POPULARITY
Drs. Neeraj Agarwal and Todd Morgan discuss CONTACT-02, KEYNOTE-564, CheckMate-67T, and other notable studies featured at the 2024 ASCO Genitourinary Cancers Symposium, as well as additional key abstracts in prostate, kidney, and bladder cancers that will significantly influence clinical practice. TRANSCRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program and professor of medicine at the Huntsman Cancer Institute at the University of Utah, and editor-in-chief of ASCO Daily News. Today, we'll be discussing practice-changing abstracts and other key advances in GU oncology featured at the 2024 ASCO Genitourinary Cancers Symposium. Joining me for this discussion is Dr. Todd Morgan, the chair of this year's ASCO GU. Dr. Morgan is a urologic surgeon, chief of urologic oncology at Michigan Medicine, and a professor of urology at the University of Michigan. Our full disclosures are available in the transcript of this episode, and the disclosures of all guests on the podcast can be found at asco.org/DNpod. Todd, thank you for joining us today. Dr. Todd Morgan: Thanks so much, Neeraj. It's an honor to be here and I'm just thrilled to be able to do this with you. Dr. Neeraj Agarwal: Thank you. So, the GU meeting showcased significant advancements across the spectrum of GU malignancies. Can you tell us about the hot topics that captured the headlines this year? What did you find exciting this year at the ASCO GU Symposium? Dr. Todd Morgan: The theme of this year's meeting was "20 Years of Advancing Science and Transforming Patient Care," and this reflected ASCO GU's incredible milestone in GU cancer research over the last 2 decades. We were thrilled to welcome over 5,200 attendees from over 70 countries, and, believe it or not, there were more than 875 abstract submissions, compared to more than 300 in the meeting's first year. Most of the participants were present in person and that was fantastic. It enabled great networking opportunities and opportunities for experts, trainees, and mentees to exchange knowledge and ideas. Without a doubt, ASCO GU remains the annual meeting in our field, and it's amazing to hear the breadth and depth of the state-of-the-art science that's presented at this meeting, and so much of it impacts patient care the second that you return home. Additionally, the meeting's focus on diversity and interactivity, networking, multidisciplinary collaboration, and evidence-based care were absolutely phenomenal from my standpoint. We had a lunch session for women's networking that was a huge success—the first time we've done that. The keynote lecture by Dr. Cheryl Lee that talked about ensuring adequate representation in clinical trials was a huge hit, and we had tremendous positive feedback from that lecture. There were also multiple featured sessions on different diagnostic and therapeutic challenges in localized, recurrent, and advanced GU cancers. And, Neeraj, my personal favorite during the symposium is always the Trainee and Early-Career Networking Luncheon on the first day and then the additional networking luncheons on the 2 following days. I had great conversations with a ton of trainees and junior faculty, and I feel so fortunate for the opportunity to get to know the future superstars in our field. So I'd like to kick it back to you for a second because the first day started with a focus on prostate cancer and some of the key clinical trials. A great example is Abstract 17, which was the second oral presentation delivered, and really congratulations to you, Neeraj, on sharing the exciting data from the CONTACT-02 trial which we were eagerly awaiting. And I'd love to get your thoughts on the data that you presented. Could you tell us more about that trial? Dr. Neeraj Agarwal: Yes, Todd, I agree with you. It was such an exciting conference overall, and thank you for your leadership of this conference. So let's talk about the CONTACT-02 trial. It was a phase 3 randomized trial assessing the combination of cabozantinib and atezolizumab versus a second NHT in patients with metastatic castration-resistant prostate cancer after progression on one NHT. This patient population had to have extrapelvic soft tissue metastases, which could be liver metastases, lung metastases, or lymph nodal metastases, and about up to a quarter of patients had liver metastases. And overall, this was a high-risk patient population which was randomized to, as I said, cabozantinib plus atezolizumab versus a second line NHT. And these patients had received a prior NHT, mostly in the mCRPC setting. The co- or dual primary endpoints were overall survival and progression-free survival (PFS). And a unique thing was that PFS was assessed only by RECIST 1.1 because, as per our discussions with regulatory authorities, the trial was focused on soft tissue metastases because of questions in the past that cabozantinib can affect bone lesions in an artifactual fashion, possibly concerns. That's why the PCWG 3 criteria were not used as the primary endpoint, but, of course, indeed used as another key endpoint, so we have information on both. Anyway, coming back to the endpoint 1:1 randomization. The randomization was stratified by presence or absence of liver metastases, prior docetaxel chemotherapy, and the setting in which NHT was given (mCSPC or CRPC). The PFS or primary endpoint was significantly improved with a 35% reduction in risk of progression or death with the cabozantinib-atezolizumab combination versus second NHT. And there was a trend for overall survival, with a hazard ratio of 0.79 favoring the cabozantinib-atezolizumab combination. Interestingly, all subgroups benefitted, regardless of age, region, site of metastases, but we decided to choose three clinical subgroups of interest such as patients with liver metastases, patients with prior docetaxel chemotherapy in the castration-sensitive setting, and bone metastases, and all these subgroups seemed to be benefitting with the strongest signal in the liver metastasis subgroup, with a 57% reduction in risk of progression or death, which I would argue we have never seen with any combination or any regimen in the metastatic prostate cancer setting yet, barring some targeted therapies in very selected patients. But overall, across the non-biomarker-selected patients, we have never seen this kind of signal. Toxicity — no discussion is complete without discussing toxicity, so I would like to highlight that. Safety signal — there were no new safety signals. The most common grade 3-4 adverse events were hypertension in 7%, anemia in 6%, which were similar in both arms, and, of course, diarrhea and fatigue in 4% each. And if we look at the secondary endpoints, such as time to chemotherapy and time to symptomatic skeletal events, they tended to favor the cabozantinib-atezolizumab. To sum it up, cabozantinib-atezolizumab showed a significant PFS benefit, with a 35% reduction in risk of progression or death, with a trend for overall survival in this patient population with an unmet need. So thank you so much, Todd, for allowing me to summarize the results of this trial. Dr. Todd Morgan: Yeah, wow. That's so impressive, and not surprising that you could so fluidly go right through all that data. Amazing. We heard some discussion of the NHT control arm in this trial. Could you discuss that for a bit? Because it obviously has implications on the similar control arm of other ongoing trials in this setting. Dr. Neeraj Agarwal: Absolutely. Pretty much all trials, every trial which has recently been reported or started in metastatic castrate-resistant prostate cancer have a similar second NHT arm. Whether there were multiple immunotherapy trials which we have just reported, or new trials which are starting or just started enrolling patients. And the reason for that is no randomized trial has ever shown superiority of docetaxel chemotherapy over a second NHT after failure of prior NHT in the mCRPC setting. That's number one. If you look at NHT as a control, it is accepted by health authorities globally with multiple recent trials which are just starting also having NHDR and it would not have been possible without the approval of global regulatory authorities across the world. Then, if you look at the recently reported trial in the mCRPC setting with prior treatment with an NHT, there is an indication that chemotherapy may not be superior to NHT. For example, in the KEYNOTE-641 trial in patients with mCRPC with prior NHT, randomizing patients to enzalutamide plus pembrolizumab versus enzalutamide, the median PFS with enzalutamide was 9 months. This is very similar with docetaxel in patients randomized to docetaxel plus pembrolizumab versus docetaxel; the median PFS with docetaxel is 8 months or 8.3 months. And lastly, if you really want to have a comparison of chemotherapy with NHT which has been done after progression on NHT and docetaxel chemotherapy, so later line of mCRPC setting, that is the CARD trial, as you can imagine, cabazitaxel versus NHT, especially in patients with visceral metastasis, which was the point of discussion. For example, people may not feel comfortable randomizing patients to NHT compared to taxane. The hazard ratio for PFS supporting cabazitaxel was 0.79, so almost a 0.80 PFS hazard ratio, which we have never seen turning out to be a clinically significant benefit. So, if you combine all these data together, I think it was absolutely acceptable to us as investigators to have a second NHT as the control arm. And of course, when we are consenting the patient, we have to keep alternatives in mind, and we do talk about those alternatives with the patients. And if alternatives seem more applicable, we should not be talking to patients about those clinical trials or a given clinical trial in the clinic. I'm glad you brought this up, Todd, because this control NHT arm is not an issue with this trial, but all trials which should be presented in GU ASCO in the future meetings in the coming years. So, thank you. Dr. Todd Morgan: Yeah, thank you. It's such an important topic and controversy at some level, but it's a difficult problem to think about and obviously highly relevant to all the trials that we're looking at. Congrats again on that trial, that's tremendous. There was another important randomized phase 3 trial and it covers radiotherapy in patients with high-risk localized prostate cancer. Can you give us your insights on that one? Dr. Neeraj Agarwal: Yeah, Todd, I think you are referring to LBA259, titled "Long-term Results of Dose Escalation of Radiation Therapy from 70 Gy to 80 Gy Combined with Long-term Androgen Deprivation Therapy in High-risk Prostate Cancer: The GETUG-AFU 18 Randomized Trial." As you mentioned, in this randomized phase 3 trial, Dr. Christophe Hennequin and colleagues randomized patients with high-risk prostate cancer, which means they had to have either clinical stage T3 or T4 disease, or PSA ≥20 nanograms per milliliter, or a Gleason score between 8 and 10. These patients were randomized to receive ADT for 3 years combined with either dose-escalated intensity-modulated radiotherapy. So, I'd like to highlight, this was in the context of IMRT in the dose of 80 Gy or a conventional dose of 70 Gy. Now, you can argue that more people are using more than 70 Gy nowadays, but across the world, the conventional dose is still considered 70 Gy. So, 80 Gy versus 70 Gy were tested. Patients also had to have negative lymph node status on CT scans and MRI. The primary endpoint was biochemical progression-free survival or clinical progression-free survival at 5 years following the ASTRO Phoenix definition. Secondary endpoints – and these are quite important secondary endpoints – include overall survival, acute and late toxicity, and quality of life. The best part is that this trial met its primary endpoint with a 44% reduction in risk of biochemical or clinical progression or death in the dose-escalation radiotherapy arm compared with the conventional radiotherapy arm. Interestingly, a significant 52% improvement in prostate cancer-specific survival and a 39% improvement in overall survival was observed in the dose-escalated arm. So, 80 Gy continued to be superior to 70 Gy IMRT across the primary and secondary endpoints. Now, the best part is, regarding the toxicity profile, there was no significant difference between the 2 arms, with 78% of patients in the higher dose arm and 76% of patients in the conventional arm experiencing grade 2 or more toxicities. Dr. Todd Morgan: Great summary and really important, great news for our patients. Of course, it's a slightly different setting as it's high-risk localized prostate cancer. I checked in with our radiation oncologists at the University of Michigan after that [presentation] because I couldn't remember exactly where we are in terms of dose on these patients. And they were like, “Yeah, we've been doing 80 to 90 Gy for several years,” so it's great having this data to support that. And I think, as you said, the field at many centers has already moved that way. And again, the key takeaway from this abstract would be that IMRT, in combination with long-term androgen deprivation therapy, is effective and safe and increases not only the biochemical or clinical