an epidemic trend. So they have been administrating opioids to the cancer patients, and this is resulting in significant pain issues. And this pattern that we are describing in this paper will be helping the policy makers. Cancer patients still need opioids, you should still provide some access to opioids rather than restricting it. And also, understand that the opioid addiction is a problem, but in cancer patients, pain control is a huge burden. That's very interesting. And your study's results found that for patients between the years 2008 and 2014, age, prescription year, and pre-admission opioid doses were significantly associated with opioid doses prescribed to patients with advanced cancer who received inpatient palliative care. How can health care professionals apply these results to real life practice? Yeah. I think let's go one point at a time. Younger age was associated with higher opioid use, and this can be taken into consideration that patients who are younger have a higher symptom expression, they can tolerate opioids better compared to older age. The main reason that older age patients cannot tolerate is because of the volume of distribution of the older patients are far less. So in general, the prescribers, that is, the palliative care clinicians, usually prescribe less opioids to older patients and that could be one of the major reasons. And the other thing could be that the amount of expression, as well as the association of pain in older patients was low. But I think we need to do further studies on why age is an important factor in the opioid prescription. The other is the earlier prescribing years. Because of more advances in cancer pain management, the more lately we have been using less opioids. That could be one of the important thing. One of the things that we are doing more is screening for patients with substance abuse. We are also setting up something very important, that is personalizing pain goals. So each patient should be customized or personalized to a given pain situation so that they can function optimally and have lower distress. And also the use of adjuvant medications has been also advanced since the earlier time we started prescribing. For instance, 2007 compared to 2014, the adjuvants are better. In addition to that, the non-pharmacological interventions has also increased. With the epidemic, there is more impetus to use non-pharmacological interventions, like using of acupuncture, hypnotherapy, physical therapy, and other aspects which are supposed to be helping now. There is more evidence, so we are using more of that. So that's actually helping using better armamentarium to treat the pain compared to just opioids alone. So that's the reason earlier prescription years was associated with higher opioid use. And the other thing is that patients who are higher pre-admission opioid doses have higher doses of prescribed opioids. This is really intuitive. A lot of times, if you have more pain, you have small, less symptom burden, you are already using a lot of opioids. So you will have a tendency to use more opioids during the inpatient admission. So that's one of the reasons why we feel that the patients who are using old opioids before they're getting admitted have higher tendency to use more opioids. So these are very important findings, and whenever a prescribing clinician takes care of the patient in the inpatient setting, especially in the metastatic cancer setting, if you use these factors into perspective, then you can able to optimize being better. For instance, if you are a senior patient using very high doses of opioids when they're older, than you need to be very careful. Is there a way that we can cut down the opioids? Is there a way that we are not diagnosing something which is important, like a fracture or something like that, so that we can stabilize it? And they are using high opioids now. There could be other reasons, like, is the patient having opiate addiction or something like that? Or is the patient been more anxious? Or is the patient expressing wrong because the patient has delirium? Those are the factors that I would be looking to if I am a prescribing clinician in the inpatient setting in a metastatic cancer patient when I look into the results of this study. And with findings that the opioid cost per patient decreased from 2008 through 2011 and increased in 2012 through 2014, how can we apply this information to our 2019 opioid cost trends? This is a very important finding. One caveat is that we didn't include the administration cost. We just used the cost of the opioids. The cost of the opioids definitely decreased from 2007 to 2011, mainly because the amount of opioids decreased significantly. And a lot of this is to do with the better screening and better assessment, and also in terms of the prescribing patterns. But the costs from 2011 to 2014 increased, and this is mainly because of the increased use of fentanyl and hydromorphone and these medications were more expensive after 2011. And that's something you want to be very aware of. And if you are a policy maker and you are worried about costs of medications, this is where you want to put some emphasis on when you are trying to be discussing in Congress or any other place, is the cost of medications are increasing and it is a increased burden for the patients. With opioids complicated use within the treatment of different diseases, how can this study mitigate what it describes as undertreated, intractable pain because of opioid underuse? The opioid use was the first line of choice for the cancer pain, and especially in the metastatic setting. With the advances we have in terms of assessment, screening the patients better, screening patients with opioid addiction, and also personalizing pain goals, use of adjuvant medication, use of non-pharmacological pain procedures, like using acupuncture, using hypnosedation, using various other strategies which have been now having more evidence. For instance, there is more evidence now to use acupuncture, there's more evidence to use hyponotherapy. So using all of these will mitigate the amount of opioid use, it could also mitigate the amount of opioid induced neurotoxic side effects, and help the patient to have a better quality of life. Because the patient before had no other choice but to take opioids for cancer pain. Now with the advent of all these different strategies and advances, we can use opioids but to a lesser extent and only if necessary. Again, my guest today has been Dr. Sriram Yennu. Thank you for joining us. Thank you, Alex. And to our listeners, thank you for tuning into the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate and review us on Apple Podcasts.
Feb 14, 2019
Key Takeaways from the 2019 Gastrointestinal Cancers Symposium with Dr. Stephen Leong
 Key Takeaways from the 2019 Gastrointestinal Cancers Symposium with Dr. Stephen Leong   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Welcome to the ASCO Daily News podcast. I'm Lauren Davis, and joining me today is Dr. Stephen Long, associate editor of ASCO Daily News. Dr. Long is associate professor in the division of medical oncology and is a translational researcher in the GI and developmental therapeutics programs at the University of Colorado Cancer Center. Dr. Long, welcome to the podcast. Thanks for having me. It's a pleasure to be here. Dr. Long, you've just returned from the Gastrointestinal Cancers Symposium. How was this year's event compared with previous years? First of all, I love you GI ASCO. I always find it informative. And I love the format of the talks and presentation. This year there was no significant practice changing presentations like in years past. However, there were still some excellent presentations and talks. And what were some of the presentations that stood out to you? There were some reports of a couple of clinical trials that sort of intrigued me. One was KEYNOTE-181. This was a phase III study comparing pembrolizumab monotherapy versus standard chemotherapy in patients with local events and metastatic esophageal cancer in the second line setting. They reported a significant improvement in overall survival in patients with PD-L1 combined positive score of greater than 10. And these patients received 9.3 months overall survival compared to 6.7 months for those who received [INAUDIBLE] choice of chemotherapy, which then consists of paclitaxel, docetaxel, or irinotecan. In addition, pembrolizumab was better tolerated and had a better safety profile. What made it really intriguing was of the total 628 patients that were enrolled in the trial, 64% of them had squamous cell carcinoma of the esophagus, which is unusual, especially in a phase II setting. And even though the study had a statistic overall survival benefit, in the squamous cell carcinoma cohort, there was a non-statistical trend in overall survival of 8.2 months versus 7.1 respectively. Pembrolizumab did boost the objective response rate compared with chemotherapy in the PD-L1 CPS greater than 10 and a response rate of 21.5% versus 6.1%. And then squamous cell carcinoma, it was 16.7% versus 7.4%. That leads to a whole bunch of questions. One, should we improve our PD-L1 scoring by including a CPX score greater than 10 and making our predictions based off that? In addition, should pembrolizumab expand its indications to include squamous cell carcinoma, since presently in the United States, pembrolizumab is only approved for adenocarcinoma. Also, there were the reports of the phase II ROAR study, which was looking at biliary tract cancers with BRAF V600E activating mutations. And these patients received a combination of dabrafenib, a BRAF inhibitor, and trametinib, a MEK inhibitor. There were 33 patients. And they had an objective response rate of 42%. All of them with partial responses. And 7 of the 14 patients with responses had the responses lasting more than six months. And adding those with stable disease, they had reported a disease control rate of 88%. They looked at survival data. And the median progression free survival in this cohort was 9.2 months with an overall survival of 11.7 months. And to put this into context, usually second line biliary tract cancers we rarely ever see survival being more than five months. And these PFS and overall survival is very comparable to the first line setting for gemcitabine cisplatin, where the original study showed a PFS of eight months and overall survival of 11.7 months. So this potentially could be another treatment option for people with V600E biliary tract cancers. And then there were the preliminary results of a single phase II study at Memorial Sloan Kettering, which was evaluating pembrolizumab in conjunction with trastuzumab HER2 antibody with CAPOX and those with HER2 positive metastatic esophageal gastric adenocarcinoma. They had 32 patients with the overall response rate of 87%. They reported three CRs and 25 partial responses. And then when you factor in the stable disease, they had 100% disease control rate. And all the patients had some degree of tumor regression. The PFS were 11.4 months with an overall survival having not been met after six months. This is extremely exciting, and this has already led to the development of a global phase III study, which will be known as KEYNOTE-811. That's great. That sounds very promising. Were there any research presentations that you were interested in? Oh, yeah. There was a lot of great preclinical work. One of the most intriguing was in pancreatic cancer, where the Canadians did a study known as COMPASS, where they took advanced pancreatic ductal adenocarcinoma, and these patients underwent whole genome sequencing, as well as RNA sequencing of their tumors, prior to the initiation of first line chemotherapy with either modified FOLFIRINOX or gemcitabine and abraxane. Treatment outcomes were then compared to their molecular characteristics. The data suggests that chemotherapy differs depending on the transcription features of the