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ASCO Daily News

ASCO Daily News

By: American Society of Clinical Oncology (ASCO)
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The ASCO Daily News podcast features engaging discussions with leading oncologists on timely topics in oncology, hosted by Dr. Monty Pal.All rights reserved Hygiene & Healthy Living Physical Illness & Disease
Episodes
  • The Emergence of Triplet Therapies in ccRCC in the Frontline Setting

    The Emergence of Triplet Therapies in ccRCC in the Frontline Setting
    Jul 13 2023
    Drs. Pedro Barata and Naomi Haas discuss the emergence of clinical trials investigating triplet combinations in advanced renal cell carcinoma, factors that influence treatment decisions, strategies to personalize therapies in the frontline setting, including response-adaptive treatment strategies, and the use of biomarkers such as gene expression analysis to guide initial therapy. TRANSCRIPT Dr. Pedro Barata: Hello, I'm Dr. Pedro Barata. I'm your guest host of the ASCO Daily News Podcast today. I'm an associate professor of medicine and also a GU medical oncologist at University Hospital Seidman Cancer Center, Case Western University in Cleveland, Ohio. I'm also an associate editor for the ASCO Educational Book. Today I'm really delighted to welcome Dr. Naomi Haas, the director of the Prostate and Kidney Cancer Program at the Abramson Cancer Center and professor of medicine at the University of Pennsylvania.  Welcome, Dr. Haas. Dr. Naomi Haas: Thank you, Dr. Barata. It's a pleasure to be interviewed. Dr. Pedro Barata: Thank you. As you know, we've seen significant strides in the frontline treatment for patients with advanced clear cell renal cell carcinoma (RCC), and there are multiple doublet regimens that are now the standard of care for those patients. The goal for us to chat today is to discuss the emergence of clinical trials that are really investigating triple combinations and the factors that influence treatment decisions around triplet combinations for patients with advanced renal cell carcinoma. I want to congratulate you for the great work that you did in a recently published article in the 2023 ASCO Educational Book. So thank you for your contributions. And just before we get started, I just want to highlight that our full disclosures are available in the transcript of this episode. So, Dr. Haas, again, it’s great to have you. Thank you for taking the time. Let me get started. So, we know that there are multiple standard of care doublet regimens, all of them immunotherapy-based combos, and they usually include 1 checkpoint inhibitor or 2, such as ipilimumab plus nivolumab or a combination of an immune checkpoint inhibitor with a VEGF TKI. And we have a number of examples like that. Can you tell us about the trials that have emerged exploring triplet therapies in the first-line setting for patients with advanced RCC? Dr. Naomi Haas: Sure, and I'm going to focus just on triplet therapies that are just about ready to go. But as you know, Pedro, there are probably many different combinations that we'll see in the future. Some of the combinations that have already been conducted as clinical trials include combinations of VEGF receptor tyrosine kinase inhibitors along with immune checkpoint inhibitors. I'll highlight one which was batiraxcept plus cabozantinib and nivolumab, and it's a combination of VEGF inhibitor, immune checkpoint inhibitor, and also an AXL inhibitor. So, most of these capitalize on other vulnerabilities with renal cell carcinoma.  So, as you said, they build on the tyrosine kinase inhibitor pathway or on the immune checkpoint inhibitor pathway. Some of them are combining drugs such as CDK inhibitors. There was axitinib plus nivolumab plus palbociclib trial that is getting ready to launch. Others are combining the use of belzutifan, which is a HIF inhibitor in combination with VEGF inhibitor and immune checkpoint inhibitor. There are a couple of those that are ongoing, one of them looking at combinations with lenvatinib. And I think there are also trials getting ready to launch that are using it in combination with cabozantinib and nivolumab.  Additionally, another very interesting direction is trying to affect the gut microbiome. And there was a clinical trial presented by Dr. Monty Pal at the gut microbiome session at ASCO, which combined CBM-588, which is a probiotic, in combination with cabozantinib and nivolumab. And that showed an improvement in progression-free survival compared to the combination of cabozantinib and nivolumab alone. And previously there was work published using CBM-588 in combination with ipilimumab and nivolumab. So that's an area of high interest to patients. But most of these combinations capitalize on either vulnerabilities, signs of resistance in pathways or in adding other pathways that have previously been unaddressed in renal cell carcinoma, and are combined with pathways that we know are effective. Dr. Pedro Barata: Wow, that's a fantastic overview of some of the approaches being considered in the frontline, so thank you for that. And actually to your point, some of them we've seen some data, others more later stages of development. So with that in mind, we also know that we have on one side of the story we have how much of these combos of triplets can actually be effective and help patients. From the other perspective is about tolerability, treatment options, and patient health. They're both very important considerations.  Can you tell...
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    23 mins
  • THOR, CONTACT-03, and Other Advances in GU Cancers at ASCO23