PFS rate, but also the cancer-specific survival and overall survival, again, in high-risk localized prostate cancer patients. And it does not appear to increase long-term toxicity. So really important. It'd be great to switch gears and discuss kidney cancer, if that's okay, and talk about some key abstracts in that field. What do you think? Dr. Neeraj Agarwal: There were so many exciting data in all cancers, which is amazing. So, Todd, could tell us about the LBA359, which I thought was one of the most impactful abstract presentations in the ASCO GU this year. It was titled, “Overall Survival Results from the Phase 3 KEYNOTE-564 Study of Adjuvant Pembrolizumab Versus Placebo for Treatment of Clear Cell Renal Cell Carcinoma (ccRCC)." Dr. Todd Morgan: Yeah, this was a really big moment in our field, complete with a mid-presentation round of applause that was well deserved. And so this abstract was presented by Dr. Toni Choueiri from Dana-Farber Cancer Institute, and it included patients with clear cell renal cell carcinoma at intermediate high or high risk of recurrence, meaning that they had positive nodal disease or negative nodal disease with PT 2 and grade 4, or sarcomatoid features, or stage PT 3 or 4. These patients underwent nephrectomy with or without metastasectomy less than 12 weeks before randomization and had not received prior systemic therapy for clear cell RCC. Patients were randomized to receive either pembrolizumab 200 milligrams or placebo IV every three weeks for at least 17 cycles, or until disease recurrence, intolerable toxicity, or withdrawal of consent. Disease-free survival by investigator assessment was the primary endpoint, and overall survival was a key secondary endpoint. In this abstract, Dr. Choueiri and colleagues report results of the third prespecified interim analysis with a median follow-up of around 57 months in 496 patients receiving pembrolizumab and 498 patients receiving placebo. So, just as a reminder to the audience here, the first interim analysis reported at a median follow-up of 24 months and showed a significant reduction of 32% in the risk to recurrence or death in patients in the pembrolizumab arm. Then subsequently in November of 2021, the FDA approved pembrolizumab for the adjuvant treatment of patients with RCC who are at intermediate high or high risk of recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions. At that time, though, overall survival data were still immature. So, at the third prespecified interim analysis with a median follow-up of around 57 months, pembrolizumab showed, for the first time in an adjuvant RCC setting, improved overall survival with a 38% reduction in the risk of death. The estimated OS rate at 48 months was 91.2% with pembrolizumab and 86% with placebo. Furthermore, the OS benefit was observed across key subgroups, including patients with non-metastatic disease, patients with metastatic but no evidence of disease, patients with PDL-1 combined positive score less than or greater than or equal to one, and patients with presence or absence of sarcomatoid features. In each of these subgroups, the forest plot looks really impressive. And the DFS benefit was similar to previously reported interim analyses with a hazard ratio of 0.72. Also, no new safety signals with pembrolizumab were observed so just tremendous data. Dr. Neeraj Agarwal: Thank you, Todd, for such a great summary of these very important results. So the key message from this abstract, as you said, is that after a median follow-up of around 57 months, which is a long follow-up, adjuvant pembrolizumab demonstrates a statistically significant and clinically meaningful improvement in overall survival versus placebo in patients with RCC at high risk of disease recurrence after surgery. And this is, by the way, the first phase 3 study to show improved overall survival with any adjuvant therapy in RCC. Basically, this means we should continue to use adjuvant pembrolizumab or at least bring it up in our discussion with our patients who are in a similar situation with high-risk RCC after surgery. So this is great news overall. Todd, there was another kidney cancer abstract, LBA360, which compared, interestingly, subcutaneous nivolumab with intravenous nivolumab in patients with metastatic renal cell carcinoma. Could you please give us your insight about this abstract? Dr. Todd Morgan: Sure. Really interesting study. Really interesting data that were presented. So as you mentioned, CheckMate 67T was a multicenter, randomized, open-label phase three study led by Dr. Saby George and colleagues that evaluated pharmacokinetics and objective response rate non-inferiority of subcutaneous nivolumab versus IV nivolumab in patients with locally advanced or metastatic clear cell RCC. So patients with measurable disease that progressed during or after 1 to 2 prior systemic regimens and who did not receive a prior immuno-oncology treatment were randomized 1-1 to receive either subcutaneous nivolumab 1200 milligrams every 4 weeks or IV nivolumab 3 milligrams per kilogram every two weeks until disease progression, unacceptable toxicity, withdrawal of consent, completion of two years of treatment, or death. The coprimary pharmacokinetics endpoints for non-inferiority testing were time-average serum concentration over the first 28 days and minimum serum concentration at steady state determined by a population pharmacokinetics analysis. A key secondary endpoint was objective response rate by independent review. So in 248 patients receiving subcutaneous nivolumab and 247 patients receiving IV nivolumab, non-inferiority for the coprimary pharmacokinetics and key-powered secondary objective response rate endpoints were met. The relative risk ratio for objective response rate was 1.33. The median PFS by independent review was 7.23 months in the subcutaneous group and 5.65 months in the IV group. Treatment-related serious adverse events occurred in 6.5% of patients in each group, and study drug toxicity led to 3 deaths in the subcutaneous group and 1 death in the IV group. These results could support using subcutaneous nivolumab as a new option to improve healthcare efficiency, especially since the average injection time with subcutaneous nivolumab was less than 5 minutes. I think we all know what issues are going on in infusion beds across the country, including, I'm sure, your center and mine. Dr. Neeraj Agarwal: Yes, absolutely. I think this is great news for our patients, Todd. Thank you. This shows that we are not only improving therapeutic options and diagnostic tools, but maybe we're also on the right track towards more practical administration routes, assisting in addressing the treatment burden and improving the efficiencies of healthcare systems. We love to have this option available for our patients, especially those who are pressed for time. So, Todd, would you like to move on to bladder cancer now? Dr. Todd Morgan: Yeah, Neeraj, that'll be fantastic. I'm sure listeners would love to hear more about LBA530. Could you tell us more about this one, Neeraj? Dr. Neeraj Agarwal: Of course. I think this abstract is titled "Enfortumab Vedotin in Combination with Pembrolizumab Versus Chemotherapy in Previously Untreated, Locally Advanced or Metastatic Urothelial Carcinoma: Subgroup Analysis Results from EV-302," which was a global phase three study and was presented by Dr. Michiel Van Der Heijden. As our audience may recall, the EV-302 trial was presented at the ESMO 2023 meeting by Dr Tom Powles and the results were very exciting where, for the first time, a combination outperformed traditional gemcitabine-cisplatin chemotherapy. In this trial, patients with previously untreated with metastatic advanced urothelial carcinoma were randomized 1-1 to receive a 3-week cycle of a combination of enfortumab vedotin, which, as we know, is an antibody-drug conjugate targeting nectin-4 expressed on the cancer cells and pembrolizumab, which is a PD-1 inhibitor, versus gemcitabine and cisplatin or carboplatin, which were, until recently, the standard of care in this setting, and continue to be so in many countries in the world. The combination of enfortumab and pembrolizumab reduced the risk of progression or death by 55% and reduced the risk of death by 53% in the overall population. So consistent decrease in the hazard ratios for PFS and OS, and consistent improvement in overall survival and PFS in that previously reported presentation in the ESMO 2023. Now, based on these results, this combination was recently approved by the FDA in December 2023 for patients with advanced or metastatic urothelial carcinoma. So now the abstract, which was presented at the ASCO GU 2024 meeting, reported the results of a prespecified subgroup analysis. Select secondary endpoints included objective responses, duration of response, and safety. In 442 patients receiving the combination of enfortumab vedotin plus pembrolizumab, and a similar number of patients receiving chemotherapy both PFS and OS were higher for the combination of EV and pembro among prespecified subgroups such as race, platinum eligibility, PDL-1 expression, metastatic site, involvement of the liver or kidney function. Interestingly, the combination of EV and pembro reduced the risk of death by 53% in patients with visceral metastasis and 54% in patients with node-only metastasis. The improvement in PFS seems to be consistent regardless of the site of metastasis. In patients with moderate to severe renal function, the risk of death was reduced by 50% in patients receiving combination therapy. This is one of the best findings of these results because we always face challenges in treating patients with suboptimal kidney function and we cannot use cisplatin. Overall, EV plus pembro continues to show superior efficacy compared to platinum-based regimens across subgroups across the subgroups across the site of metastasis regardless of kidney function and so on. Dr. Todd Morgan: Yeah, just amazing data. I love hearing you spell it out like that. So, thank you again for the opportunity for me to sit here with you and listen to you talk about these data. It's impressive that we have been able to expand our therapeutic arsenal for urothelial carcinoma with an immune-targeting regimen that can spare our patients potential side effects of chemotherapy. What would your final takeaway on this abstract be? Dr. Neeraj Agarwal: I agree with you, Todd. I would add that the OS benefit was consistently observed across these select prespecified subgroups, including those historically associated with poor prognosis. The results of this new analysis support the finding of primary results, which indicate that EV plus pembro is a potentially new standard of care for patients with newly diagnosed, locally advanced, or metastatic urothelial carcinoma. Before we wrap up the bladder cancer session and the podcast, Todd, could you please give us insights about LBA531? Dr. Todd Morgan: Yeah, absolutely. I loved getting to hear this abstract presented. This one is titled “Ambassador,” known as the AMBASSADOR trial aligns A031501, a phase 3 randomized adjuvant study of pembrolizumab in muscle-invasive and locally advanced urothelial carcinoma versus observation, that was presented by Dr. Andrea Apolo. It's an open-label, randomized, phase 3 trial that included patients with muscle-invasive urothelial carcinoma of the bladder, upper tract, or urethra. Eligible patients had pathologic tumor stage T2 or greater and/or positive pathologic nodal disease or positive margins at surgery following neoadjuvant chemotherapy, or patients with pathologic tumor stage T3 or greater and/or positive pathologic nodal disease or positive margins at surgery without prior neoadjuvant chemotherapy, and who were cisplatin ineligible or declined adjuvant cisplatin-based therapy. These patients were randomized one to one to either receive pembrolizumab 200 milligrams every 3 weeks for 1 year or observation. The dual primary endpoints were disease-free survival and overall survival. Secondary objectives included evaluation of DFS and OS in PDL-1 positive and negative patients and assessing safety. A total of 354 patients were enrolled to receive pembrolizumab and 348 to the observation arm, and 21% of the patients in the observation arm received a subsequent immune checkpoint inhibitor. At a median follow-up of 22.3 months for DFS, the median disease-free survival in the pembrolizumab arm was 29 months, while it was only 14 months in the observation arm with a hazard ratio of 0.69. At the interim analysis, OS data showed only a trend toward better outcomes in the pembrolizumab arm, which did not, however, reach statistical significance, with a median of 50.9 months in the pembrolizumab arm and 55.8 months in the observation arm with a hazard ratio of 0.98. These results could nevertheless have been impacted by the subsequent treatment of patients in the observation arm with an immune checkpoint inhibitor, especially after the FDA approval of nivolumab in 2021 for patients with muscle-invasive urothelial carcinoma, based on results of the CheckMate 274 trial. In terms of the safety profile, grade three or more adverse events occurred in 48.4% of patients in the pembrolizumab arm and 31.8% of patients in the observation arm. Dr. Neeraj Agarwal: That's great, Todd. This is such a great summary of this trial, and this is exciting news for our patients with muscle-invasive urothelial carcinoma. I'm hoping that pembrolizumab will be another option for our patients when we are discussing adjuvant immunotherapy in the clinic, moving forward very soon. With that, we have covered several abstracts addressing prostate, bladder, and kidney cancer, significantly influencing our medical practices, at least at the current moment or in the near future. Todd, thank you for sharing your insights today. These are undoubtedly exciting updates for all members of the GU oncology community, and we are grateful for your valuable contribution to the discussion. Many thanks. Dr. Todd Morgan: Thanks, for having me, Neeraj; this was really fun. I'm just really proud and excited to still be part of this field, to be part of the GU oncology field, and it continues to be exciting for all the folks who are coming up. Dr. Neeraj Agarwal: Indeed. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you very much. Disclaimer: The purpose of this podcast is to educate and 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. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers: Dr. Neeraj Agarwal @neerajaiims Dr. Todd Morgan @wandering_gu Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas Dr. Todd Morgan: Consulting or Advisory Role: Myriad Genetics, MDxHealth, TerumoBCT Research Funding (Institution): Prostate Cancer Foundation, National Institutes of Health, Department of Defence, GenomeDX Biosciences, Myriad Genetics, MDxHealth