tumor. So for example, the best survival data came out of those patients with the classical ductal adenocarcinoma subtype that were treated with FOLFIRINOX. And they had a median survival of 7.17 months. And when they were compared to the basal-like subtypes and were treated with FOLFIRINOX, they had a median progression free survival of 2.5 months. Now, patients with the basal-like subtype actually had a better response to gemcitabine and abraxane, which had a PFS of 5.65 months compared to the classical subtype, where they had median progression free survival of 4.93 months. So in summary, those with the basal-like subtype actually had a resistance for FOLFIRINOX. In addition, the researchers also mentioned that GATA6 RNA expression significantly correlates to the PDAC classic and basal-like molecular subtype. So it could actually be used as a marker in determining subtypes. And all this put together means that we could potentially identify patients who have a better chance of responding to FOLFIRINOX versus gem abraxane in the first line setting in pancreatic cancer. And obviously there needs to be more work to validate this, but this actually is quite intriguing. Also, there was data from the amino scoring testing, which was looking at its test in high risk stage 2 colorectal cancer patients. And for those who are not familiar, patients with stage colon cancer have a poor prognostic if they had a T4 disease, had fewer than 12 lymph nodes removed, had a point differentiation subtype, and also had evidence of vascular emboli, lymphovascular invasion, perineural invasion, or actually had a presentation of bowel obstruction or bowel perforation. And these patients are often offered adjuvant chemotherapy following curative resection due to their high risk of recurrence. The amino score test measures the density of CT3 positive T cells, as well as cytotoxic CDH cells within and surrounding the tumor to gauge the strength of the host immune response at a tumor site. So therefore a high amino score indicates a high anti-tumor immunity, which correlates with a low risk for disease recurrence. And these investigators looked at 1,130 patients with stage two colon cancers. And their conclusion for time to recurrence was those with high risk disease with high amino scoring compared to those with low risk disease had a very similar five-year survival of 87.4% versus 89.1% respectively. In contrast, if you have a high risk disease and a low amino scoring, your five-year time to recurrence was only 72.2% in the absence of adjuvant therapy. So this could potentially be used as a prognostic tool for those who are high risk stage two in the future. What about education sessions? Were there any that caught your attention? So my favorite was the neuroendocrine session. Neuroendocrine, as most people know, is a pretty rare disease population. However, there has been significant advances in the past few years with new drugs, new understanding of the biology, new diagnostic procedures, as well as testing. And it was a great panel of leading experts to help us navigate the new landscape of neuroendocrine and understanding how we should be approaching this. So that was my favorite session. Were there any other takeaways that were important during the symposium? There were a few other presentations I thought that were quite interesting. The Japanese presented their Prep-02 or JSAP-05 trial. And this was the first study to ever demonstrate the efficacy of neoadjuvant therapy in resectable pancreatic cancer. And their neoadjuvant chemotherapy regimen was a combination of gemcitabine with an oral drug S1. And they showed that it met its primary endpoint of overall survival of 36.72 months in those patients who received neoadjuvant therapy versus 26.65 months in those who went from upfront surgery. And for the Japanese, which tend to do upfront surgery followed by adjuvant chemotherapy in the past, I think this may be a shift in their paradigm, where this could be the new standard in Japan of using neoadjuvant therapy prior to surgery. Also, there was the oral drug trifluridine and tipiracil, which was studied in a phase III metastatic gastric and GE junction adenocarcinoma for those who have received two previous line of therapies. And they were randomized to the drug versus placebo. And it demonstrated a 2.1 survival benefit over placebo. And their main concern was a lot of these patients end up getting gastrectomies. But being an oral drug, could that affect its efficacy? And it seems like this benefit was also seen in those who had a gastrectomy versus those who didn't as well. So this potentially could be another option for those in the third line setting for gastric cancer. However, the big debate is even though it met its overall survival, is 2.1 months clinically significant? And I guess we'll have to have more data regarding safety and tolerability before we can make that decision. There is also the French GRECCAR-6 trial, which was evaluating the optimal time to surgery following chemoradiation for rectal cancer, where patients who underwent neoadjuvant chemoradiation were randomized to waiting 7 or 11 weeks prior to a mesoresection of the rectal cancer. They demonstrated that they had very similar path CR rates between the two. But more interesting, they found that if you had a good disease response to chemoradiation, there was no difference in disease free survival if you waited 7 weeks versus 11 weeks prior to surgery. However, if you were a bad disease responder, you had a poorer disease free survival if you waited more than seven weeks. However, this was not statistically significant. And then the authors concluded that we shouldn't be waiting more than seven weeks prior to surgery following neoadjuvant chemoradiation for rectal surgery. Thank you so much. Again, today my guest has been Dr. Stephen Long. Thank you for being on our podcast today. And to our listeners, thank you for tuning into the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple podcast.  
Jan 24, 2019
ASCO Podcast Coming Soon: Exclusive Interview with FDA Commissioner Scott Gottlieb
Jan 23, 2019
An Introduction to Interventional Radiology with Dr. Alexander Kim
Welcome to the ASCO Daily News podcast. I'm Lauren Davis. And joining me today is Dr. Alexander Kim, chief and residency program director of vascular and interventional radiology at Georgetown University Medical Center. He specializes in interventional oncology, and his practice is focused on locoregional cancer therapies. Dr. Kim, welcome to the podcast. Thanks for the invitation, Lauren. I'm happy to be here. Today we're talking about a somewhat new subspecialty in oncology-- interventional radiology. This can be used as both a diagnostic tool and a tool to administer therapies. How does that work? So interventional radiology is a field where we use image guidance to perform minimally invasive procedures. So all of our procedures are performed under ultrasound, or CT, or sometimes MRI. And we're able to advance needles and catheters into places that, 15, 20 years ago, we weren't able to reach. And in terms of diagnosis, this has really revolutionized cancer management. So for a patient with a nodule in in their abdomen, let's say, who previously may have had to go to the operating room for a biopsy and diagnosis, that patient now undergoes a same-day procedure in IR and just gets the CT biopsy performed. From that, it led to more and more therapies being developed, where we're now able to go in and treat various cancers in the kidney, and the liver, and lungs using the same techniques. So how new is this technology? And how has it changed the way medicine has been practiced compared with, say, 10 years ago? Interventional radiology is a subspecialty of radiology. And it actually initially was called special procedures. And that's been around since the '50s and '60s. Really, the dramatic change has really taken over in the last 10 to 15 years in terms of cancer care. And I like to think that we're one of the forefront specialties in the move towards minimally invasive procedures. So again, whereas 10 years ago a patient may have had to go to the operating room for various procedures which required a patient to stay in the hospital for an extended period of time to recover after their surgery, with treatment and diagnostic modalities that we have, this really limits their hospital stay. And I think that's probably the biggest contribution that interventional radiology has made into the field of medicine-- is really minimizing the length of stay and, in turn, the quality of life of patients who may not have that much to live with their disease. Tell me, what kind of program have you developed that your cancer center? So we have a large interventional college of practice at Georgetown. We have a large NCI-designated cancer center, the Lombardi Cancer Center, where we get a lot of patient referrals from. We are also a large transplant center. And through that, we see a lot of HCC primary liver cancer patients. And one of the things that really benefits us is, really, the collaborative group that we have who work with us. So our medical oncologist, and our surgical oncologist, and the radiation oncologist colleagues are really very pro-minimally invasive treatment. They're very local therapy friendly. So oftentimes, they're very open to different therapeutic suggestions that we bring up at our various multidisciplinary conferences. And I think that's really helped to grow our practice and helped it thrive. What are some of the challenges in creating such a program? You know, I think buy-in. Interventional radiology is a very under-recognized specialty, even within medicine. Part of our issue-- we have an identity issue. People outside of interventional radiology aren't really familiar with the things that we're capable of doing. So I think it requires a lot of effort amongst interventional radiologists who go to the multidisciplinary boards, and speak up, and say, hey, we could maybe approach this patient in this minimally invasive way. And after a while, that trust is built. So a lot of the groundwork-- having open-minded colleagues certainly helps. Absolutely. And what are some of your measures of success? In terms of the collaborative effort that we have, in terms of our overall patient management, the collaboration that we have, the open-mindedness to our input, I think, kind of defines our success within the hospital. And obviously, in terms of patient care, we want to make sure that we're at the forefront of research and producing good outcomes for the patients that we take care of. And will these procedures that you do through interventional radiology-- do they increase progression-free survival or lead to possible cure rates? Yeah, and I think a good number of our procedures do improve survival. A lot of the patient population that we see in integrative therapy is palliative. But there are more and more data that's coming out showing the potential survival improvement with our treatment. So recently, a study was published out of Europe. It's called the CLOCC trial, where they compared systemic chemotherapy alone versus chemotherapy plus ablation for patients with colorectal cancer with liver-only metastases. There was a significant survival advantage in patients who underwent ablation plus systemic chemotherapy. And in fact, 35%-- actually, 36% of those patients were alive at 9 years, which is a pretty incredible finding. And there are other studies in other disease processes that are coming out that show that these minimally invasive therapies can potentially have curative effects. We need more data like that. But the data that's coming out, I think, are very promising. That's wonderful. Again, today, my guest has been Dr. Alexander Kim. Thank you for being on our podcast today. Thank you very much. That was really fun. And to our listeners, thank you for tuning into the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcast.