    THOR, CONTACT-03, and Other Advances in GU Cancers at ASCO23
    Jun 27 2023
    Drs. Rana McKay and Jonathan Rosenberg highlight key advances in genitourinary cancers featured at the 2023 ASCO Annual Meeting, including the THOR study in mUCC, VESPER in muscle-invasive bladder cancer, CONTACT-03 in mRCC, and TALAPRO-2 in mCRPC. TRANSCRIPT  Dr. Rana McKay: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Rana McKay, your guest host for the podcast today. I'm a GU medical oncologist at the Morris Cancer Center at the University of California in San Diego and an associate professor at the University of California in San Diego School of Medicine. Joining me today is Dr. Jonathan Rosenberg, the chief of the Genitourinary Oncology Service at the Memorial Sloan Kettering Cancer Center in New York. We'll be discussing practice-changing studies and other key advances in genitourinary cancers that were featured at the 2023 ASCO Annual Meeting.   You'll find our full disclosures in the transcript of this episode, and disclosures of all guests featured on the ASCO Daily News Podcast are available on our transcripts at asco.org/DNpod.  Jonathan, it's great to have you with us today. How are you?  Dr. Jonathan Rosenberg: I'm doing very well. Thanks so much for hosting today.  Dr. Rana McKay: Oh, of course. It's always fun to step back from ASCO and reflect on all the practice-changing and practice-informing studies that were presented.  Dr. Jonathan Rosenberg: Absolutely.  Dr. Rana McKay: Maybe we can dive right in with LBA4619. This is the much-talked-about THOR study of erdafitinib versus chemotherapy in patients with advanced or metastatic urothelial cancer with select FGFR alterations. What are your key takeaways from this study?  Dr. Jonathan Rosenberg: It is indeed a study we've been waiting for, for quite some time, to see the results in the confirmatory study after the accelerated approval of erdafitinib. This is half of the THOR trial. There were 2 cohorts of patients. One cohort were patients who previously received a checkpoint inhibitor randomized to chemotherapy or erdafitinib, and those data were reported at ASCO this year. The other cohort was randomized against a checkpoint inhibitor in patients who have not received a checkpoint inhibitor, and we'll see those data in a future meeting.   The bottom line for the THOR study is that FGFR3 inhibition improved overall survival compared with chemotherapy, and the chemotherapy in this study was a taxane. The overall survival was 12.1 months for erdafitinib compared to 7.8 months for chemotherapy with a hazard ratio of 0.64. This led to the DMC to stop the study and blind the data and cross people over. There was also a PFS advantage. There really weren't a lot of new toxicity signals seen; the usual suspects in terms of mucositis, hyperphosphatemia, diarrhea, dry mouth, and onycholysis.  And so, what it tells us ultimately is that in a patient who's progressed on a checkpoint inhibitor, we can feel comfortable about using erdafitinib knowing it provides a survival advantage in patients who've been previously treated for advanced urothelial cancer and have an FGFR alteration, either an FGFR2 or 3. And hopefully, we'll see more data in the future from the study, maybe not too long in the future from the other part of the study, comparing it to checkpoint inhibition.   Dr. Rana McKay: That's really exciting. I think it's exciting to see the data about the positivity of erdafitinib versus chemotherapy in this context. Looking at the phase 3 data is going to be really important. Looking at the data in the IO naive context is going to be really important. I feel like this sort of reaffirms what we've been doing in clinical practice. But how do you feel that the study is practice-changing?   Dr. Jonathan Rosenberg: I think it gives us reassurance that for these patients, erdafitinib is an appropriate option. There's no randomized data between erdafitinib and other choices, such as sacituzumab, which is also based on an accelerated approval, or enfortumab, which is based on randomized phase 3 trial. But it gives us level-1 evidence. I do wonder whether the comparison against the checkpoint inhibitor may turn out differently, but we'll see. Those data aren’t in evidence. And I do think it was interesting that the majority of patients who were enrolled on the trial were PDL-1 low. We'll see what the comparison to a checkpoint inhibitor is like and whether those patients have similar characteristics.  Dr. Rana McKay: Yeah, you're almost kind of selecting for people that were not primed to respond.   Dr. Jonathan Rosenberg: Exactly.   Dr. Rana McKay: Well, that's really exciting, I think. Moving on to localized bladder cancer, Dr. Pfister presented the results of the VESPER trial. That's LBA4507. I think this study was really important. This was a trial that explored dose-dense MVAC with methotrexate, vinblastine, doxorubicin, and cisplatin or gemcitabine-cisplatin as a perioperative ...
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    23 mins
  • Spotlight on Immunotherapy at ASCO23