We describes progress in system therapy for advanced papillary RCC. Opportunities and challenges around personalised therapy are discussed
Discussing GU (Genitourinary) Cancer ASCO 2023 Highlights, focusing on practice changing studies with Dr. Toni Choueiri, Director, Lank Center for Genitourinary Oncology and Professor of Medicine at Harvard Medicine School - Dana-Farber Cancer Institute. Covering four important studies: - TALAPRO-2: Ph3 study of talazoparib + enzalutamide vs placebo + enzalutamide as first-line (1L) treatment for mCRPC with homologous recombination repair (HRR) gene alterations - CLEAR: 4-year follow-up of lenvatinib plus pembrolizumab vs sunitinib in pts with advanced renal cell carcinoma - CONTACT-03: efficacy and safety of atezolizumab plus cabozantinib vs cabozantinib alone after progression with prior checkpoint inhibitor in metastatic renal cell carcinoma - THOR: Erdafitinib vs chemo in pts with advanced or metastatic urothelial cancer with select FGFR alteration
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 chemotherapy for muscle-invasive bladder cancer. I think there's always been some discussion around these regimens and how they pair up against one another. Can you tell us about these data? Dr. Jonathan Rosenberg: It's a very interesting study. It was designed back when it was felt that we could not give patients neoadjuvant therapy. And it was designed as either a neoadjuvant or adjuvant approach. Although, in reality, almost everybody who was enrolled in the study got neoadjuvant chemotherapy, which I think speaks to the shift in practice over the last 10 to 15 years towards neoadjuvant rather than adjuvant therapy. It's an interesting trial in that it used a duration of chemotherapy for the MVAC regimen, the dose-dense MVAC regimen that we don't usually use, which is 6 cycles. And functionally, about 40% of patients couldn't make it to 6 cycles and had to stop sooner, versus 4 cycles of q3-week gemcitabine and cisplatin. And what the data show is that the progression-free survival for the entire intent-to-treat population didn't reach significance. But if you looked at the neoadjuvant population only, there was an improvement in progression-free survival as well as overall survival. So, it's sort of a negative positive trial. Negative for the primary endpoint, but positive for key secondary endpoints. They did a very interesting analysis looking at the number of cycles that patients received regardless of arm, but looking at it by arm. And it's clear from that analysis that the more chemotherapy they got, the better they did. Although, the flaw in that analysis is that the healthier patients are, the more chemotherapy they're able to tolerate, and therefore that may translate to an improved overall survival irrespective of the amount of chemotherapy. And this was not necessarily a pre-specified analysis. I think some of the statisticians were clutching their chests during the report of this trial, having talked to several afterward. On the other hand, it does say to me that for a fit, younger patient, it is important to consider dose-dense MVAC instead of gemcitabine and cisplatin. I'll also note, reading the publication from the first part of the trial, that it appears that nobody over 70 was enrolled from everything I could tell. And so, I question the validity of the tolerability of the results for the average 75-year-old that I see in my practice. Although age is not a bright line cut-off for anybody in terms of cancer treatment. But my own experience has been that dose-dense MVAC has been harder to tolerate for a lot of patients in their 70s, whereas I think we should feel quite comfortable giving it to patients in their sixties. And if you ask me how many cycles I would give, I probably wouldn't say 6, for dose-dense MVAC, I would probably say 4. Dr. Rana McKay: Was there a predilection that there was a more aggressive disease like nodal disease or other things to prompt the 6 versus 4? Dr. Jonathan Rosenberg: I think that they stopped primarily for toxicity reasons, but it wasn't clear to me that it was a disease-based issue. And for the neoadjuvant therapy, everyone was supposed to be clinically node-negative on entry, so that probably wouldn't have explained it. Dr. Rana McKay: Very exciting. I know that the data were quite provocative, but I think it's always difficult to interpret these sorts of subgroup of subgroup analyses, and there's a lot of bias in why people may get more versus less. And I think trying to reduce these data to clinical practice is going to be really important, as you've stated. Dr. Jonathan Rosenberg: Rana, I'd also like to talk about some key advances in renal cell carcinoma that were reported at ASCO. Dr. Choueiri presented data on LBA4500, the CONTACT-03 study, which really was the first study of its kind in solid tumors because it addressed a major question in the kidney cancer field and in other fields: Is there a role for immunotherapy rechallenge after progression on immunotherapy? Specifically, the study looked at the efficacy and safety of atezolizumab plus cabozantinib versus cabozantinib alone after progression with prior immune checkpoint inhibitor therapy in metastatic RCC. I'd like you to tell me what you think of this study and the results and how they may affect our practice. Dr. Rana McKay: Absolutely. This was a critically important study looking at the role of IO post-progression on IO. It was a large phase 3 trial that enrolled patients with clear cell and non-clear cell patients. It actually allowed patients with papillary RCC, unclassified RCC, to enroll in the study, whereas most of these studies are excluding patients with non-clear cell disease. Patients had to have progressed on an immune checkpoint inhibitor given either as adjuvant first line or second line, given either as a single agent or in combination with one of the other combos, whether a VEGF or IO. And patients were randomized one-to-one to receive the combination of atezolizumab plus cabozantinib versus cabozantinib alone. And the dosing of the cabozantinib here is at 60 milligrams in the combination, which is the standard dosing of cabozantinib monotherapy. And the primary endpoints for the trial included PFS and OS. And in essence, this trial was a completely negative study. The primary endpoint, which was centrally reviewed, rPFS, was negative. The hazard ratio there was 1.03. Overall survival was also negative with a hazard ratio of 0.94. And when you look at the subgroup analyses, there really wasn't any specific subgroup that seemed to derive any benefit, potentially those that had a prior response to an immune checkpoint inhibitor, but in essence, a negative study. And I think these data are really informative because the discussion at ASCO was conducted by Dr. David Braun, and he actually had conducted a very highly scientific Twitter poll to help guide how to interpret the data and what people do. And from that, about 30% of individuals that completed the poll were actually layering on IO therapy, and continuing IO therapy after somebody progressed on therapy layering in a TKI while keeping the IO backbone going. And I think what this study proves is that we really don't have any really robust data to guide doing that at the present time. And what we may end up doing is compromising the efficacy of the oral TKI or dose-compromising the oral TKI to try to maintain an ineffective IO. And so, I think at the present time these data, while negative, were truly practice-informing. There are other studies that are looking at this strategy as well. I think one of the criticisms here is that atezolizumab really has not had a great track record in renal cell carcinoma in every single context where it was tested, either alone or in combination. It has not met its primary endpoint and it's not utilized as a treatment in RCC. So, there's some discussion that could this be the fact that this is a PDL-1 inhibitor and that it's atezolizumab. And additionally, I think the thing to point out for is that in the modern era if we look at the cabozantinib control arm, cabozantinib in the refractory setting had a PFS of 10.8 months, which is pretty impressive for a later line PFS, if you will. So, there is another study currently ongoing called the TiNivo-2 study that's looking at tivozanib plus nivolumab versus tivozanib alone in a similar patient population. That trial is enrolling only clear cell patients that had progressed on prior IO. So, I think we'll have additional data, but very, I think, informative. I think this question comes up in a lot in other tumor sites as well because of the broad use of checkpoint inhibitors across hematologic and solid tumor malignancies. Dr. Jonathan Rosenberg: I think this was the most informative negative study and the most negative trial I've seen in a while as well. But it did highlight the importance of asking these questions where people assume they know the answer already, and in fact, we often don't, and our assumptions are wrong. So, I thought that was fascinating and very well described. Staying in the kidneys arena. I'd like to talk to you also about the phase 2 KEYNOTE-B61, that's Abstract 4518. It looked at first-line lenvatinib and pembrolizumab across non-clear cell carcinomas. Tell me what you thought of the trial and what your takeaways were. Dr. Rana McKay: This is an important study. I think the treatment of non-clear cell RCC has lagged. I guess the advances have lagged behind clear cell RCC, and really robust phase 3 randomized studies in people with non-clear cell histologies are very limited. This was a single-arm phase 2, so I think we need to kind of take that for what it's worth, that enrolled patients who had non-clear cell RCC per investigator that had received no prior systemic therapy. So, this was a frontline study, and patients received pembrolizumab plus lenvatinib until disease progression or toxicity. The study enrolled a very robust 158 patients, which is pretty impressive for a modern-day non-clear cell cohort. We've seen data from nivo-cabo that had gotten presented previously by Dr. Lee. That study was a single institution, about 40 patients or so if you will. The primary endpoint of this study was objective response rate, and the bulk of the patients that were enrolled were papillary RCC. As you would imagine, around 60% of patients were papillary. It did include around 18% with chromophobe RCC. And when we break things down by IMDC risk category, about 44% of patients were favorable-risk disease. I think the percentage of patients who were favorable is higher than if we were to take an all-comer metastatic RCC patient population. But the objective response rate was pretty impressive at 49% with this combination. The CR rate was right around 5.7%. So, I think certainly a pretty solid signal of efficacy. But again, this is a single-arm phase 2 study. I think what's also really interesting, and I think we have to take subset analyses with a grain of salt if you will, but there were responses that were seen across all histologies. And the prior nivo-cabo study that I had shared with you had previously done a futility analysis for patients with chromophobe RCC, and that cohort actually closed down. And in this study, the response rate for the chromophobe patients, though it wasn't a lot of patients, 29 patients with chromophobia RCC, was around 27.6%, so I think these data are certainly informative. If you look at the waterfall plot, there were some deep responses that were certainly observed, and the bulk