Jan 17, 2019
Developing a Resectable Pancreatic Cancer Program in India with Dr. Shailesh Shrikhande
Welcome to the ASCO Daily News Podcast. I'm Lauren Davis, and joining me today is Dr. Shailesh Shrikhande, who is the professor and head of cancer surgery and the chief of GI and HPB surgery. He also serves as the director of Tata Memorial Hospital in Mumbai, India. Dr. Shrikhande, welcome to the podcast. Thank you so much. It's been a real pleasure to be here on this podcast. Today we're talking about pancreatic cancer in India and the challenges of creating a surgical program to treat this cancer. Of the 18 million cancer diagnoses predicted worldwide in 2018, nearly half a million will be in pancreatic cancer. In India, the rates of pancreatic cancer are also on the rise. What do you attribute this increase to? So I would like to answer this question in two parts. One is that pancreas cancer still remains an uncommon cancer in the Indian subcontinent as compared to the Western world or the Caucasian world and even the Far East. We do not really know the reasons as to why the incidence is quite low in the sense that in the United States the incidence is about 15 per 100,000, but in my country it's about 4.1 per 100,000. So it's about one third the incidence one sees in the United States. Having said that, India is the second largest most populous country in the world. And we have clearly a large population with increasing awareness. So we have the urban population, and there is a 5% to 10% shift from the rural parts to the urban parts of India, and that's where we start to see this cancer more and more than ever before. So a decade ago, we definitely saw much less number of cancers which were pancreas and [INAUDIBLE] cancers. Now we see them in large numbers. The reasons are twofold. I think one is increasing awareness and widespread availability of diagnostics. Actually, even in not just in the metropolitan cities, but in tier 1, tier 2, tier 3 cities, and even in the smaller towns, you have much better imaging across India. As you know, India is a country which resides in different centuries at the same time. So this is not universally distributed across this country. But clearly, we are able to detect them more. So I think part of it is increased incidence, part of it is increased awareness and detection, and this is resulting in we perceiving an increased threat of pancreas cancer in our country. The real reasons for this rise is I think modern world, urbanization, environmental factors, smoking and alcohol, which continues to be on the rise in a country like this. India is also the diabetes capital of the world. And we do not know which of these factors or an interplay of these factors are contributing to the gradual but definite increase in [INAUDIBLE] and pancreatic cancers in India. What is the current surgical strategy for treating pancreatic cancer? And what new treatments do you envision for the future? The current surgical strategy is something which actually hasn't changed, but has just got refined over the last three decades. This has happened worldwide. And India is also no exception, especially in centers like ours. So complete radical removal of the cancer, the best of surgical techniques, is perhaps the only way to give the patient a chance of a complete cure. So the current surgical strategy is if the disease is localized, if the disease has not spread, is not metastatic, if the patient can withstand a supra major extensive resection, the best thing is to do a radical surgical operation and remove it. Some of these tumors in selected patients can be removed laparoscopically or by robotic means, while some of them will continue to receive conventional surgical approaches. As regards new treatments, what has really changed over the last decade is the fact that it's no more just a domain of the surgeon to cure pancreas cancer. You need the medical oncologists. You need the radiation oncologists. You need the genetic specialists. You need the people who understand the molecular biology of the disease much better as we move in the era of precision medicine. And therefore, you are able to individualize the pancreatic cancer and perhaps offer them a whole battery of treatment, and it's not just surgery. Having said that, surgery remains at the core. But as you would know that if I were to see 100 patients of pancreas cancer in my clinic, I'm able to offer surgery to about 30 or 40 of them, because 60 of them would present to us already at a stage where it has metastasized. It's not just localized to the pancreas, but it's spread elsewhere. So we need to look at not just the curable, resectable disease, but we also need to look at what are the other avenues of evolving chemotherapy, and so on and so forth. What kind of program have you developed at your cancer center? So what we have done is, it's been an ongoing journey. And it continues to be an ongoing journey even now. And in this particular situation, renal center where in the late '90s, in the early '90s to be precise, we already went into an organ-based vertical split in the department of surgery and medical oncology and radiation oncology. So way back in 1992, something which is revolutionary for a country like India, we had people who were specializing in gastrointestinal cancer surgery, and then we had people specializing in thoracic surgery, breast surgery, uro oncology, so on and so forth. We still have a large number of surgeons in India who would be practicing surgical oncology, but this center made the change in 1992 to move on towards specialized mission. And now we are no more gastrointestinal surgeons. We are pancreas surgeons, liver surgeons, gastric cancer surgeons. So we've got further super specialized as far as development of surgery's concerned in this center. But in the last decade, we've also moved on to the concept of a disease management group. So we have the gastrointestinal disease management group, wherein it's not just the surgeons, but the medical oncologists, radiation oncologists, pathologists, interventional radiologists, molecular biologists, nuclear medicine specialists, all of them are specialized and focused only on to gastrointestinal cancers, thoracic cancers, uro-oncology cancers, thymic cancers, so on and so forth. So one of the programs that we have developed is to focus and develop complex organ surgery, like pancreas surgery, G2 extended gastrectomies as well as liver surgery, to speak for my speciality. And this has happened over a period of time. So just to give you an idea, when I started way back in 2002, at that point in time, we were doing about 25 Whipple resections a year, which is removal of the pancreas head. This would mean that we were doing about two of these operations or three of these operations in a month, and we would average somewhere between 30 to 35, at best, pancreas resections in 2002 when I was just joining [INAUDIBLE] the staff. 18 years down the line, we are already doing about 200 of these resections a year. So we are clearly a high volume center. But this has not happened overnight. It happens because of a sustained focus in developing that. Then the administration is also looking at the kind of perioperative outcomes and the transfer and documentation that we have. We have prospective databases, which establish the fact that we are a center of excellence. But it's not just the surgeon. It's also the paramedical staff, the intensive care, the intraoperative assistance from the OR nurses and other people, as well as the pain clinic, the anesthesia is now specialized. All this has developed over a period of time. The residency program has also evolved. So in 2010, we became the center for training surgical oncologists for the whole country. We've been traditionally doing this, but now we have a specialized residency program. So nearly 55% of the cancer surgeons and the oncology skilled workforce in this country undergoes training at the Tata Memorial Center, which is India's largest cancer center. Just to give you an idea, we have seen 73,000 new patients of cancer last year in oncology. So this kind of workload has resulted in the gastrointestinal and HPB surgical service to not just double, but triple the number of registrations and the number of patients coming in to seek treatment from us. And this is the kind of program that is ongoing, and it has developed to a stage where we are able to document this work and attract more work [INAUDIBLE]. That's great. And what have been some of the challenges in creating such a program? So I'll tell you one thing, as I did mention earlier, that India lives in different centuries at the same time. So we have islands of excellence, no doubt, but it's not that training and education is standardized across this country. So you will have institutions and you will have programs which are very well designed for young doctors, and they will develop well over a period of time. But as you would know, multidisciplinary care does not mean only clinicians. It does not mean only a surgeon. It does not mean a medical oncologist and a radiation oncologist, and they complete the entire comprehensive oncology management of a patient, not at all. So we need to improve in areas where it comes to nursing, where it comes to intraoperative nursing, where it comes to diagnostics. So all of these things, which I, today, in 2018, take it for granted, was not something which was very well established when I joined on the staff in November 2002 as an assistant professor. At that point in time, one had to align the other people around into believing that excellence is something which happens with a lot of people working together, so that you can achieve an uncommon goal. First of all, it's difficult for them to see what goal we are talking about or what destination I am trying to take them to. And the second is to keep them motivated and make them enjoy the process. It can be just a dreadful job, but something which you can pursue with a lot of passion, and infuse that kind of enthusiasm and passion and motivation, so that the others also kind of come together. And then teams are the things that matters the most, if you ask me. So these were the challenges when it came to convincing people. And at that time, initially, you don't have too many people who go with you. But once you start doing all the work yourself-- and you may be leading the particular program, but actually one needs to work the hardest yourself. And then when you start seeing the results coming, and the others are also getting motivated and joining you. So these were clearly huge challenges in the beginning for the first three to four to five years. But each year, we started documenting our work, we started publishing our work. And once you start doing that, people notice it. So good work or good news takes time to spread. Bad news spreads very fast. But good news takes a little while. But this has taken a while. And then our statistics and data clearly show the kind of increasing work and recognition that we have got in the past decade. Do I have challenges now? We clearly have challenges, because we have the advent of laparoscopic and robotic surgery. We have the robot with us. But the next round of challenge is, this is a complex surgery, where people need to be trained first in conventional surgery. If they do this complex surgery well in the conventional fashion, then they need to make the transition to laparoscopic or minimal access or robotic training. Then we also need to factor in increasing costs, which are very relevant to a country like India. Not just in India, even in the United States this is important. And these are other challenges for me to make this program not only sustainable, but also grow. The next challenge I have is I have so many patients. We are a country of 1.2 billion. And the number of reference are such that perhaps this center has the potential to do about 300 to 350 resections, but we are today able to do only 200 simply because I have a logistics problem. I have a manpower problem. I have a limitation for the number of ORs that I can utilize in a week. When I started out, I had six ORs a week. Today my overall gastrointestinal team has 15 ORs a week. And we have six ORs only for pancreas and gastric surgery. And even then, I have an embarrassing wait list of about eight weeks. This eight weeks may not be a lot if you compare with some health systems like the UK and Canada. But when a patient gets a cancer and [INAUDIBLE] to an aggressive cancer like a pancreas cancer, people, if they are fit enough to undergo surgery, would want the surgery to be done not tomorrow, but yesterday. So these are challenges for us in trying to expand this program and make it better. But certainly our experience in the last decade encourages me to be confident that we will be able to expand it more and more in the next few years. So I'm curious, what are your measures of success in treating patients with resectable pancreatic cancer? So it's very clear. These are the standard internationally accepted to specific areas. And the measures would be the perioperative outcomes for resectable disease. How good is the quality and completeness of surgery, which is dependent on surgical training, surgical experience, surgical volume, as well as hospital volume. And beyond that, it's also about the quantity of pathology that you have with you, and the quality of medical oncology, and the kind of chemotherapy and radiation therapy that we offer. So immediate outcome is the perioperative outcomes. And when I say perioperative, it's not just the 30-day mortality. It's the 90-day mortality that one should look at. And one should look at the standard outcome measures for morbidity based on something like the [INAUDIBLE] classification for grades of complication. So if you're able to objectively look at every month's audit, how well you are doing for complex surgery when we treat them with surgery for resectable disease. But the real measure of success as an oncologist and as a doctor who's aiming for a cure in a very aggressive cancer is also the long-term outcomes. But unless you have good short-term outcomes, you can't even hope to have a good long-term outcomes. So have we done very well in terms of short-term outcomes? Yes. Our results are comparable with the very best in the world. Any center worth their mention, we would be able to feel satisfied that we do as well as it's done, say, in America, Japan, Germany, wherever you have these centers of excellence. Now, the long-term outcomes is also much dependent on human biology. But if the patients do not have morbidity and very low mortality rates, these are the very patients who are going to get post-operative chemotherapy as well. If you develop too many complications, then they take time to recuperate, and then the time to start in chemotherapy also gets delayed. So surgery remains the backbone. But in addition to that, chemotherapy has improved the outcomes of pancreas cancer. So we want the patient to go on to chemotherapy soon after. And then the measure, of course, is after good complete radical surgery and complete high-quality chemotherapy, how long are the patients living? So I would divide the long-term measure into periampullary tumors, which we tend to see in large numbers in my country, and the classical pancreas cancer or the pancreas ductal adenocarcinoma. Our five-year survival rates would be about 20% to 25% for pancreas ductal adenocarcinoma after complete resection. This happens because the vast majority of tumors that we would resect would have disease which is not just localized to the pancreas, but it's already spread to the lymph nodes by the time we operate on them. The small percentage of patients in whom the disease does not go to the lymph nodes, you will have about 40% to 60% of them who are alive at five years, if not longer. The periampullary tumors are actually the better tumors who offer the more complex operation. But there we can hope for success rates of 40% to 60% at the end of five years, even with lymph node-positive disease. So these would be my measures of long-term success in addition to measures of short-term success, which is based on perioperative outcomes. And it sounds like you touched on my next question a little bit, where I'm wondering if these procedures increase progression-free survival or lead to cure rates. Yes. So I think I partly did address your question. The fact is that if you leave disease behind and you do incomplete surgery, you are definitely compromising your so-called PFS or progression-free survival. Progression-free survival should be a good terminology to use provided you have completely removed the tumor in the first place. I know that pancreas cancer is considered to be a systemic disease, and it indeed is one. I also know that you can have circulating tumor cells in the blood, which as yet are not easily detectable with any of the modern diagnostics. So I know that a number of patients which we operate, thinking that they are resectable disease, may, in fact, be having sleeper cells elsewhere which get activated soon after surgery or any form of treatment. And these patients might fail early. But it's not the fault of surgery that they fail early. It's just that the disease is more aggressive in these patients. But in those patients in whom the disease is truly localized, a well-done operation will certainly ensure that you get a long progression-free survival. And as I maintained before, you can try and give only chemotherapy or radiotherapy or targeted therapy or immunotherapy and not offer surgery, you will not get patients who are getting cured. You might get a degree of control. You might get a degree of downsizing. Patients will feel well for a period of time. But the chance of a cure is lost. So I say this not because I am a surgeon, but because that's where the objective evidence-based data is available for a large number of years. This is not data based on the last one decade. It's about three to four decades that we have good data that if you can completely do these radical procedures in well-selected patients-- and to remind you, these are only three or four patients out of 10. We are operating only on three or four, not all of them. But in these patients, if you do a good operation, you will certainly give them a chance of cure or a longer progression- or disease-free survival. Very informative. Again, today my guest has been Dr. Shailesh Shrikhande. Thank you so much for being on our podcast today. Thank you so much. And to our listeners, thank you for tuning in to the ASCO Daily News Podcast.