    Spotlight on Immunotherapy at ASCO23
    Jun 26 2023
        Drs. Diwakar Davar and Jason Luke discuss KEYNOTE-716, KEYNOTE-942, RELATIVITY-047, and other key advances in melanoma, including the promise of mRNA vaccines in melanoma and potentially other cancers, as well exciting advances in neoadjuvant therapies across malignancies featured at the 2023 ASCO Annual Meeting. TRANSCRIPT  Dr. Diwakar Davar: Hello, and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Diwakar Davar. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh Hillman Cancer Center. I'm delighted to have my colleague and good friend Dr. Jason Luke on the podcast today to discuss some practice-changing studies and other advances in immunotherapy that were featured at the 2023 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the director of the Cancer Immunotherapy Center, as well as the associate director of clinical research at the University of Pittsburgh's Hillman Cancer Center.     You can find both of our disclosures in the transcript of this episode, and disclosures of all guests on the ASCO Daily News Podcast are available on our transcripts at asco.org/DNpod.   Jason, there was a lot of exciting data in the immunotherapy space highlighted at the Annual Meeting, and it's great to have you back on the podcast to discuss some of this work.   Dr. Jason Luke: Thanks for having me.    Dr. Diwakar Davar: So, the abstracts that we had selected have several key themes. We'll be covering some of the early advances in melanoma in the stage 2 and stage 2B/C space with KEYNOTE-716. I think this is a study that you know a little bit about seeing you are the presenting author and the principal investigator for the study, as well as the pivotal KEYNOTE-942 trial. And then going on to themes with using third-generation checkpoints, neoadjuvant therapy in non-small-cell lung cancer, and cutaneous squamous cell carcinoma.    But we'll start with KEYNOTE-716. So, this is LBA9505, the study which evaluated pembrolizumab versus placebo as adjuvant therapy in stage 2B and stage 2C melanoma patient population for which historically there was no real effective therapy other than remotely interferon. And these are the final results of the DMFS analysis from this phase 3 trial. So, Jason, what are your thoughts about this, and can you contextualize the results relative to the recent publication?   Dr. Jason Luke: Thanks. I think the important point to level set on this was just a few years ago; this was a population of patients that we didn't treat in clinic. In fact, sometimes they weren't even referred to medical oncology for evaluation. And that was despite the fact that we knew from historical data that the risk of melanoma-specific survival, death from melanoma, was just as high for this population of patients as it was for the patients with stage 3 melanoma, where obviously adjuvant immunotherapy has been a standard for quite some time. And so we launched this clinical trial, KEYNOTE-716. It was a global, randomized phase 3 study of almost 1,000 patients, randomizing patients to either get pembrolizumab or placebo. Importantly, these patients being those with deep primary lesions, stage 2B and 2C with negative sentinel lymph node evaluation.    People will recall that this study hit its primary endpoint on the first protocol-specified analysis at a year. And what we updated at ASCO this year was the final analysis of distant metastasis-free survival. Obviously, an important secondary endpoint because if patients eventually going to develop metastatic disease and pass away, it's the distant metastasis that we worry about. And what we saw in this trial with a landmark 36-month follow-up median of 39 months was that the benefit was increasing. In other words, the magnitude of the hazard ratio change was increasing over time as would be expected, such that at this analysis there was a 41% reduction in the risk of distant metastasis for patients treated with pembrolizumab versus placebo. And we saw a consistent benefit in the recurrence-free survival also out through that same period of time and importantly no change in the safety summary with of course the adverse event profile of pembrolizumab being what it is and well understood across oncology.    So I think these are very important data because they really kind of set the stage for the field. It is now the case that at least discussing adjuvant therapy for patients with stage 2B and 2C is the standard of care; it should be offered to all the patients. Of course, it's always a risk-benefit about whether or not patients want to pursue adjuvant therapy versus consideration of treatment at the time of recurrence. But in my clinic at least, many patients do prefer to try to eliminate the possibility of recurrence and distant metastasis as much as possible.    So I think these are very important...
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    34 mins
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