of patients had some degree of tumor shrinkage with very little patients that had primary PD. Dr. Jonathan Rosenberg: It's really provocative. So, are we getting to a point where we might start thinking about randomized trials in the non-clear cell population to try to establish the best standard of care? Dr. Rana McKay: Well, I think PAPMET2 is currently enrolling patients. That study is looking at the combination of cabozantinib with atezolizumab versus cabozantinib alone for frontline papillary. PAPMET1, which was led by Dr. Pal, I mean, these studies are really magnanimous because it takes all hands on deck to get these patients enrolled because they're few and far between. So, I definitely think we need to be moving in that direction. And I think we need to be moving away from lumping all non-clear cells into one bucket because I think what we're seeing is that, one, the biology of these tumors is very distinct and unique, and they don't all behave the same to any one given therapy. So, we really need to move away from just lumping all non-clear cells into one bucket and try to actually conduct studies for each specific subtype. Dr. Jonathan Rosenberg: Understood and agree. Let's switch gears for a second and talk about prostate cancer. Can you talk about the data from Abstract 5004, the TALAPRO-2 study of talazoparib and enzalutamide compared to placebo and enzalutamide as a first-line treatment with metastatic CRPC that have HR homologous recombination repair gene alterations? Dr. Rana McKay: Absolutely. So the TALAPRO-2 study is one of three studies that have looked at the combination of PARP inhibitors with an ARSI in the frontline mCRPC setting. And this trial randomized patients to talazoparib and enzalutamide versus placebo enzalutamide. And again, this was first-line mCRPC. Patients were allowed to have received prior docetaxel or prior abiraterone in the castration-sensitive setting, and the primary endpoint was overall survival. At GU ASCO this year, we saw the top-line data from TALAPRO-2 first get presented. And what was actually presented at this meeting was the subset of patients that were HRR-mutated only. They had two cohorts: an all-comer cohort that was previously presented, and then now they're presenting the subset of the patients that were HRR-mutated. And I think what we've seen across the board is that the efficacy of PARP inhibitors kind of differs by underlying HRR mutations. When we look at the entire population of HRR-deficient patients, the study was positive, talazoparib plus enzalutamide resulted in an improvement in rPFS compared to enzalutamide placebo. The hazard ratio there was 0.45. And then when we break things down by selected gene groups, they did this subset analysis in patients with only BRCA1, only BRCA2, only PALB2, only CDK12, ATM CHEK2 if you will. The data are most robust for those patients with a BRCA1/2 alteration with hazard ratios of 0.17, 0.19. Again, this is for rPFS. But then, when we look at some of these other mutations, like ATM CHEK2, hazard ratios are higher, 0.76, 0.90. So, the effect size really kind of drops off for those non-BRCA1/2 altered HRR genes. But if we look across the different subgroup analyses, the interim OS data for the HR deficient, the time to PSA, time to cytotoxic chemo, all of that favored the combination versus placebo enzalutamide for patients that were HR deficient if we just lumped everybody all together. Dr. Jonathan Rosenberg: How does this fit into the general landscape around this question with selection versus not selecting for HRR alterations? Dr. Rana McKay: The data that were presented were for the selected patients, and I think that that's not where the controversy is. I think that the selected patients are the ones that seem to derive the most benefit. It's interesting because in looking at the data from PROpel and the final FDA label based off of the PROpel data, the label is only for BRCA1 and 2 patients and not for all comer HRR. It's even a more restricted label than olaporib monotherapy. So, I think it's going to be interesting. I don't know what the right answer is. I think it's going to be interesting to see how this is going to unfold for TALAPRO-2 and even for MAGNITUDE, if you will, like, how select is the selected population going to be. But at the present time, I think the label is what it is for olaparib plus abiraterone in those BRCA1/2 frontline. My hope is that this population is shrinking because everybody should be getting escalated in the metastatic hormone-sensitive setting, and we shouldn't be having people who are naive to an ARSI in frontline mCRPC. Dr. Jonathan Rosenberg: Understood and agreed. Dr. Rana Mckay: Well, thank you so much, Jonathan, for joining me today. It's really been a pleasure kind of going through all of the compelling advances in GU cancers from ASCO. I think it was a really exciting meeting, and thanks for your time. Dr. Jonathan Rosenberg: My pleasure. It's been great to talk to you today. Dr. Rana Mckay: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcast. Disclaimer: 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. Guests' statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers: Dr. Rana McKay @DrRanaMcKay Jonathan Rosenberg @DrRosenbergMSK Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Rana McKay: Consulting or Advisory Role: Janssen, Novartis, Tempus, Exelxis, Pfizer, Bristol-Myers Squibb, Astellas Medivation, Dendreon, Bayer, Sanofi, Merck, Vividion, Calithera, AstraZeneca, Myovant, Caris Life Sciences, Sorrento Therapeutics, AVEO, Seattle Genetics, Telix, Eli Lilly, Pfizer, Bayer, Tempus Dr. Jonathan Rosenberg: Honoraria: UpToDate, Medscape, Peerview, Research To Practice, Clinical Care Options, Physician Education Resource, MJH Life Sciences, EMD Serono, Pfizer Consulting or Advisory Role: Lilly, Merck, Roche/Genentech, AstraZeneca/MedImmune, Bristol-Myers Squibb, Bayer, BioClin Therapeutics, QED Therapeutics, Pharmacyclics, GlaxoSmithKline, Janssen Oncology, Astellas Pharma, Boehringer Ingelheim, Pfizer/EMD Serono, Merck Therapeutics, Immunomedics, Tyra Biosciences, Infinity Pharmaceuticals, Gilead Sciences, Hengrui Pharmamedical, Alligator BioScience, Imvax Research Funding (Institution): Genentech/Roche, Seattle Genetics, Bayer, AstraZeneca, QED Therapeutics, Astellas Pharma Patents, Royalties, Other Intellectual Property (Institution): Predictor of platinum sensitivity
Toni Choueiri, M.D., is the Director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute (DFCI). He is the Co-leader of the Kidney Cancer Program and the Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School. He has received the George Canellos Award for Excellence in Clinical Investigation and Patient Care, the Eugene Schonfeld Award from the Kidney Cancer Association, and last year he was inducted into the prestigious Giants of Cancer Care. He has over 675 PubMed indexed publications and is the lead investigator of multiple, national, and international phase I-III trials in GU cancers. “A great physician is not measured by the number of publications or how fast you become a professor or the awards you have received. A great physician is measured by people saying (not in your presence) - ‘I want to send my mom to this person.' That to me is a great physician.” Tune into another conversation on The Medicine Mentors as we talk about rediscovering ourselves, building trust, and aiming for peak performance in medicine with Dr. Toni Choueiri. Pearls of Wisdom: 1. There is no one path to success; the path differs for everyone, and so rather than having a tunnel vision, we should be honest with ourselves and keep our mind open to all possibilities so that we can really find what makes our heart palpate. 2. We are all going to face scenarios where a patient needs our help and at the same time we have a call from our family or a meeting for our research project, or an issue in the lab. The question is what comes first, and categorically the patient should always come first and should be the priority. 3. We should ask ourselves: ‘Am I a doctor that my physician friends would send their mom or a loved one to?' And its really when we start to continually raise the bar for our personal performance that we move to the next level.
Featuring perspectives from Prof Laurence Albiges, Dr Toni Choueiri and Prof Thomas Powles, moderated by Dr Brian Rini, including the following topics: • Available Data with and Ongoing Investigation of Immune Checkpoint Inhibitors for Nonmetastatic Renal Cell Carcinoma (RCC) — Prof Powles o Introduction (0:00) o Case: A woman in her early 60s after left nephrectomy (T3aN0M0 clear cell carcinoma) — Swati Vishwanathan, MD (1:39) o Cases: A man in his early 50s develops renal dysfunction after 2 cycles of adjuvant pembrolizumab for RCC and a man in his late 60s with Stage III clear cell RCC (ccRCC) discontinues adjuvant pembrolizumab due to severe musculoskeletal pain and joint swelling — Justin Peter Favaro, MD, PhD and Priya Rudolph, MD, PhD (6:05) o Faculty presentation: Prof Powles (11:03) • Evidence-Based Selection of First-Line Therapy for Metastatic RCC — Dr Choueiri o Case: A man in his early 70s with metastatic RCC enrolls on the PDIGREE trial and receives nivolumab/ipilimumab without response followed by cabozantinib — Helen H Moon, MD (21:32) o Cases: A man in his early 70s receives ipilimumab/nivolumab for widely metastatic RCC and develops autoimmune hepatitis and a man in his early 60s with metastatic ccRCC receives ipilimumab/nivolumab followed by nivolumab with response but develops hypothyroidism and hypoadrenalism — Victoria Giffi, MD and Philip L Brooks, MD (25:33) o Faculty presentation: Dr Choueiri (36:38) • Treatment Options for Relapsed/Refractory RCC — Dr Rini o Case: A woman in her early 60s with metastatic ccRCC receives lenvatinib/pembrolizumab but develops difficult-to-manage hypertension — Eric H Lee, MD, PhD (46:04) o Case: A woman in her mid 60s with metastatic ccRCC and somatic VHL gene mutation receives ipilimumab/nivolumab and develops a solitary brain metastasis — Sunil Gandhi, MD (52:36) o Faculty presentation: Dr Rini (57:54) • Management of RCC Among Special Patient Populations — Prof Albiges o Case: A man in his late 60s with Waldenström macroglobulinemia and metastatic papillary RCC receives first-line ipilimumab/nivolumab followed by nivolumab but develops disease progression, including brain metastases — Nikesh Jasani, MD (1:07:58) o Case: A woman in her early 70s with a history of psoriatic arthritis develops metastatic ccRCC, receives pembrolizumab/axitinib and develops elevated liver function tests — Georges Azzi, MD (1:12:38) o Faculty presentation: Prof Albiges (1:18:45) CME information and select publications
Investigators are only as productive and strong as the members of their team. That is only one of many nuggets of wisdom from Dr. Toni K. Choueiri in this lively ACCRU podcast episode. Dr. Choueiri is the Director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute (DFCI), co-leader of the Kidney Cancer Program at Dana-Farber/Harvard Cancer Center, and the Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School. He is also a member of the ACCRU Board of Directors. Dr. Choueiri also discusses the success of the phase 3 METEOR trial and what excites him about the progress in GU oncology. His insights on the work itself of an investigator are invaluable: the importance of facing the truth that success is not serendipity but the result of hard work and knowledge over time.
Pour retrouver l'épisode : https://www.podcastics.com/episode/216697/link/ Soutenez-nous !
Dans cet épisode nous revenons sur le livre "L'emprise au travail" de Wadih Choueiri. Une interview que je vous recommande chaudement tant elle fait du bien à écouter. Bonne écoute Soutenez-nous !
Dr Toni Choueiri from Dana-Farber Cancer Institute in Boston, Massachusetts, discusses recent therapeutic advances in the care of patients with renal cell carcinoma. CME information and select publications here (http://www.researchtopractice.com/OncologyTodayRCC22).
Discussing practice-changing Genitourinary (GU) Cancer studies presented at the European Society of Medical Oncology 2022 with Dr. Toni Choueiri, Chief - Director, Lank Center for Genitourinary Oncology and Professor of Medicine at Harvard Medicine School - Dana-Farber Cancer Institute.
Bob Figlin, MD, and Toni Choueiri, MD, the director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, discuss the early results from the COSMIC-313 trial, which Dr. Choueiri presented at ESMO 2022. The trial enrolled previously untreated patients with metastatic clear cell renal cell cancer who were classified as intermediate- to poor-risk. Standard of care doublet therapy, nivolumab (nivo) plus ipilimumab (ipi), was compared with triplet therapy, consisting of nivo-ipi plus cabozantinib. Triplet therapy improved progression-free survival compared with doublet therapy, specifically in the intermediate-risk group. Dr. Choueiri also discussed the complicated landscape in RCC and how practicing oncologists can evaluate patients for appropriate treatments as well as how to communicate effectively with patients about the factors that contribute to that decision.