Dec 20, 2018
Key Takeaways from the Palliative and Supportive Care in Oncology Symposium with Dr. Kavitha Ramchandran
Dr. Kavitha Jennifer Ramchandran, Clinical Associate Professor, Medicine - Oncology at Stanford University. Her clinical focus is in Thoracic oncology and palliative medicine. Dr. Ramchandran served on the Planning Committee for ASCO’s Palliative Care in Oncology Symposium and is here to talk about the event.   Welcome to the ASCO Daily News podcast. I'm Lauren Davis. And joining me today is Dr. Kavitha Ramchandran, clinical associate professor of medicine of oncology at Stanford University. Her clinical focus is in thoracic oncology and palliative medicine. She served on the planning committee for ASCO's Palliative Care in the Oncology Symposium and is here to talk about it. Welcome to the podcast. Thank you. Today, we're talking about the Palliative Care in Oncology Symposium. Palliative care, which is really lessening the burden of disease and side effects of treatment, is having a moment. It's becoming more prevalent during earlier phases of treatment, not just at the end of life. How do you think we got here? Palliative care is a field in evolution. We've had opportunities over the last 40 years to see palliative care really evolve both in Europe and in the United States. As many of you know, palliative care actually stems from the hospice movement and was started with the hope that we could provide quality care for patients who are at the end of life. The goal was really to enhance a multidisciplinary level of care for all patients and with a focus not only on their physical needs but also on their psychological needs, spiritual needs, and social needs. What we've realized over time, especially in the last 30 to 40 years of medicine, is that we've made a huge leaps in terms of disease modification. We have new indications for new treatments every single day, with up to three to four new drugs being approved for cancer therapeutics every week. And that excitement has spawned this amazing rush for us to be able to try to cure and to lessen the impact of illness. However, we're also realizing that in doing that, we've also created an amazing epidemic of long-term toxicity and long-term needs that have to do with patients who are living with illness longer. And what this means is that palliative care has changed its scope, where we now are not only caring for patients as they come to the end of life, but we have to think about what it means to care for the whole person from the point of diagnosis, including caring for their symptoms, caring for financial toxicity, looking at the adverse events of some of these new treatments, paying attention to the caregiver and family as they negotiate complicated disease management. It's really about going back to whole person care but starting at the beginning because people are living longer, and disease management has become a lot more complicated. Absolutely. So I'm curious, what information from the Symposium do you think will yield the most changes going into 2019? Thanks for asking. I think this was an excellent meeting. I really hope some of you could have been there in person and are enjoying the newsfeeds post-meeting. I think one of the things that came out of this was some of the research on communication. We are in an era with new treatments that promise amazing things, including the possibility of cure even for disease that we once thought was incurable. And with that comes the need to really balance new communication strategies. There was a group of researchers that presented data on concepts of hope and optimism and how we balance that with realistic expectations and uncertainty. What we found was that hope unopposed actually can lead to patients receiving more toxic treatments and that those patients who had physicians who were able to talk a little bit more about uncertainty and provide a balanced approach often received treatment that was more appropriate for them in terms of their illness and their illness trajectory. Additionally, if you always offered hope, patients often had lower understanding of their prognosis and had a lower rate of advance care planning. I think this really allows us to think about how we educate our clinicians about balancing hope and uncertainty. Another piece that came out was in this era, we're really struggling with the use of opioids. We've had a lot of dialogue around the opioid crisis in the United States with an increase in opioid overdoses. And we had a great panel discussion on the great opioid debate in this meeting, specifically on how we treat patients who have malignant pain and how we provide them the medicines that they need to control pain. What stood out for me, here, was that we really need to think about addiction and malignant pain as two separate issues. If you have a patient with a history of addiction, it's important to get help from an addiction specialist so that you can still provide the medicines and the care that you need but you also get the advice, as a practitioner, that you need in order to care for those patients. Finally, we learned a little bit about guidelines and whether those guidelines are being followed. Dr. Rolland presented some data on high emetogenic chemotherapy. He found that even though we've had guidelines for many years on taking care of patients who are receiving high emetogenic drugs such as carboplatin and cisplatin, as practitioners, we're not actually following guidelines. We're not providing those patients with the right medications to control nausea and vomiting. And our adherence is often under 30%, resulting in poor quality of life outcomes for those patients. And finally, we learned a lot about digital health. We learned about an AI harness platform from our Boston group that would allow for us to better understand patients' pain. We also learned about EMR interventions that would help us to shorten the time to get patients the right treatment for painful bone metastases and that we can learn a lot about what patients think by following their thoughts and voices on local message boards through some of the work that was done by [? Cindy ?] [? Baggerwall ?] at Santa Clara Valley. How should oncology practices use the information from the Symposium to move the field forward or make process improvements? In the area of communication, I think that we have a steep challenge. We really need to learn to figure out how to communicate both hope but balance that with uncertainty. And I think those skills can truly be trained. But that needs to become a focus of our oncology training programs for all practitioners, whether they're in nursing, social work, or physicianship, to really think about how we learn those skills early in our training and practice them. Our patients look to us for so much, including not only the latest cure and the newest science, but they're also looking to us as guides. They expect us to be able to provide them some honest guidance on what they should do next. And that needs to be couched with both data but also our true perspective on what we think might happen next. And we need to be able to communicate that with compassion. I think that can be an area that we should be looking at educational ways to measure our competency there and see whether that really helps patients make good decisions and help us guide them to make the decisions. With regards to guidelines, I think that we've learned that research helps us to provide new guidelines. For example, with the high emetogenic chemotherapy, we have learned which drugs work. We've created the guidelines. Now we need a systems approach. We need to think about how we can use the EMR to help us to integrate those guidelines into our e-health solutions so that we make it easier for our clinicians to do the right thing. Similarly, when we think about our new research in neuropathy or in menopause-related symptoms, both of which were also presented, once we have data and good research and good guidelines, let's create a systems-based approach that allows us to integrate it into our technology so that we can make it easier for our clinicians to practice what we know is correct. And then finally, I think that we need to keep listening to our patients. We have a whole new host of ways of learning about what people are thinking, whether it be social media or discussion boards. And we're going to keep learning from them. So let's not forget to use that data and make sure that it helps us to figure out how we should be talking to patients and where they're learning their information from. That will help us to make sure we're on-target with regards to the relevance of the message that we're communicating. Is there anything else specific about the Symposium that you would like to mention? Yes, I think that there's two really interesting areas that were highlighted at the Palliative Oncology Symposium that we're just starting to learn more about. I think we're in the area of early research and thinking through the appropriate interventions in order to move these two fields forward. The first is looking at the adverse events of immunotherapy. This is a field that we learned a little bit about from the early trials that looked at comparing immunotherapy to chemotherapy. And most of those trials indicated that immunotherapy was relatively safe and that most patients tolerated it without too many side effects. But our palliative care colleagues were able to highlight the fact that actually, in the real world, we're seeing higher rates of toxicity compared to what was shown in the studies. I think that we're going to have to keep following this cohort of patients that are receiving immunotherapy over real-time. And we're going to have to decide, what are the true rates of these adverse events? There will also be a new field on really learning how to understand which patients are at highest risk. I think that, in a similar way that we understand perhaps which biomarkers predict for how patients respond to certain treatments, we'll also have to start to think about what biomarkers might predict which patients receive toxicity from these treatments so that maybe we can either counsel those patients better or plan for those toxicity. And I also think it's going to be important for us, as oncologists, to learn how to manage these toxicities long term, whether it be utilizing steroids or managing endocrine problems or hepatitides or pneumonitis. These are all areas that we're all learning a little bit more about as these drugs become more widely used. The second area that I think is really important but in a very different vein is financial toxicity. There was a active and new group of researchers that presented their work, including Yousuf Zafar and his team, as well as [? Ian ?] Oliver. And they asked us to ask patients and families a very simple question. Are you able to afford your care? As physicians, we often divorce ourselves from the financial impact of our treatments on patients and families. Unfortunately, it's no longer ethical for us to do so. These drugs are coming at great expense even though they also have great promise. And many times, patients and families are put in a very difficult situation between choosing something that could help them to extend their life versus not maybe having enough money in order to afford their basic living needs, such as housing or food. And, as physicians, we need to at least open that door to ask that question so that we can get them the right support that they need if finances are becoming difficult. I think that we're going to see a lot more work on this topic. And I think that we're going to be changing the way that we practice medicine so that we at least start to inquire and start to create systems that allow for patients to get the care that they need but also to be able to live their life in a way that allows them to get their other needs met, both for themselves and their caregivers. Again, today, my guest has been Doctor Kavitha Ramchandran. Thank you so much for being on our podcast today. And to our listeners, thank you for tuning into the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcast.