Nick Pannoni , 62, renal cell carcinoma (kidney cancer), Forestdale, with Dr. Toni Choueiri, Director of the Lank Center for Genitourinary Oncology, Dana-Farber
Nick Pannoni, 62, renal cell carcinoma (kidney cancer), Forestdale, with Dr. ToniChoueiri, Director of the Lank Center for Genitourinary Oncology, Dana-Farber● Six years ago, Nick, a father of four, was diagnosed with prostate cancer, but it wascaught early enough where doctors only needed to remove his prostate for him to bedeclared cancer-free.● Unfortunately, three years later, cancer had returned, but this time it was acompletely different type of cancer: kidney cancer. Specifically known as renal cellcarcinoma, Nick's left kidney was removed as it had been encased in the cancer.● Once Nick recovered, his oncologist Dr. Steven Chang mentioned that he may wantto see Dr. Toni Choueiri, the lead author of the KEYTRUDA study.● Nick entered the clinical trial as a double-blind participant, meaning he would notknow if he received the medication or a placebo. Though there isn't a way to know for sure, Nick believes he received the drug as he experienced several of thecommon side effects.● Once high-risk, there is now no evidence of disease. Nick continues to move forwardand live his everyday life. He gets blood work and scans every four months, but onlyto make sure that cancer has not come back. Kidney cancer facts● Kidney cancer is a type of cancer that starts in the kidney. Cancer starts when cells inthe body begin to grow out of control.● About 79,000 new cases of kidney cancer (50,290 in men and 28,710 in women) willbe diagnosed in 2022.● Kidney cancer is about twice as common in men than in women.● Most people with kidney cancer are older. The average age of people when they arediagnosed is 64 with most people being diagnosed between ages 65 and 74. Kidneycancer is very uncommon in people younger than age 45. Dr. Toni Choueiri● Dr. Toni Choueiri is the Director of our Genitourinary (GU) Oncology Disease Centerand the Lank Center for Genitourinary Oncology.● Dr. Choueiri can speak about the challenges of treating kidney cancers and theimportance of clinical trials.● He is the lead investigator of multiple national and international phase one, two andthree trials in GU cancers.● Dr. Choueiri is interested in developing novel therapies (including immunotherapies)and biomarkers in GU malignancies, including kidney cancer. His research alsofocuses on epidemiology, diagnosis and treatment outcomes of GU cancers usinglarge scale approaches such as meta-analyses from available published trials ornational databases.
Anne Gross, PHD, RN, Senior Vice President and Chief Nursing Officer, Dana-Farber● Anne Gross, PhD, RN is senior vice president for patient care services and chiefnursing officer. There are more than 700 registered nurses, nurse practitioners,clinical specialists, and nurse scientists working at Dana-Farber.● Anne can give insight into the challenges overcome by the amazing nursing staffduring the COVID pandemic. What they have done and achieved since 2020 inspiresher and keeps her optimistic for the future.● She can also provide insight about the often emotionally powerful relationshipnurses form with patients and why it's a unique nursing career.● Since 2020, along with continuing to provide cancer treatment, oncology nurses hadthe added challenge of protecting patients and each other from COVID hrough strictisolation procedures and the use of personal protective equipment (also known asPPE).● The nurse acquired new skills to care for immunocompromised patients in specialCOVID intensive care units.● In other settings, oncology nurse navigators transitioned their practice to be remoteso they could care for patients while they were in their homes through telehealthvisits and clinical trial nurses innovated standard operations, such as shippinginvestigational drugs to patients' homes, to enable them to safely remain on theirstudies.● Anne takes great pride in Dana-Farber's nursing and patient care services staff andthe patient experience at Dana-Farber remains as strong as ever: As a patient youare never alone.● Anne leads a nursing staff focused on the future:○ Continuing to manage through the lingering threats of the pandemic whilefocusing on building a pipeline for the future○ Addressing the national nursing shortage with the goal of training the nextgeneration of oncology nurses ○ Expanding access to our care by opening Foxborough location and expandingSouth Shore Nick Pannoni (PAH-NO-NEE), 62, renal cell carcinoma (kidney cancer), Forestdale, with Dr. ToniChoueiri (SHWERRY), Director of the Lank Center for Genitourinary Oncology, Dana-Farber● Six years ago, Nick, a father of four, was diagnosed with prostate cancer, but it wascaught early enough where doctors only needed to remove his prostate for him to bedeclared cancer-free.● Unfortunately, three years later, cancer had returned, but this time it was acompletely different type of cancer: kidney cancer. Specifically known as renal cellcarcinoma, Nick's left kidney was removed as it had been encased in the cancer.● Once Nick recovered, his oncologist Dr. Steven Chang mentioned that he may wantto see Dr. Toni Choueiri, the lead author of the KEYTRUDA study.● Nick entered the clinical trial as a double-blind participant, meaning he would notknow if he received the medication or a placebo. Though there isn't a way to know for sure, Nick believes he received the drug as he experienced several of thecommon side effects.● Once high-risk, there is now no evidence of disease. Nick continues to move forwardand live his everyday life. He gets blood work and scans every four months, but onlyto make sure that cancer has not come back.
In this episode, we are joined by Dr. Michel Choueiri, CEO at CovidCheckToday, an at-home COVID testing company using Rapid Antigen COVID-19 Test, which targets proteins that are expressed on the virus, The RT-PCR Test, which is the Gold Standard in PCR testing and Video Monitoring that monitors your COVID-19 test virtually and send you a report with your results. Covid Check Today is currently servicing the Greater San Diego Area, Los Angeles, Orange County California, Denver Colorado, Las Vegas Nevada, and Miami Florida. Tune in to learn more!
Guest host, Dr. Neeraj Agarwal, ASCO Daily News editor-in-chief and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, discusses the practice-changing KEYNOTE-564 and SWOG 1500 trials with Drs. Toni Choueiri and Sumanta "Monty" Pal. Dr. Choueiri is director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute and Dr. Pal is co-director of City of Hope's Kidney Cancer Program and associate editor of Cancer.Net. (This episode was recorded on 11/18/2021) Transcript Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News podcast. I am Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program, and the professor of Medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I'm delighted to welcome two internationally recognized leaders in the field, Dr. Toni Choueiri and Dr. Sumanta (Monty) Pal, for a discussion about two practice-changing studies in kidney cancer published this year-- KEYNOTE-564 and SWOG 1500. As a quick introduction, Dr. Choueiri is the director of Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute. He's also the Jerome and Nancy Kohlberg Chair, and professor of medicine at the Harvard Medical School. Dr. Sumanta "Monty" Pal is a professor in oncology, and co-director of City of Hope's Kidney Cancer Program, and he is an associate editor of cancer.net of ASCO. Our full disclosures are available in the show notes. And disclosures relating to all episodes of podcasts can be found on our transcripts at ASCO.org/podcast. Toni and Monty, what a day it has been for our patients with kidney cancer. I woke up with the news of the U.S. Food and Drug Administration (FDA) approval of the first ever adjuvant immunotherapy for patients with renal cell carcinoma. It is so great to have you both on the podcast today. Dr. Monty Pal: Glad to be here. Thanks, Neeraj. Dr. Toni Choueiri: Thank you, Neeraj. So glad to be here. Dr. Neeraj Agarwal: So, let me start by asking questions to you first, Toni. So, you recently published the primary results of the phase 3 KEYNOTE-564 study, showing the efficacy of adjuvant therapy with pembrolizumab and immune checkpoint inhibitor in patients with renal cell carcinoma. And this study led to the approval of pembrolizumab this morning. So, please tell us more about the study design and why did you do this study. Dr. Toni Choueiri: Thank you, Neeraj. And thank you, really, ASCO for this wonderful podcast series. And a big hit, I always listen to them when I'm driving or jogging. And really, thanks for this opportunity because kidney cancer adjuvant therapy has been something like a holy grail we're trying to find for a long, long time. The first adjuvant trial, a randomized trial, in renal cell cancer was in 1973 with radiation therapy. And since that time, all the trials except for one have been a complete failure in a way. And the first adjuvant immunotherapy trial was with old immunotherapy cytokine that we don't use much anymore and was in 1992. I was not done with medical school. I was not actually done with high school at that time, let alone medical school. And now that we have, as we all know, a revolution in the oncology field through these immune checkpoint inhibitors that reinvented immunotherapy in cancer, and now that pembrolizumab has shown activity in patients with more advanced disease, we thought about taking this into the adjuvant setting, a setting of patients where they were subjected to surgery. But on the pathology report, we knew that their risk of this cancer coming back, of recurrence, is somewhat intermediate high or high. These are patients that have stage 2 but grade 4, stage 3, D3, D4. These are patients that had node-positive resected. And we took even patients where the kidney is out, but, also, they had a removal of a metastatic site--let's say a lung metastasis--within a year of removing the kidney. And we know these patients we refer to as M1NED are at quite high risk of recurrence. And we randomly assigned 994 patients to receive pembrolizumab for a year versus placebo. And after a median follow-up of only 2 years--so I want to insist here that this is short for any trial in general--we saw a decrease in the risk of recurrence or death. The hazard ratio for disease-free survival was 0.68. So, a 32% decrease in the risk of recurrence or death. We looked at safety, and we already are familiar in the field of GU oncology with pembrolizumab. And we didn't see when we looked at the safety profile any surprises, any enhanced toxicity. Of course, immune-related adverse events are the number one concern with pembrolizumab. There were no deaths on trial related to pembrolizumab. We saw around 7% of patients needing high dose steroid to medicate these immune-related adverse event, and some patients had to come off therapy for that. We also took a look, Neeraj, an early look, at overall survival. We only had 25% of events, 51 deaths. And we did not meet the very rigorous statistical significance that is needed to say that study is positive for overall survival. But the hazard ratio was 0.54, a 46% decrease in the risk of death, which is kind of encouraging. And after a year, the curve starts to separate. Before a year, they're not separating. And that is consistent with prior studies in general. Dr. Neeraj Agarwal: This is a very interesting point you just raised, that DFS, disease-free survival, is strongly positive. And even overall survival is trending in the right direction, right? Dr. Toni Choueiri: Correct. Dr. Neeraj Agarwal: That's great. So obviously, I would like to raise another point here. When we talk about adjuvant study, we usually think about a localized kidney cancer, which is removed by the surgeon, and then [the] patient is coming to see us for treatment in adjuvant setting. But this study, I would like to highlight, as you said, also included patients who had oligometastatic disease, had successful surgical removal of the oligometastatic disease, and they were also eligible for this trial. Dr. Toni Choueiri: Yes, absolutely. And I think this is somewhat on the recent side in clinical trials in kidney cancer. The reason for that is that, in practice, we see those patients. And we even had two small trials in the TKI era with sorafenib and pazopanib, small studies, were also completely negative. So, we thought here that we should not exclude these patients. They end up being 6%, 7% of all participants, but this remains an area of unmet medical need. Dr. Neeraj Agarwal: So, how is the hazard ratio in those patients who had metastatic disease removed and then treated with pembrolizumab? Dr. Toni Choueiri: Yeah, it was very low. It was 0.2, so 0.29. And this was great to see. I don't want to go into really over-interpreting these results. All the hazard ratio--when you look at subgroup analysis or in the forest plot, all the hazard ratio are less than 1. We didn't see something--let's say 1.5--in favor of pembrolizumab. Now you go into a smaller subgroup, then your confidence intervals are very large and hard to interpret, except that to say, look, on average there could be a significant benefit here, but we can't tell. Dr. Neeraj Agarwal: Sure, absolutely. I agree with you. So, how this is going to affect the current treatment paradigm, which is for patients with newly diagnosed metastatic RCC, where combination of VEGF-TKI plus immunotherapies (IOs) or IO/IO combinations have become standard of care or treatment paradigm? Dr. Toni Choueiri: I do believe it will be a standard of care currently in the right population. There are a lot of unanswered questions, but that will be answered hopefully with more follow up. We have already, beside these results, reported--so these results were reported in the plenary session at the 2021 ASCO [Annual Meeting]. But later on, another analysis dealing with patient-reported outcome and quality of life was reported at ESMO and also showed no detriment in quality of life--that's the voice of the patient--no detriment with pembrolizumab (pembro). There is a lot still to do and a lot of unanswered questions, such as the non-clear cell histology, those patients who had surgery of their metastatic disease more than a year. But most important, I think, two questions. One, how can you know from the get-go who are the patients