Dec 06, 2018
Communicating with Patients about Financial Toxicity: Dr. Ryan Nipp
Communicating with Patients about Financial Toxicity: Dr. Ryan Nipp Welcome to the ASCO Daily News podcast. I'm Alex Carolan, and joining me today is Dr. Ryan Nipp, a gastrointestinal oncologist and health services researcher at the Massachusetts General Hospital Cancer Center. Dr. Nipp, welcome to the podcast. Thank you. Thank you so much for the opportunity. Of course. Financial toxicity is a big factor in how patients with cancer approach treatment. Dr. Nipp, how do you talk to your patients about this issue? It's a great question. I think there are a number of ways to somewhat, you know, bring up this topic in clinic with patients. I don't know that there's one correct way. I think it somewhat depends on the person, depends on the patient and how well you know the patients, somewhat depends on when the topic may come up and how it comes up. So, often, when we meet patients for the first time, we have a multidisciplinary discussion about the treatment plan, the options, and potential side effects, and side effects related to the cancer and the cancer therapies. And that's where I've started taking the opportunity to say, how are things going? Any issues with nausea, pain, bowel issues? And at that point-- also, kind of bring up the thought of sometimes therapies can be expensive. Sometimes when people get sick, they have to take time away from work. Has any of this affected you up to this point-- and kind of just opening up the idea to are there any issues. At other times, they'll be issues that come up throughout treatment where someone's having trouble with insurance covers or co-pays or getting to clinic on time or finding a ride. And so that will be another opportunity where people kind of offer you this opportunity to bring up the idea and at least start to discuss it and see if it's a problem. And, you know, for the most part, people welcome the question. A lot of the time, people are like, no, I'm doing fine, but thank you for asking. But for those certain people where it is a problem, I find that it's a huge problem. And they're incredibly relieved to hear about it and have the opportunity to talk about it. That's good to know. And with that in mind, how do you create treatment plans while taking financial toxicity into consideration? Yeah. This is a little bit difficult. I don't know that there's any correct answer. I think that you have to be mindful. It's just like you would with any other toxicity that you're dealing with. If you know a therapy is going to cause nausea, you have nausea medicines. If you know a therapy may have cardiac side effects, you think about discussing that with the patient, letting them know the risks, you know, what are the percentages and the potential that this could happen to them. And just so that people know that down the road it's not a surprise if and when something happens, you almost have that obligation to bring it up. And that's the way I've started to categorize financial toxicity in my mind as well. It's another side effect that could come up at some point. If it hasn't come up yet, it may come up at some point. And you don't want to surprise patients with it. I think that's one of the big issues right now with financial burden that patients encounter throughout their care or that they're just worried about it. It's just this unknown of you hear about the financial toxicity of cancer. And it's so scary when you've got a new diagnosis. There's so many things that you're dealing with as far as symptoms, and job, and family, and how are you going to handle this, and just coping with so many other things. And this is another thing, just the uncertainty of what things may cost-- co-pays. Do they have insurance? Can you get time away from work to do this? And so I think it is just something to bring up that it could happen down the road, that this does happen to some people. And then that kind of brings you to the point of what options are available for people if and when that does happen. Similar to where if you had nausea or diarrhea that people may be experiencing, you can say, if and when that happens, we've got resources available. And here's what we have available at our institution. And, increasingly, there are more options available to help patients. And so I think that's something that clinicians, you know, throughout the clinic, you know different clinicians-- social work, financial navigation, MDs, nurse practitioners, physician assistants-- can help with, just kind of getting familiar with what the institution may have, may not have, what's out there in the country as far as other resources and things going on to help. Right. How does financial toxicity affect patient quality of life and treatment outcomes? Yeah. That's where I think a lot of the research has been growing in recent years is kind of describing that this is a huge problem for patients. I don't think it's all patients. But definitely, for those patients where a financial burden or financial toxicity is an issue, it is a major issue. It has shown in multiple studies now to negatively correlate with patients' quality of life. And then interestingly, if you think about, you know, the financial toxicity and financial burden that patients may be experiencing, it would make sense that that might impact how patients may adhere to certain medications. Might patients, if they're experiencing financial burdens, not want to pay for their Zofran or pay for other medications that might help them with side-effects of treatment. And then that point, you know, if you're not adhering to certain medications that you may or may not have needed, then that's a barrier to getting adequate symptom control, supportive care, and then ultimately could affect outcomes related to cancer therapy if you're also not able to adhere to your chemotherapy regimen or schedule and having to, you know, miss trips or missed visits-- another way that it can impact patient outcomes. And there have been studies showing associations with financial burden and adherence to medications and, if you take it even further, to potentially affecting patient survival. In what ways can oncologists ease patient burden through advocacy or financial navigation programs? I think advocacy is a good way to put it, meaning that you are kind of their advocate at this point, where, as a clinician, you may or may not. That's one of the barriers right now within the world of oncology, that we may not actually even know that our patients are struggling with financial burden or we may not know how much their copay is. We don't understand what their insurance may or may not cover or what certain drugs might cost. And so it's going to be somewhat of a learning curve with all of us as far as, you know, I've seen patients with this before. I have understood that this medication can be expensive. Or I understand that this medication is needing to be frequently refilled. And so this may, you know, add to the cost of your care. So you're their advocate. Knowing that you've had experience with this before, it might actually, you know, behoove them to be thinking about this could become expensive and just to let them know about that, that it could be coming down the road. And then that gets into, well, what are we going to do about it if and when the financial burden, you know, hits or becomes a problem. And that's where there's more and more research that's needed. I think there's a lot of research underway looking at financial navigation programs, financial counselors. Social work has been really helpful at our institution. I often go to other clinicians, the nurse practitioners or mid-level practitioners, that are helping us in clinic that have done this more than, you know, others and have seen this before. And are there programs available as far as getting reimbursements or some way to help patients with their co-pays? We've done a little bit of research here at Mass General as far as helping with patients to stay enrolled on cancer clinical trials to, you know, somewhat as far as the travel and lodging that's related to the frequent visits associated with clinical trials. Could you reimburse for some of the travel on lodging and help, you know, alleviate some of the financial burden? And that's one strategy. Again, how sustainable and how scalable that strategy is in question. But at least, you know, there's people out there thinking about it. I understand there's, you know, a good number of start-ups. There's multiple advocacy groups, online communities, that are thinking very hard about this. And how can we do more research and better understand the problem in order to intervene upon the problem? What role can research play to help patients and oncologists stand on the same page regarding the effects of financial toxicity on their treatment? Yes. I think this is a very important point. I think getting patients and clinicians on the same page regarding the financial toxicity has been an issue in the recent years where more and more research is showing this is a problem. And I think it is now getting to the front lines as far as clinicians, oncologists, their staff, their faculty are understanding that we need to be thinking about this as a problem. And that's one huge hurdle, at least identifying this as a problem and naming it. And, now, I think the next step for research is to start trying to intervene, trying to think of creative ways to do something about this. Are there apps? Are there financial navigation programs as we've mentioned-- social work, implementing social work earlier in the course, or having ways of identifying, you know, what a drug or combination therapy is going to cost for a patient and letting them know up front? You know, these are the options available if there are options, if there's multiple chemotherapy strategies or multiple nausea medicines that are out there that could work equally effective. Is there a way to then discuss that with patients in a way that says this may cause this? This may cost this. This is what this schedule looks like. You'll be coming in weekly versus bi-weekly. And this is what the drug costs and may affect your job or your work life and how your family might need to be helpful at certain times. And similar to the way we deal with other toxicities where we trade off if somebody has renal issues or other blood problems where certain treatments may not be the best idea for them, we think creatively about ways to get people the best treatment possible for them. And I think that's going to be a lot of the research in the next few years is looking at how can we intervene upon the problem of financial toxicity. And it's actually really exciting that this movement has taken off. We've now named the problem. It's become mainstream and gotten a lot more attention. And I think, now, the next step is for all of us in the research community and in the clinician community to start thinking about creative ways to help with the problem. Again, my guest today has been Dr. Ryan Nipp. Thank you for joining us. Thank you so much for the opportunity. It's always my pleasure. And to our listeners, thank you for tuning into the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate and review us on Apple podcast.
Nov 26, 2018
Mitigating Cognitive Effects of Chemotherapy and Radiation with Dr. Sara Hardy
Mitigating Cognitive Effects of Chemotherapy and Radiation with Dr. Sara Hardy Welcome to the ASCO Daily News Podcast. I'm Lauren Davis and joining me today is Dr. Sara Hardy, a resident in the Department of Radiation Oncology Medical Center and a neurologist in the University of Rochester. Dr. Hardy, welcome to the podcast.  Thank you for inviting me. I'm happy to be here. Today we're talking about cognitive dysfunction as it can happen in patients who receive both chemotherapy and radiation. How did you become interested in this side effect? As treatments have gotten better over the years, patients with cancer are just living longer and longer. And so cancer survivors are living with a lot of the symptoms from treatments that we're giving them. As a neurologist, I think I am especially sensitive to changes in cognition and other side effects that relate to cognition and neurology. I feel like cognition has a huge impact on quality of life. It impacts a survivor's ability to go back to work, survivor's ability to really go back to the life that they were living before. And I think it's an area where we can really have a huge impact. What areas of thinking and cognition are affected, and why? So it's a little different between chemotherapy-induced cognitive change and radiation-induced cognitive change. So for chemotherapy-induced cognitive change, there are deficits in memory, executive function, attention, and processing speed. These are higher level functions. They require a lot of different areas to work together. So it makes sense that these areas are affected. And then also, studies have shown that there is gray matter loss in the frontal and temporal lobes, which make sense-- this includes the hippocampus-- with chemotherapy. And there are changes in white matter integrity, and changes in white matter can affect processing speed. So a lot of it really makes a lot of sense when you look at the areas that are affected. Additionally, they've shown that chemotherapy can inhibit neurogenesis within the hippocampus. And so that may also have something to do with why a memory is affected. For radiation treatments, the most common thing that we see is probably verbal memory, so kind of that word-finding difficulty. And that's what was originally shown when they were looking at radiation for the whole brain. Additionally, they've shown that attention, executive function, and processing speed can also be affected. The effect on verbal memory is currently the target of a clinical trial. So they did a phase two clinical trial looking at changes in the radiation plan to avoid radiation dose to the hippocampus on both sides. And because that was a positive study, they've moved on to a phase three trial that we are now waiting on. How do other issues, including stress and sleeplessness from the worry of diagnosis and treatment, contribute to these issues? Stress can definitely make you more vulnerable, I'd say, to cognitive change in the setting of cancer and cancer treatment and really impact acutely your ability to perform a task. What I would say is that especially I think right after diagnosis, it has a lot to do with some of the changes that people complain of with forgetfulness and inattention. And then later on, I suspect that it has less to do with what we're seeing, but it definitely has an impact. That makes sense. Do you know any discrepancies between patient-reported outcomes of cognitive dysfunction and compared to objective results of testing? Yeah. So patient-reported outcomes are not always associated with our objective findings on neurocognitive testing. And these outcomes, the patient-reported outcomes, are sometimes more correlated with distress. And it's possible that our neurocognitive test is not picking up some of these subtle changes that people are seeing in their daily lives. It's also possible that people are compensating. One of my theories is that the people that are prone to notice these things, kind of young, healthy people, are able to compensate. And so it's hard for us to pick it up on neurocognitive testing, even though they know that they are trying harder. And as all people age, even those without cancer, we notice that we have that tip-of-the-tongue phenomenon, the characteristics of memory loss that happen more often than not. We know we want to say, but we can't quite convey the message. How do you differentiate between the natural progression of aging with other factors such as menopause or the onset of dementia with the cognitive effects of chemotherapy and/or radiation? Well, the good thing about the cognitive effects from chemotherapy and radiation is that they're often subtle. So they're not as severe as a frank dementia. To be diagnosed with dementia, it has to impact your ability to care for yourself, your ability to have personal hygiene or cook food, the activities of daily living. So thankfully, these are usually more subtle changes. But I think that there are a lot of things that contribute to these cognitive changes. Menopause is a time of life when people tend to complain more of forgetfulness, and there's some evidence that hormonal therapy in breast cancer patients can also cause some cognitive changes. Natural aging causes some subtle cognitive changes and some atrophy that we see on imaging. So really, there are a lot of factors that contribute to this very complex process that we refer to as cognition and that we try to break into different domains. So I'd say that, in general, this is a very complex area with a lot of factors that are leading to changes in cognition. And thankfully, we're just seeing kind of these subtleties, rather than people who because of their care are not able to care for themselves. How are people able to bounce back from cognitive effects of chemotherapy and radiation? Are there long-term effects and short-term effects that can be improved upon? Yeah. So especially in the chemotherapy trials, we have more long-term data. And really, you're looking at about a third of patients who do not improve over time. They say about 75% of patients have acute cognitive changes when they're being treated, and then that goes down to about 30% or so as you get further and further out. So we're trying to identify those patients and trying to help them improve, much the way the others did. And there are several different options in order to help patients to improve their cognitive training, and that's where you focus on a particular cognitive domain. And they work. They sometimes play games to try and target that area. There's cognitive rehab, which allows you to find ways to work around the deficits so that you can do what you want to in your daily life. And also, exercise has been shown to really improve cognition. So especially executive function improves if you hit a certain target level of activity. For radiation therapy, there's definitely some evidence that some patients are more affected than others. But we are still working to find ways to identify who is going to remain vulnerable, who is not going to improve, and who we really need to target. OK. That's great to know. So I'm curious. How do you help educate others in the oncology field to look for and mitigate symptoms? I think we're lucky here because we have a survivorship course at University of Rochester for both the medical oncology fellows and for the radiation oncology residents. And one of those classes is entirely devoted to cognitive changes in cancer survivors on both patients with brain tumors and those with tumors elsewhere in the body. And I think that does a lot to help people learn about this early on in their training. Additionally, this year at ASCO, there was a panel where several of the leaders in the field, including my research mentor, Michelle Janelsins, discussed cognitive changes in cancer survivors, which was great. Additionally, I've been doing some lectures, so I do some lectures for the neurology residents on some of the neurologic complications we see in cancer survivors and then also for my co-residents in the radiation oncology department. That's great. Again, today, my guest has been Dr. Sara Hardy. Thank you for joining us. Thank you for having me.  And to our listeners, thank you for tuning in to the ASCO Daily News Podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcast.    
Nov 02, 2018
ASCO Quality Care Symposium: Key Takeaways from the Meeting with Ethan Basch, MD
ASCO Daily News Podcast Title: ASCO Quality Care Symposium: Key Takeaways from the Meeting with Ethan Basch, MD Welcome to the ASCO Daily News Podcast. I'm Lauren Davis. And joining me today is Dr. Ethan Basch of the University of North Carolina. He's both a medical oncologist and a health services researcher. Dr. Basch has clinical expertise in prostate cancer. And his research includes patient-reported outcomes, drug regulatory policy, and comparative effectiveness research. Dr. Basch, welcome to the podcast. Nice to be here. So you've just returned from the Quality Cancer Symposium. How was this event different from previous years? The symposium this year was really superb. It was very well attended by a mix of quality officers, clinicians, and researchers. And to me, what was really striking about this year's meeting is that people are really doing applied projects that are multidisciplinary. And what I mean by this is that, in prior years, we'd see very small pilot projects in very narrow areas. We would see projects that maybe were being done just by researchers or projects just being done by community clinicians. But what we're really seeing now is this coming together of research and practice with a focus on value-based care. And the projects that are being done are very sophisticated and are spanning the continuum from identifying a problem in practice to developing a quality project to measuring and then modifying the outcomes. And so that's really a very exciting development, where we see the research and practice coming together. What would you say are some of the take-home messages about innovations in care delivery that resonated with you or folks that you spoke with? I'd say the biggest message from the meeting this year is, it can be done. When there are quality projects that focus around some of the value-based care topics that have risen to the top at this meeting, it was very clear that it is feasible to set up programs and to enlist stakeholders and to actually execute in these areas. For example, there were projects focused around financial toxicity and counseling, around reducing low quality treatment, around navigation, coordination of care, unnecessary ER visits and hospitalizations. And in all of these areas, there was the ability to gather data, develop programs, implement those programs, and collect data. So it could be done. I think the other take-home message is that there is an increasing number of quality roles in health systems for using data. It used to be that these kinds of roles around value-based care delivery and quality were maybe performed by those who were doing other functions within an organization. And there are an increasing number of dedicated personnel for carrying on this work. Financial toxicity, you just touched on, affects all aspects of cancer care. Are there areas where quality of care is improving despite costs of treatments and services? So I think that that's a challenging question to answer, because it is a heterogeneous landscape. I mean, certainly, there are areas where quality continues to improve that's disconnected from cost. But what's clear is that it's becoming harder and harder to devote resources to improving quality of care when cost is going up. And of course, when we think about value, value is quality over cost. And so as your cost increases, you have to improve quality that much more in order to provide value. There were interesting data presented at the meeting showing that more than half of patients with cancer experience substantial financial distress that affects their decisions and compliance, their workplace, and the way that they conduct their lives. And there were practical examples of financial navigation programs that can be integrated into practices to help patients, both to deal with their financial situations and also to deal with their distress that they feel due to financial pressures. However, it's pretty clear from the evidence that was provided that if costs do not start to become contained, it will become not only difficult to continue to be able to devote resources to quality-- because the resources will be going elsewhere-- but it will be very difficult to help patients to manage their own distress or to ensure that people will be compliant with treatments that require increasing out-of-pocket costs. Absolutely. In your clinical experience with patients who have cancer, do you think people speak up enough about their needs and expectations? So unfortunately, research has shown that we, as providers, remain unaware of many of the needs and expectations of our patients. There actually was terrific work from a group in Canada presented at the meeting, at the Quality Symposium, presenting some new quality metrics around patient-centeredness that moved beyond our typical patient satisfaction or patient experiential questionnaires that many of our hospital systems use. And these metrics look at the extent to which patients feel that their needs and their expectations are being understood and acted upon by care teams. And they found, actually, quite a bit of variability between practices. And they are now intervening at individual practice levels in order to try to see if enhanced navigation services can improve that dimension of care delivery. That's great. So in our modern age, we have so many communication devices and apps at our hands. But what would you say is the best way to find out how patients are doing and experiencing treatment? Well, there's a lot of interest in patient-reported outcomes and other electronic communication approaches that can connect practices to patients. As I alluded to in the prior question, it's very common that the practices aren't aware of how patients are feeling, either their side effects of treatment or other symptoms related to disease. And these are missed up to half the time. And so this is a big opportunity. At this point, I think it's unclear what approach is going to prevail in the end. Will this be part of the patient portal that people can download onto their smart device? Will this be standalone programs that can then send messages to providers? I think it's very early in the days of these kinds of technologies. But I think that what's exciting is that so many patients are using various kinds of devices to track themselves or to communicate with providers. And I think what we'll see in the years ahead is practices and health systems capitalizing upon this Fitbit culture in order to harness that information for clinical care. But again, I think we're really in early days of this movement.   That's great. Again, my guest today has been Dr. Ethan Basch. Thank you for joining us. Thank you. I would just like to thank my colleagues, who were instrumental in putting the meeting together, including my colleague, Dr. Monika Krzyzanowska, who was this meeting's chair-- this year's meeting chair-- Dr. Michael Neuss, who was last year's chair. And the two of them were really key to putting together the agenda, as well as our entire group for planning. But I'd also like to thank Carli Gurtshaw and Tony Schweizer at ASCO, who were the staff members who really brought the whole meeting together. And to our listeners, thank you for tuning in to the ASCO Daily News Podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcasts.  