that need adjuvant pembrolizumab? We do not have any valid ctDNA. And I know Dr. Pal was involved with a lot of these type of research. We don't have any ctDNA test that is really that faithful and sensitive in the MRD space in renal cell. Many of us are working, so we don't know. We may end up over-treating patients that need surgery only. And actually, we may end up under-treating patients that need, perhaps, pembro, and another drug. And the second thing in those patients--and I hope it does not happen, but unfortunately, it will to some extent--whose tumor progress on adjuvant pembrolizumab, what do you do? What's the treatment paradigm? And actually, there is no data. This is a data-free zone. And I would think somebody whose tumor progressed, tumor continued to grow or grows, while they're actively on pembrolizumab, on IO, is way different than someone whose tumor comes back after 2 or 3 years from stopping the drug. Should we treat them with the same drug? Should we treat them with the TKI plus IO? Luckily, there are trials that are ongoing in patients whose tumor progressed after PD-1/PD-L1 inhibitor to give them a TKI as a control arm, or a TKI plus an immune checkpoint inhibitor. And I know Dr. Pal is very heavily involved with such trials. So, hopefully, we will answer this question, but not anytime soon. Dr. Neeraj Agarwal: Very interesting, and definitely new results are posing new challenges in how we practice medicine here in the coming future. So, Monty, you are leading a trial with a very similar trial with atezolizumab. And I'm really hoping, we are all really hoping, that we see the other trial being positive, so we have more treatment options for our patients. Dr. Monty Pal: I couldn't agree with you more. I mean, I definitely think that Toni's study really adds a lot of fuel to the fire suggesting that this strategy of adjuvant immunotherapy may be successful in localized renal cell. Dr. Neeraj Agarwal: And I'm not going to really delve into the side effects of pembrolizumab and atezolizumab because these drugs are used quite often. They are in widespread use for different types of cancer. But just a quick question, any safety signal, Toni? Did you see any safety signal with pembrolizumab in this patient population? Dr. Toni Choueiri: Yeah, this is an excellent question. So, nothing that would be different than using pembrolizumab overall knowing in other diseases as a single agent. So, this drug not first in human, as you know, and it's been approved in combination or as a single agent in many diseases. A tumor that the three of us treat is bladder cancer, and we know from another study how to use pembrolizumab. I think that the use of corticosteroid is somewhat of an objective way, at least to me, in looking at immune-related adverse event. And it has been between 5% to 10%, so we're not way off here. But there is no doubt that there are patients that we had no death on trial attributed to drug that may have, with pembrolizumab, some serious toxicities. We had patients that had autoimmune diabetes, hypophysitis, pneumonitis--quite uncommon, but not impossible. Dr. Neeraj Agarwal: We'll still need to keep an eye for that, basically. Dr. Toni Choueiri: No doubt. Dr. Neeraj Agarwal: Yes. So, changing gears, let's talk to you, Monty. You recently presented the primary results of the SWOG 1500 trial in patients with metastatic non-clear cell renal cell carcinoma. Could you please tell us why you did this study and how this study's design was unique compared to similar studies in this setting? Dr. Monty Pal: Yeah. No, absolutely. Toni did a great job of outlining areas that are sort of free of data in the adjuvant space, particularly with immunotherapy. I think that data-free area for us in kidney cancer for a long time has been non-clear cell histology. We just don't really know how to treat them. And I actually got advice from Toni when I was devising SWOG 1500. We planned it out as a very simple study comparing sunitinib and cabozantinib. And Toni will remember this history well. It sort of went through several iterations. The study blossomed into a six-arm trial. Ultimately, it turned into a four-arm study, looking at sunitinib versus cabozantinib versus two other MET inhibitors--savolitinib and crizotinib. And ultimately, the study was boiled down to essentially what we'd originally proposed. Two of the MET inhibitors--savolitinib and crizotinib--failed to surpass that initial analysis for PFS. So, ultimately, we demonstrated a superiority with cabozantinib over sunitinib for progression-free survival. Dr. Neeraj Agarwal: So, what is the current treatment paradigm for patients who have newly diagnosed metastatic papillary RCC now? Dr. Monty Pal: I think for patients who don't have genomic selection, I think that cabozantinib remains the standard. I really want to champion- and maybe Toni can talk a little bit more about this--a study that Toni is leading called the SAMETA trial, which I think has a really innovative design. And it's going to be genomically characterizing patients and randomizing to savolitinib with durvalumab or sunitinib. Tell me, Toni, if I have the design right there. Dr. Toni Choueiri: Yes. Actually, this is a specific study in a specific population. It's not in papillary RCC as much as in those 30%, 40% of papillary RCC that have MET-driven tumors, so MET alteration, whether through chromosome 7 duplication, through chromosome 7 trisomy, through mutation or amplification. These patients will get either control arm or they will get savolitinib, which is a pure MET inhibitor that is devoid of VEGF-related toxicities, savolitinib plus durvalumab, or durvalumab alone. So, two experimental arms and one control. And the reason for this is we saw activity and quite a good toxicity profile with savolitinib, a pure MET inhibitor, over sunitinib in an earlier trial that was sunitinib against savolitinib in selected patient populations. The study had to close early. So, despite the numerical difference, this was not statistically significant. And then in another study led by Dr. Powles and colleagues, there was also some interesting activity how durvalumab could augment that activity. So, we're launching a phase 3 trial with three arms that you described very well. Dr. Neeraj Agarwal: That's wonderful. So, what are the next steps, Monty? I mean, this is amazing to see you designing an investigator-initiated trial. This was your concept. You designed it. You built this to be a huge multicenter trial, which was open across the country, funded by the National Cancer Institute. And congratulations for making that happen. It's rare for us to see these trials going from a concept stage to a national trial, and then changing the standard of care. So, what are the next steps now for you and your team in SWOG for papillary RCC or metastatic papillary RCC? How do you build out further with the backbone of cabozantinib? Dr. Monty Pal: I really appreciate the question, Neeraj. It's so critical to understand that we're just not quite done yet. Toni's study, as I've mentioned, is incredibly innovative. I'm also really thrilled to be working with someone who you've mentored so well, Ben Maughan, at the Huntsman Cancer Institute in Utah. And he's actually designed a brilliant study, which we're going to be leading together, which looks at cabozantinib with or without atezolizumab. Recently, in a study that you and I and Toni were a part of that we just published in JCO, we actually saw quite impressive response rates with the combination of cabozantinib and atezolizumab in patients with papillary RCC, around 47%. Those response rates were actually replicated in a separate study run by Joe Lee at Memorial Sloan Kettering. In the context of papillary disease response rates were again above a threshold of around 40%. So, I think there's something to it. But until we really subject this to randomization, I think we're not going to know whether or not cabo plus IO is standard. So, I encourage everyone to consider Toni's study. I encourage everyone to look out for our trial of cabo plus or minus atezo, which should be rolling out next year. Dr. Neeraj Agarwal: What is the name of the trial, or the number, for our audience? Dr. Monty Pal: Yeah, we lucked out with another great number. We got 1500 for the first trial. This is going to be SWOG 2200. So SWOG 2200, and I think it's due to open maybe in the first quarter of 2022. Dr. Neeraj Agarwal: That's fantastic news. Any new signal? We know cabozantinib is already approved for our patients with metastatic RCC, courtesy METEOR trial led by Dr. Choueiri. Toni, it's amazing to see how many times you have changed standard of care for our patients with metastatic RCC. So, any new safety signal of cabozantinib in this patient population with metastatic papillary RCC? Dr. Monty Pal: Nothing that appreciated. The toxicity profile was pretty much on par with what you'd anticipate for cabozantinib in the setting. Major side effects were hypertension, hand-foot syndrome, [and] diarrhea. Nothing that really sort of stood out relative to what we would expect in a clear cell population of patients. Dr. Neeraj Agarwal: That's great. Any final messages for our patients, for our audience, for our listeners? Dr. Toni Choueiri: Well, let me start, and maybe Monty can add. It's been, and it hopefully will continue to be, this humbling experience, where median survival from metastatic RCC in mid-2000--not long time ago during our training--has been 1 year. And now in metastatic disease, it's 4 to 5 years. And that is only going to get better. And then it's even more humbling to be in a time where you can talk about adjuvant treatment in this disease, renal cell cancer, that continues every year to kill, unfortunately, 14,000 Americans. That's just in the U.S. alone. So, we have to continue in getting more targets, more drugs, more reasonable combination, and the right patient, whether through specific biomarker that are tissue or blood-based or specific liquid biopsies that can tell you who has and who doesn't have cancer at the microscopic levels. Dr. Neeraj Agarwal: Thank you. How about you, Monty? Any final message for our audience? Dr. Monty Pal: I couldn't have summarized it better than Toni, just such a wonderful statement around optimism for what we've achieved so far and what's yet to come. And if I could emphasize to anyone in the audience today the need to keep progressing the field further with clinical trials, I think that would be my underlying message. Dr. Neeraj Agarwal: Thank you again, Toni, Monty, for your valuable insights and thoughts. Thank you for all the inspiration. This is indeed so inspiring to see your work, which is changing the lives of our patients on a daily basis. Our listeners will find links to your studies in the transcript of this episode. I wish you all the best. Dr. Toni Choueiri: Thank you. Dr. Neeraj Agarwal: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you so much. Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Pfizer, Merck , Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Foundation Medicine, Gilead Sciences Research Funding (inst.): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas Dr. Sumanta (Monty) Pal: Consulting or Advisory Role: F. Hoffmann LaRoche, F. Hoffman Research Funding (inst.): Eisai, Genentech, Roche, Exelixis, Pfizer Travel, Accommodations, Expenses: Genentech, Seattle Genetics Dr. Toni Choueiri: Employment: Dana Farber Cancer Hospital Leadership: Dana Farber Cancer Hospital, NCCN, KidneyCan, ASCO, ESMO Stock and Other Ownership Interests: Pionyr, TEMPEST Honoraria: NCCN, UpToDate, Michael J. Hennessy Associates, ASCO, Harborside Press, Analysis Group, AstraZeneca, Alexion Pharmaceuticals, Sanofi/Aventis, Bayer, Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Merck , Novartis, Peloton Therapeutics , Pfizer, Corvus Pharmaceuticals, Ipsen, Foundation Medicine, Eisai, PlatformQ Health, Clinical Care Options, Navinata Healthcare, Kidney Cancer Journal, Exelixis, Prometheus, Lpath, NEJM, Lancet Oncology, Cerulean Pharma, alligent, EMD Serono, HERON, Lilly, Janssen Oncology, IQvia, Aveo, and NCI. Consulting or Advisory Role: Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, Bristol-Myers Squibb, Roche/Genentech, Eisai, Foundation Medicine, Cerulean Pharma, AstraZeneca, Exelixis, Prometheus Laboratories, alligent, Ipsen, Corvus Pharmaceuticals, Lpath, Alexion Pharmaceuticals, Sanofi/Aventis, Peloton Therapeutics, UpToDate, NCCN, Michael J. Hennessy Associates, Analysis Group, Kidney Cancer Journal, Clinical Care Options, Paltform Q, Navinata Healthcare, Harborside Press, ASCO, NEJM, Lancet Oncology, EMD Serono, HERON, Lilly, ESMO, NiKang Therapeutics, Kanaph Therapeutics, Infinity Pharmaceuticals, and Aravive Research Funding (inst.): Pfizer, Novartis, Merck, Exelixis , TRACON Pharma, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Peloton Therapeutics, Roche/Genentech, Celldex, Agensys, Eisai, Takeda, Prometheus, Ipsen, Corvus Pharmaceuticals, Cerulean Pharma, Seattle Genetics/Astellas, Bayer, Foundation Medicine, Roche, Calithera Biosciences, Analysis Group, NCI, GATEWAY for Cancer Research, and Congressionally Directed Medical Research Programs (DOD) Patents, Royalties, Other Intellectual Property (inst.): International Patent Application No. PCT/US2018/058430, entitled “Biomarkers of Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy, International Patent Application No. PCT/US2018/12209, entitled “PBRM1 Biomarkers Predictive of Anti-Immune Checkpoint Response Patents, Royalties, Other Intellectual Property: ctDNA technologies Travel, Accommodations, Expenses: Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, Bristol-Myers Squibb, Roche/Genentech, Eisai, Foundation Medicine, Cerulean Pharma, AstraZeneca, Exelixis, Prometheus, alligent, Ipsen, Corvus Pharmaceuticals, Lpath, Alexion Pharmaceuticals, Sanofi/Aventis, UpToDate, Peloton Therapeutics, NCCN, Michael J. Hennessy Associates, Analysis Group, Kidney Cancer Journal, Clinical Care Options, PlatformQ Health, Harborside Press, Navinata Healthcare, NEJM, Lancet Oncology, EMD Serono, HERON, Lilly, and ESMO Other Relationship: Medical writing and editorial assistance support may have been funded by Communications companies funded by pharmaceutical companies such as ClinicalThinking, Health Interactions, Envision Pharma Group, Fishawack Group of Companies, Parexel Disclaimer: 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.