Oct 18, 2018
Assessing Value and Outcomes in Older Adults with Cancer: Erika E. Ramsdale, MD
  Welcome to the ASCO Daily News podcast. I'm Lauren Davis, and joining me today is Dr. Erika Ramsdale, a board certified specialist in geriatric medicine and medical oncology at the University of Rochester Medical Center. Dr. Ramsdale, welcome to the podcast. Thank you so much for having me. So advancing age is the largest risk factor for cancer overall. One quarter of new cases are diagnosed in people aged 65 to 74 years, yet many oncologists do not have geriatric training. Could you walk me through a geriatric assessment? How long does one take? Sure, so a geriatric assessment looks at an older adult's functioning from a lot of different perspectives. So for example, physical, emotional, social, nutritional, and cognitive functioning, and it also typically includes an assessment of the health problems that the person might have and medication burden, or what we call polypharmacy. Geriatric assessment uses a set of validated tools that you can combine in various ways, depending on the time you have and the resources you have available. I would say, ideally it's delivered in a multidisciplinary setting with input not only from the geriatrician but also nurses, social workers, physical, occupational therapists, pharmacists, nutritionists, and other team members. And you can do a geriatric assessment-- sort of a mini geriatric assessment, I should say-- in as little as a few minutes, just do some screening questions and things like that, but a more extensive evaluation could take 30 to 45 minutes or sometimes even longer. So here at the University of Rochester, we have a multi-disciplinary geriatric oncology clinic, where our oncology colleagues can refer patients for geriatric assessments and targeted recommendations, and we actually do a pretty lengthy assessment within that clinic. So we have one of the largest programs here, but these sorts of clinics are showing up at a lot of other centers as well across the country. That's great. And geriatric assessment is now-- yeah, it's pretty exciting. Geriatric assessment is now part of the ASCO guidelines for all older cancer patients who are going to receive cancer therapy. So if you look in those guidelines, there's also some guidance about initial screening questions that can help the oncologist determine who needs more extensive evaluation, for example, in a [? geriant ?] clinic, and this can help busy oncologists sort of streamline their daily workflow. That's great. It sounds very comprehensive. So I'm wondering, how do you measure quality of care and quality of life in this patient populations? And also, what is known about patient reported outcomes in older patients? Quality of care and quality of life seem like they're pretty tightly intertwined concepts, but I think they're talked about quite differently in the literature. So quality of care, when I read about quality of care in the literature, this deals with following guidelines and using evidence-based care. But what we have to remember is that for older adults, we don't have necessarily as much evidence. The evidence available is usually obtained from younger adults, and it may not be generalizable or applicable to older adults. But quality of care measures are really trying to standardize a process for selecting the next right step, and so this is more of an algorithmic way of thinking in a lot of cases. Quality of life, on the other hand, is obviously very subjective, and it does not mean a standardized thing. You can't apply an algorithm to tell you what's important to someone or how you should modify their treatment based on that. So I think it's a very different type of thinking. I think you have to create a story about what is important to patients and how your recommendations will fit with what they prioritize. So this is kind of more narrative thinking. It's very hard to do, I think. It takes experience, it takes talking to the patient, and it takes doing a broad assessment like the geriatric assessment. So the patient reported outcome sort of fit into and are part of that story, looking at how are they feeling and how are they functioning at home. Good point. How do you communicate prognosis and treatment plans to caregivers and adult children? Again, this is a learning process, but personally my experience has been that patients and caregivers also prefer direct and straightforward communication about prognosis. I think it's always important to ask what they want to know because some patients and caregivers will want to know more details, and more numbers, more statistics, and some will want less of that. But when you're communicating about treatment options, I also think you have to strike a balance between just giving patients a recommendation, telling them what you think they should do on one hand, and then on the other hand is an information dump where you just give them all the options and tell them to make a choice. So I see my role as the experienced advisor. I give them the information on all the treatment options, but I also interpret them in light of the patient's story, and I recommend things based on their lives, their preferences, and also what we get from the geriatric assessment that may tell me what they're likely to handle treatment-wise. So let's talk about cost of care. By the year 2020, the annual cost to treat cancer in the United States is projected to rise to 173 billion. This means that older adults with cancer will face increasingly high costs for needed medical care. In the wake of ever increasing costs, how do you communicate to patients the value of treatment when they face a financial burden? I think this is a really tough one because I think most physicians, and myself included in that, are still pretty unaware of the cost differentials between different treatment options. And I think whether or not cost consideration should even come into play with how we recommend therapies is a tricky ethical question, and it's open to debate. So I feel on safer ground talking about value which is a broader concept that fits into what we were sort of talking about before, which is quality of life and what someone wants for herself. So value is more about outcomes and what we get out of whatever decisions we make, and the outcomes that we've traditionally been most focused on are things like how long someone lives and survival outcomes. I think, for older adults, we know this is often not their priority. They may prioritize, instead of living a long time-- they prioritize remaining independent in their own home, for example, or preserving dignity, or avoiding severe side effects from treatment. And what we also know is that talking about what people want for themselves throughout their treatment course, and starting these conversations really early, leads organically to decisions that tend to both improve the outcomes that people care most about and also to save money. So to give you an example, most people don't want to be hospitalized at the end of their lives or go through really heroic measures that may not help them achieve their goals, but this is often what happens when there's not a lot of upfront discussion and advanced planning. Yes. So I think we do need to know more about how we make decisions, effects, costs, and also value. And one of my main research interests is informatics implementation and these decision support tools for older adults with cancer, so I've taken the geriatric assessment and built it into our electronic medical records so it's integrated. And we can start streamlining data capture, and then looking at geriatric assessment, how it changes over time, and linking it with outcomes in unique ways within this, you know, EMR within the database. I think we need to go beyond just survival metrics, and look at other measures of value, and what patients say is worthwhile to them. In addition to cost, we are anticipating a silver tsunami of older people with cancer. Are there enough oncologists to treat patients, or is there still a shortage? I think, you know, all the numbers I've seen have indicated that there's a severe shortage not only of geriatricians and things like that but oncologists also. So as I mentioned before, ASCO guidelines are now recommending geriatric assessment for all adults older than 65 who are going to receive some sort of cancer therapy because we know that the standard oncologic assessment can miss things that are a part of the older adults' story. But I think there are some problems actually delivering on this because oncologists are in shortage. They're already overburdened, and very many of them likely don't have the time, and space, resources to do at least a full geriatric assessment on every patient who needs one. And I think there's also the question, once you have this data, what do you do with it? You need some expertise to fit this information into the treatment and recommendations, and I think this is true even if you're an oncologist very used to seeing and treating older adults. So this is one of the main reasons I'm looking at EMR-integrated decision support to help when an oncologist may not have geriatrician available. And so I think also you need not only physician resources but other medical team resources. So if something comes up, an issue is found by the geriatric assessment, you may need other resources. We can't think just in terms of cancer treatment like chemo. We may need physical therapy. We may need social work. We may need cognitive rehabilitation, pharmacist counseling, and I think there's really a shortage of those resources as well. So let's talk about clinical trials for a moment. Age is a factor for clinical trial participation. Do you think we've moved the needle on this in recent years? I hope so. I think awareness is growing that we need to enroll more older patients and get more data, but I think older adults are still very under-represented in clinical trials. So I think the awareness is causing people to question putting in an age cut-off into clinical trial eligibility, but I think frailty is still a big issue because those who do get enrolled, if they're older, are the fittest of the fit. And so a lot of us are advocating for more clinical trials for the more frail patients, and I don't think the needle has moved as much on this. I'd say it's a really complex problem. Our gold standard is a randomized clinical trial, but this is really a problem on several levels in an older, frailer population. It's really hard to randomize patients when they're-- you know, older adults are so different in so many different ways, and this makes it really hard to interpret the statistical data. There's a lot of confounding aspects to looking at data that you get. So my personal opinion is we may have to really look at more novel trial designs, look at new statistical methods, and sort of incorporate big data sets, things like that to look at the data in new ways. But bottom line, we need to keep drumming up awareness that there are still so many knowledge gaps when it comes to how to treat and how to follow an older adult with cancer. And the last point I'd say, there are some phenomenal patient advocates that I've worked with who are also critical to moving the needle on this. That's great. And as an expert in this field, what are some key takeaways that you would suggest for oncologists who are treating older patients with cancer? Yeah, so I actually had the opportunity to talk to a number of oncologists across the country. I did some interviews with them. So I asked them about their approach to assessing older adults, what they think about the geriatric assessment, what resources they might need, some questions like that. And what surprised me the most, I think, is that a lot of them were still not convinced that geriatric assessment was necessary or would add anything for their care of older adults. So I think there's still a pretty prevalent belief that-- you know, and indeed these oncologists see a lot of older cancer patients. They're the biggest population that we see, and I think there's a sense that I know frailty when I see it, and that this so-called eyeball test is all that is needed. And so I would personally like to increase awareness that the geriatric assessment is important and really is worth the time to do. It will uncover things that are really otherwise invisible during the standard assessment, and certainly to the eyeball test. So I think the other takeaway based on what we've talked about is to start talking to your patients about preferences and quality of life at the first visit and keep on talking about it. Something that one of my mentors said that has really stuck with me is that people don't want to know how long they have to live. They want to know what exactly is going to happen to them. And I've found this to be particularly true for my older patients. I would say on average they care more about symptoms, independence, dignity, all the things that go into quality of life, and they care more about than they do their life expectancy. So it's the story, and it really guides how I treat them and interact with them. So just to close with an example, I had a patient recently whose main goal was to stay in her home, and it was to take care of her elderly dog at the end of his life. And we talked through it, and we actually decided not to do a more aggressive treatment regimen because I thought, and we discussed, that it would probably hasten her move to an assisted living facility, and she would have to give up her dog. So we did a potentially less effective regimen against her cancer, but one that was much, much less toxic and would allow her to live out her goal, and she was she was happy with that choice. Again, my guest has been Dr. Erika Ramsdale from the University of Rochester Medical Center. Thank you so much, Dr. Ramsdale for your time today. Well, thank you for the opportunity to talk to your listeners. And to our listeners, thank you for tuning in to the ASCO Daily News podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple podcast.  
Sep 27, 2018
Remaining an Independent Practice in the Era of Consolidation: Harvey Bichkoff, MPH
  Welcome to the ASCO Daily News podcast. I'm Lauren Davis, and joining me today is Harvey Bichkoff, CEO of Marin Cancer Care in California. Mr. Bichkoff has been an administrator at both public and private hospitals for many years before joining this integrated center that provides cancer care with compassion. In this podcast we will discuss the challenges for oncology practices to remain independent in the era of consolidation. Mr. Bichkoff, welcome to the podcast. Thanks very much, Lauren. It's an honor to be here and talk about this important topic. The 2016 Community Oncology Practice Impact Report shows that since 2008 nearly 1,600 community practices and/or clinics nationally have been affected by closings, hospital acquisitions, and corporate mergers. This is a rate of 15.1 community practices affected per month. What are some of the reasons for this increase? It's been a real challenge for independent practices to maintain their operations over the last few years. There is tremendous pressure from hospitals that are trying to acquire oncology practices. They're doing this to subsidize other acquisitions that they've made and losses from their operations. Some hospitals give significant drug discounts from something called 340B pricing, they often have better commercial contracts, and sometimes have medical foundations that are made up of most of the referring specialists and primary care doctors. Also, some oncology groups have seen declines in their reimbursement, maybe due to changes in peer mix, or more Medicare patients, as well as increases in their overhead costs. These factors may lead to selling to a hospital, and lock in or maybe increase the physician's income for a few years. There are risks to giving up autonomy to the hospitals. Physicians may not be able to spend as much time with their patients, they lose control over staffing decisions, and their income guarantees are often short-term, and have to be renegotiated after they've lost leverage. They may also lose some key employees. The new hospital employer may reduce employee salaries and benefits which could result in turnover. Finally, new acquired oncology practices may feel lost in a larger system where the emphasis may be on growth of market share and profits rather than patient, employee, and doctor satisfaction. Consolidation seems to be a trend in cancer care, but what are some of the benefits for private practices to remain independent? The primary advantages of remaining independent is that doctors have more control over their time spent with patients, employee hiring and firing decisions, and control over their budget. Some commercial peers are starting to realize that it is beneficial to pay independent doctors more so that they can remain independent, versus paying the hospitals who charge a great deal more for the same services. I've also heard from colleagues around the country that it can be extremely difficult to renegotiate their salaries after the initial term. If the hospital is not doing as well financially it could impact the group. They can also experience reductions in benefits and retirement contributions. Once the practice is sold it is competing with other hospital departments for their budget. Other significant advantages are the ability to make quick policy and process decisions. Hospitals are much more bureaucratic and often have several layers of management, which can stall decision-making. Despite the increasing wave of acquisitions by larger practices or by hospitals, many established private practices wish to remain so. What are some of the challenges to do that? As you said, the consolidation of medical groups, as driven by hospitals, health care systems and academic centers, has made it very tough on independent practices. Also the aging of the population and increases in Medicare patients where we are lucky to break even is much more difficult. Our market is also somewhat unique. We have a good peer mix, but extremely high housing costs. This makes it difficult to recruit locally, as unemployment is very low and people can't afford to live here. There are also projected shortages of oncologists and oncology nurses. Lately we've had a hard time finding experienced oncology nurses, and we've had to train our new nurses with less experience. Another significant challenge, which is particularly worse in cancer, is burnout. We've worked with an expert in the field who's talked with both our staff and doctors about techniques to increase resiliency. Are there specific ways to be cost effective and keep practice costs down? Our biggest costs are drugs, staff, and rent. We monitor costs and cash flow carefully. The doctors and the management team regularly meet, and everyone is engaged. We also watch our drug costs carefully, and have our distributors match prices when better pricing is available on the market. We also buy extra drugs when cash pemits before the manufacturer increases prices. Finally, we bid out our drug and supply costs every couple of years to make sure the pricing is competitive. As far as rent goes, we locked in a long-term lease so we know our future costs. And in some instances, you are able to also negotiate tenant improvement allowances on rental deals. As it relates to staffing, we are members of ASCO's PracticeNET. We benchmark our practice against other oncology groups. We found that we are efficient but higher cost. We invest in our employees, and have lower turnover, and outstanding patient satisfaction results. We are in a high-cost area, but believe we should pay a premium because working in cancer is tougher than other specialties. We also cross-train our staff to cover sick days and vacations. We're very fortunate to have great and committed a team of employees. Marin Cancer Care offers integrative medicine, everything from acupuncture to music therapy. What's your secret, especially considering that integrative medicine is both desirable and in demand. How can practices offer these options while still doing more with less? That's a good question, Lauren, and it's been a challenge for us. We started a integrated program in our practice over 20 years ago, as one of our physicians had a passion for these services based on his own personal experience. He's since retired, and one of our new physicians, who also has a commitment to the program, has allowed it to continue to grow and prosper. I think the most important element is having a physician that is committed to these programs. Over the past several years we've had a co-management agreement with our hospital. They pay us for administrative time, and to run the integrative and cancer program overall. The hospital has been extremely committed to the integrative medicine program. They've hired several navigators in the areas of breast, prostate, GI, and survivorship. They've supported the lung cancer screening program. And recently hired palliative care physicians and mid-level providers. It will be very difficult for us to do this on our own, and have a robust integrated program without the hospital support. Absolutely. What are some key steps for private practices to innovate and survive? I think the primary way to innovate and survive is to always put the patients and their families first. We hire staff who are genuinely interested in customer service, and clinicians who are focused on patient-centered care. We have an excellent reputation for quality and good relations with the local academic medical centers. We were the first practice to join ASCO's CancerLinQ, and are accredited by a national organization, the AAAHC. We're always involved in multiple quality initiatives on how to improve patient care. Our practice has also invested in an experienced management team. It seems like most successful practices have made that investment. We talked a little bit about the cost side minutes ago. It may be even more important to talk about the revenue side. We are paid fairly well by our commercial carriers, and we look at them as partners. We know many of the medical directors who vouch for our quality after analyzing our cost data, and they're willing to pay us more based on our evidence-based practice of medicine. This is extremely important as costs rise and the markets get more competitive. Finally, it's not easy to turn back once you've sold. It is costly to create a work force, and difficult to renegotiate commercial contracts. Some doctors are biting the bullet and starting over due to their dissatisfaction with their hospital partners. Thank you so much. Again, my guest today has been Mr. Harvey Bichkoff. Thank you for joining us. Thanks for the opportunity, Lauren. I hope it's helpful to other independent practices.  Thank you. And to our listeners, thank you for tuning in to the ASCO Daily News podcast. If you're enjoying the content we encourage you to rate us and review us on Apple podcast.
Sep 21, 2018
ASCO18 Takeaways: Dr. John Sweetenham
Editor-in-Chief of the ASCO Daily News John Sweetenham, MD, FRCP, FASCO, discusses the practice-changing science presented at the 2018 ASCO Annual Meeting. 
Jun 04, 2018
Triple-Negative Breast Cancer: Dr. Heather L. McArthur
Heather L. McArthur, MD, MPH, of Cedars Sinai Medical Center, discusses advances in the treatment landscape for patients with triple-negative breast cancer. 
May 30, 2018
Anxiety or Depression in Patients With Cancer: Dr. Barbara L. Andersen and Dr. Marlena M. Ryba
Babara L. Andersen, PhD, of Ohio State University, and Marlena M. Ryba, PhD, of Coastal Carolina University, discuss recognizing, assessing, referring, and monitoring patients with cancer experiencing moderate to severe anxiety or depression symptoms. 
May 25, 2018
Sarcoma: Dr. William D. Tap, Part II
In part two of this two-part podcast, William D. Tap, MD, of Memorial Sloan Kettering Cancer Center, continues his discussion of new advances in treating patients with sarcoma.   
May 21, 2018
Sarcoma: Dr. William D. Tap, Part I
In part one of this two-part podcast, William D. Tap, MD, of Memorial Sloan Kettering Cancer Center, discusses new advances in treating patients with sarcoma. 
May 21, 2018
Gastrointestinal Cancers: Dr. Ramesh K. Ramanathan
Ramesh K. Ramanathan, MD, of the Mayo Clinic Cancer Center, Phoenix Campus, discusses new advances in treating patients with pancreatic cancer.
May 14, 2018
Genitourinary Cancers: Dr. Adam P. Dicker
Adam P. Dicker, MD, PhD, of the Thomas Jefferson University Sidney Kimmel Cancer Center, walks us through the debate about the value of local treatment for newly diagnosed metastatic prostate cancer. 
Feb 01, 2018
Immuno-Oncology: Dr. Seth M. Pollack
Seth M. Pollack, MD, of the Fred Hutchinson Cancer Research Center, discusses immunotherapy for sarcoma and how varying microenvironments in sarcoma subtypes impact response to immunotherapy.
Jan 22, 2018
Gastrointestinal Cancers: Dr. Nataliya V. Uboha
Nataliya V. Uboha, MD, PhD, of the University of Wisconsin’s Carbone Cancer Center, discusses the immunotherapy agents on the rise for treating esophageal cancers.
Jan 17, 2018
Lung Cancer: ASCO 2017
Nathan A. Pennell, MD, PhD, discusses notable lung cancer abstracts from the 2017 ASCO Annual Meeting.
May 30, 2017
Patient and Survivor Care: ASCO 2017
In this podcast from the ASCO Educational Book, Don S. Dizon, MD, FACP, interviews Dr. Mary Sabatini, MD, PhD, about pertinent health issues for women with BRCA mutations.
May 24, 2017
Radiation Oncology: ASCO 2017
Experts recap key takeaways from the SWOG Spring Group Meeting.
May 24, 2017
Hematologic Cancers: ASCO 2017
ASCO Daily News Editor-in-Chief John Sweetenham, MD, FRCP, FACP, discusses notable hematology abstracts from the 2017 ASCO Annual Meeting.
May 24, 2017
Immunotherapy: ASCO 2017
Roy S. Herbst, MD, PhD, provides updates on immunotherapy for cancer treatment.
May 24, 2017
Prostate Cancer: ASCO 2017
Steven E. Finkelstein, MD, discusses the latest recommendations from the prostate cancer RADAR II Working Group.
May 24, 2017
Sarcoma: ASCO 2017
George D. Demetri, MD, discusses the evolving treatment landscape of advanced soft tissue sarcoma.
May 24, 2017
Gynecologic Cancers: ASCO 2017
Susana M. Campos, MD, MPH, provides an update on PARP inhibitors for ovarian cancer.
May 24, 2017
Immuno-Oncology: Dr. Catherine Lai
Dr. Catherine Lai, of the National Heart, Lung, and Blood Institute at the National Institutes of Health, discusses new immunotherapies aimed at decreasing relapse rates in patients with leukemia.
Feb 23, 2017
Immuno-Oncology: Dr. Heather McArthur
Dr. Heather McArthur, medical director of breast oncology at Cedars-Sinai Medical Center, discusses combination radiotherapy/immunotherapy treatments aimed at increasing survival outcomes of patients with breast cancer that has metastasized to the brain.
Feb 23, 2017
GU Cancers: Dr. Tito Fojo
Dr. Tito Fojo discusses the treatment of adrenocortical cancer in adult and pediatric patients with the disease.
Feb 08, 2017