Dr. Choueiri discusses the significance of the FDA approval of pembrolizumab as adjuvant therapy in renal cell carcinoma and key data from the pivotal phase 3 KEYNOTE-564 trial.
In 2015, when he was 48, Chuck was diagnosed with advanced (stage 4) renal cell carcinoma or kidney cancer. He had a cold and noticed blood in his urine. He credits the thoroughness of his primary care physician for immediately sending him for diagnostic tests where they discovered a massive tumor two days later. He is married to his high school sweetheart Liz, and they have 4 daughters He has undergone multiple surgeries and has participated in numerous clinical trials. He works as the vice president of business operations at the National Fire Protection Agency and is a life-long Boston sports fan and die-hard Boston College Eagles fan. See omnystudio.com/listener for privacy information.
PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Video Podcast
Go online to PeerView.com/GHE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In a new CME- and ABIM MOC-certified program on RCC from PeerView and the Kidney Cancer Research Alliance (KCCure), an expert faculty panel will share how to optimally select and sequence treatment regimens across multiple lines of therapy for patients with advanced RCC, talk about new options for resectable RCC, and discuss clinical trials involving novel therapies. Upon completion of this activity, participants should be better able to: Assess recent efficacy and safety data on new treatment approaches, including targeted TKIs, immuno-oncology (IO) agents, and novel combination approaches, for advanced renal cell carcinoma (RCC), Integrate recent clinical research findings on validated TKI and IO-based options into the development of individualized treatment plans for patients with newly diagnosed and previously treated advanced RCC, Recommend ongoing clinical trials assessing novel therapies and/or combination approaches for RCC patients in different disease and treatment settings, Implement practical strategies to mitigate and manage adverse events related to targeted and immune-based therapies for advanced RCC.
PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Audio Podcast
Go online to PeerView.com/GHE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In a new CME- and ABIM MOC-certified program on RCC from PeerView and the Kidney Cancer Research Alliance (KCCure), an expert faculty panel will share how to optimally select and sequence treatment regimens across multiple lines of therapy for patients with advanced RCC, talk about new options for resectable RCC, and discuss clinical trials involving novel therapies. Upon completion of this activity, participants should be better able to: Assess recent efficacy and safety data on new treatment approaches, including targeted TKIs, immuno-oncology (IO) agents, and novel combination approaches, for advanced renal cell carcinoma (RCC), Integrate recent clinical research findings on validated TKI and IO-based options into the development of individualized treatment plans for patients with newly diagnosed and previously treated advanced RCC, Recommend ongoing clinical trials assessing novel therapies and/or combination approaches for RCC patients in different disease and treatment settings, Implement practical strategies to mitigate and manage adverse events related to targeted and immune-based therapies for advanced RCC.
Go online to PeerView.com/GHE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In a new CME- and ABIM MOC-certified program on RCC from PeerView and the Kidney Cancer Research Alliance (KCCure), an expert faculty panel will share how to optimally select and sequence treatment regimens across multiple lines of therapy for patients with advanced RCC, talk about new options for resectable RCC, and discuss clinical trials involving novel therapies. Upon completion of this activity, participants should be better able to: Assess recent efficacy and safety data on new treatment approaches, including targeted TKIs, immuno-oncology (IO) agents, and novel combination approaches, for advanced renal cell carcinoma (RCC), Integrate recent clinical research findings on validated TKI and IO-based options into the development of individualized treatment plans for patients with newly diagnosed and previously treated advanced RCC, Recommend ongoing clinical trials assessing novel therapies and/or combination approaches for RCC patients in different disease and treatment settings, Implement practical strategies to mitigate and manage adverse events related to targeted and immune-based therapies for advanced RCC.
Go online to PeerView.com/GHE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In a new CME- and ABIM MOC-certified program on RCC from PeerView and the Kidney Cancer Research Alliance (KCCure), an expert faculty panel will share how to optimally select and sequence treatment regimens across multiple lines of therapy for patients with advanced RCC, talk about new options for resectable RCC, and discuss clinical trials involving novel therapies. Upon completion of this activity, participants should be better able to: Assess recent efficacy and safety data on new treatment approaches, including targeted TKIs, immuno-oncology (IO) agents, and novel combination approaches, for advanced renal cell carcinoma (RCC), Integrate recent clinical research findings on validated TKI and IO-based options into the development of individualized treatment plans for patients with newly diagnosed and previously treated advanced RCC, Recommend ongoing clinical trials assessing novel therapies and/or combination approaches for RCC patients in different disease and treatment settings, Implement practical strategies to mitigate and manage adverse events related to targeted and immune-based therapies for advanced RCC.
Go online to PeerView.com/GHE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In a new CME- and ABIM MOC-certified program on RCC from PeerView and the Kidney Cancer Research Alliance (KCCure), an expert faculty panel will share how to optimally select and sequence treatment regimens across multiple lines of therapy for patients with advanced RCC, talk about new options for resectable RCC, and discuss clinical trials involving novel therapies. Upon completion of this activity, participants should be better able to: Assess recent efficacy and safety data on new treatment approaches, including targeted TKIs, immuno-oncology (IO) agents, and novel combination approaches, for advanced renal cell carcinoma (RCC), Integrate recent clinical research findings on validated TKI and IO-based options into the development of individualized treatment plans for patients with newly diagnosed and previously treated advanced RCC, Recommend ongoing clinical trials assessing novel therapies and/or combination approaches for RCC patients in different disease and treatment settings, Implement practical strategies to mitigate and manage adverse events related to targeted and immune-based therapies for advanced RCC.
Go online to PeerView.com/GHE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In a new CME- and ABIM MOC-certified program on RCC from PeerView and the Kidney Cancer Research Alliance (KCCure), an expert faculty panel will share how to optimally select and sequence treatment regimens across multiple lines of therapy for patients with advanced RCC, talk about new options for resectable RCC, and discuss clinical trials involving novel therapies. Upon completion of this activity, participants should be better able to: Assess recent efficacy and safety data on new treatment approaches, including targeted TKIs, immuno-oncology (IO) agents, and novel combination approaches, for advanced renal cell carcinoma (RCC), Integrate recent clinical research findings on validated TKI and IO-based options into the development of individualized treatment plans for patients with newly diagnosed and previously treated advanced RCC, Recommend ongoing clinical trials assessing novel therapies and/or combination approaches for RCC patients in different disease and treatment settings, Implement practical strategies to mitigate and manage adverse events related to targeted and immune-based therapies for advanced RCC.
ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors who care for people with cancer. 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. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's podcast, 4 Cancer.Net Specialty Editors discuss new research in prostate, bladder, kidney, and testicular cancers presented at the 2021 Genitourinary Cancers Symposium, and 2021 ASCO Annual Meeting. This episode has been adapted from the recording of a live Cancer.Net webinar, held June 16th, 2021, and led by Dr. Neeraj Agarwal, Dr. Tian Zhang, Dr. Petros Grivas, and Dr. Timothy Gilligan. Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center. Dr. Zhang is an associate professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute. Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Institute. Full disclosures for Dr. Agarwal, Dr. Grivas, Dr. Zhang, and Dr. Gilligan are available at Cancer.Net. Greg Guthrie: So today, let's introduce our participants. First we have Dr. Neeraj Agarwal of Huntsman Cancer Institute and University of Utah and the Cancer.Net Specialty Editor for Prostate Cancer. Next we have Dr. Petros Grivas from Fred Hutchinson Cancer Research Center and University of Washington. He is the Specialty Editor for Cancer.Net for Bladder Cancer. Next we have Dr. Tian Zhang of Duke Cancer Institute. And she's our Cancer.Net Specialty Editor for Kidney Cancer. And last, we have Dr. Timothy Gilligan. He is with the Cleveland Clinical Taussig Cancer Institute and the Specialty Editor for Testicular Cancer. So to start off, we'll have Dr. Agarwal talking about prostate cancer. Dr. Agarwal: Thank you, Greg. It's such a privilege and honor to be here discussing these studies. So I would like to start with the first study, which was led by Dr. Stephen Freedland, a urologist at the Cedars-Sinai Medical Center in Los Angeles and was co-authored by me, Dr. Dan George, and many others. And here in this study, we present the utilization of therapies, which are associated and known to be associated with very significant, in fact, I would say dramatic improvement in overall survival, as shown by multiple randomized control trials over the period of the last 5 to 6 years. Just to take a step back for the audience, until 2014, standard treatment for metastatic castration-sensitive prostate cancer or newly diagnosed metastatic castration-sensitive prostate cancer used to be androgen deprivation therapy. And combining androgen deprivation therapy with those medications which were approved in the castration-resistant metastatic prostate cancer setting. So basically, using those drugs upfront led to dramatic improvement in overall survival with 33% to 35% reduction in risk of death across those clinical trials. So we actually wanted to look at the real-world utilization, so look at the real-world users of these medications in these patients who are being diagnosed with -- newly diagnosed metastatic prostate cancer in the United States. We also wanted to see how patients who belong to minority populations or racial minority populations, how they are being treated with these medications, which are backed by level 1 evidence. So this was a retrospective analysis of a Medicare database, more than 35,000 patients were included from 2009 to 2018. And we can see here a very representative patient population, predominantly white patients, 11.8% were African American, and 5% were Hispanic. And here are the results. From 2010 to 2014, the use of standard androgen deprivation therapy with bicalutamide, was used in 97% of patients. We did not have trials reporting by that. Let's go to 2015 to 2016. Docetaxel was already approved in this setting now, and we can see some patients received docetaxel, but a small minority of patients received docetaxel. And then let's move to 2018, which is 4 or 5 years after docetaxel data had been presented by Dr. Sweeney in the ASCO plenary session. And abirateron was approved in 2017, and we are still seeing even like almost 2 years after -- we are still seeing the vast majority of patients being treated with standard androgen deprivation therapy or standard deprivation therapy with bicalutamide. So 62% plus 19%, we are talking about almost 80% of patients still not being treated with standard of care treatment, which is androgen deprivation therapy plus docetaxel, or androgen deprivation therapy plus abiraterone at this point of time, and now we have 2 more drugs available, which include enzalutamide and apalutamide in this study. Another interesting thing was if you look at the patients who belong to minority populations, so let's look at African American patients compared to Caucasian patients. The use of intensified therapy was numerically lower. So in Caucasian patients, we are seeing higher use of intensified, as we call them, intensified therapy, or therapies which are considered standard of care, compared to African American men. So overall, the use was lower across the board, but if you look at African American men, the usage was even lower. So this is definitely concerning. I call it alarming, underutilization of life-prolonging therapy in patients who are being diagnosed with newly -- or new diagnosis of metastatic prostate cancer, and we definitely can improve this. We can definitely offer better care to our patients. It is not acceptable in my view to have 30% or less patients receiving standard of care therapies. So with that, I'll go to the next study. Greg Guthrie: Great, thanks. And this study is, “Health-related quality of life and patient-reported outcomes at final analysis of the TITAN study of apalutamide versus placebo in patients with metastatic castration-sensitive prostate cancer receiving androgen-deprivation therapy.” And you were the presenting author of this, Dr. Agarwal? Dr. Agarwal: Yes, Greg, thank you for giving the opportunity to present this study. And this is basically the continuation of the previous trial. I will not delve into in-depth analysis of these data. I just wanted to show that quality of life is not being impacted adversely by using intensified androgen deprivation therapy, so if you are using these drugs, which improves survival in a very significant fashion, and they are not being used in our patients, as we just saw in the previous study, what could be the reason? Is it the concerns about quality of life or adverse impact on quality of life? If that is the concern, this study, I think, helps refute those concerns. And in this study, which was a large study known as the TITAN trial, which led to approval of apalutamide for patients with hormone-sensitive or castration-sensitive metastatic prostate cancer and showed improved survival and radiographic progression-free and overall survival. We looked at quality of life data as reported by these patients, and these quality-of-life data were assessed by very standardized, validated scales known as FACT-P, or Functional Assessment of Cancer Therapy Prostate scale, or Brief Pain Inventory tool. And there are many other tools. So I will show you the results. And we can see here consistently there was no difference in quality of life as reported by the patients, or I would say any adverse impact on quality of life for these patients in any of these questions. As they were taking these questionnaires. So whether it was physical wellness, emotional wellness, functional well-being, social, or family, we go in and look at fatigue and there was no adverse impact on quality of life. At least from this perspective, we should not be concerned about using these drugs up front in our patients who have newly diagnosed metastatic prostate cancer. Greg Guthrie: Great. And so what does this mean for patients? Dr. Agarwal: From patient perspective, we can see here very clearly that using standardized tools, very validated tools, which have been used in multiple trials in the past, patients are not reporting any adverse impact on their quality of life when being treated with intensified androgen deprivation therapy. In this context, apalutamide. Greg Guthrie: Great. Alright. So let's move on to our next study, which is, “Phase 3 study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer.” The VISION trial. Dr. Agarwal: Thank you. In my view, this is 1 of the most important studies presented in the 2021 ASCO Annual Meeting. This study was a phase 3 study where 7,000 patients were recruited, and they had metastatic castration-resistant prostate cancer and had disease progression on a prior novel hormonal therapy such as enzalutamide or abiraterone and the patients had received a taxane chemotherapy. So at least 1 taxane chemotherapy was required before the trial, and the patient had to have disease progression on a novel hormone therapy. These patients were randomized in 2 to 1 fashion to a novel drug, which is a type of radiation, intravenous radiation, as I would explain to my patients, and this is known as beta radiation. And this is a novel radiotherapy where radiation particle, which is delivering beta radiation particle to the cancer cells, is tagged to a molecule, which binds with the prostate cancer cells. So I'm simplifying it for the sake of our patients. And this particle or this compound was added to standard of care therapy and patients were randomized to standard of care therapy versus standard of care therapy plus this new compound. And standard of care therapy was a novel hormonal therapy or anything which did not include chemotherapy or radium 223, which is another type of radiation particle, but a different kind of particle known as alpha particle. So in this study, radiographic progression-free survival and overall survival were primary endpoints. We can see here that the study met both primary endpoints. There was a significant improvement in radiographic progression-free survival with an almost 5 month, 5.4 months, to be precise, improvement in radiographic progression-free survival, with a 60% reduction in risk of disease progression or death. If you look at overall survival, it was also improved in a significant fashion in patients who received the new compound known as lutetium-PSMA-617, and the median survival was improved by 4 months with an approximately 40% reduction in risk of death. This was a well-tolerated drug overall, and if you look at hybrid side effects, treatment, and emergent side effects, there were 52.7% of patients in the experimental arm, and 38% in the control arm had those treatment-related side effects. So overall, Wwell-tolerated regimen with improved overall survival and radiographic progression. Thank you very much. Greg Guthrie: Thank you, Dr. Agarwal. This is really interesting, and it will be interesting to see if this treatment does change standard of care based on this research. Let's move on to Dr. Grivas and bladder cancer research. Let's see, so Dr. Grivas, your first study is, “Avelumab first-line maintenance for advanced urothelial carcinoma: analysis of clinical and genomic subgroups from the JAVELIN Bladder 100 trial.” And Dr. Grivas was a co-principal investigator in this trial and is senior author of the New England Journal of Medicine publication and co-author of this abstract. Go ahead, Dr. Grivas. Dr. Grivas: Thank you so much, Greg, and thank you to Cancer.Net for the opportunity, and thanks to the audience. We welcome questions. I would like to update the audience today about the data we saw at the ASCO meeting, and I would like to place this data in context, and I would remind the audience the JAVELIN Bladder 100 trial that changed clinical practice was initially presented last year at the ASCO Virtual Meeting 2020 by Professor Powles. And this particular trial tried to answer the following question: does the immunotherapy, especially the PD-L1 inhibitor avelumab, add value in patients who completed chemotherapy in the first-line setting of metastatic urothelial cancer compared to just best supportive care in terms of longer life, in terms of overall survival, and time until the cancer grows or death, progression-free survival? This is important because until this study came about last year, the practice was, in the setting of spread metastatic urothelial cancer, when the chemotherapy stops, was we cannot give it for a long time because of potential side effects. Usually you used to wait until the cancer grows back, it progresses, or grows. So this trial compared this approach, the best supportive care, versus the immunotherapy with avelumab and the best supportive care. This particular trial, so the significant improvement of life expectancy and overall survival as well as progression-free survival, time until progression of the cancer or death, in the patients that received this immunotherapy drug avelumab as a way to maintain or sustain the benefit that is seen with chemotherapy. So we call this a maintenance therapy approach because we tried to maintain or sustain the benefit with chemotherapy. I want to highlight that this was published in the New England Journal of Medicine and the audience can retrieve that from PubMed if one wants to read the manuscript. The bottom line is this trial changed practice, and we can go now to updates. We saw this in this particular meeting, ASCO 2021, and I think the main question was, are there any particular subsets of patients, different categories of patients, who benefit more from the avelumab maintenance approach, or does this benefit all the patients? And we saw at the ASCO meeting, we saw that the benefit with this immunotherapy appears consistent across the board, across different subcategories of groups of patients. And I think that it's important to point out that we looked at patients who had what we call local disease around the bladder, that was invading this area, and the pelvic side wall that was not amenable to surgical rejection and also patients with spread of the cancer in distant sites, what we call metastasis. And we look at patients who had a primary origin in the bladder or higher up in the urinary tract, what we call kidney pelvis, or ureter, and we call this upper urinary tract, versus the lower tract, which is the bladder, and we also look at patients who had metastatic spread in the lymph nodes only or other parts of the body. And with the bottom line, we saw that the benefit with the immunotherapy was consistent across the different groups of patients. So many patients benefit from this treatment, again, with variable degrees, variable magnitude of benefit, but overall, the bottom line is, take home message is if you have clinical factors or other molecular factors, we do not have a reliable, accurate tool to select which patients should go with avelumab, so we offer it nowadays in every patient who has no contraindication to get immunotherapy and has received some disease control. Meaning a response of the cancer or stabilization of the cancer with the chemotherapy phase. So that has real clinical implications, and I encourage the audience to discuss with their oncologist about the optimal roles of immunotherapy with this maintenance setting after chemotherapy when this is controlled with chemotherapy. Just for context here, I want to highlight the options the patients have in clinical practice. And when someone is diagnosed with spread urothelial cancer, they can be offered nowadays avelumab as a maintenance strategy to maintain the benefit of chemotherapy, and the other options include immunotherapy up front, like drugs like pembrolizumab or atezolizumab, and I will come back to that question how to select your treatment in my last slide. And I want to point out these are the options, and obviously clinical trials are always a great option for patients, and they should ask their oncologist about those options. So since I talked about immunotherapy, I want to point out that the ideal chemotherapy is cisplatin-based chemotherapy. Not everybody has enough fitness of the body to tolerate cisplatin. For those patients, we think cisplatin may be too much, we use carboplatin/gemcitabine, and we use avelumab maintenance in that scenario. What about immunotherapy after that? Is there data supporting that use? And the answer is yes. There is some data suggesting that immunotherapy can be an option for some of the patients, and in this particular slide, we update the data from another clinical trial. And I will let Greg, you can read the title of that. Greg Guthrie: Sure, so this study is, “First-line pembrolizumab in cisplatin-ineligible patients with advanced urothelial cancers response and survival results up to 5 years from the KEYNOTE-052 phase 2 study.” Dr. Grivas, you're a co-author on this study. Dr. Grivas: That's right, thank you, Greg. This trial presented longer follow up to see what happened in patients who received the immune checkpoint inhibitor anti-PD called pembrolizumab because they were not fit enough to get cisplatin chemotherapy. Keep in mind this was designed before the previous study I showed you presented the results and included patients who were not fit for cisplatin, but some of them could have been fit for carboplatin. There was no comparison here, everybody received pembrolizumab as a single agent, alone, and in this particular study, we would try to see the degree of shrinkage of the cancer and the overall response rate as well as how long people lived over time. So with longer follow-up, by the way, we published this study in the Lancet Oncology years ago, and we have longer follow-up, and what you see here is a degree of shrinkage of the cancer, what we call overall response rate, was about 29% in what we call all comers, and it was higher size of tumor shrinkage in patients with high PD-L1 expression. PD-L1 is this brake of the immune system, the checkpoint of the immune system and highly expressive measured by particular assay that pembrolizumab works better in those patients. However, some patients even with low PD-L1 measured by this CPS score I put in the slide still might have benefits, so the take-home message here is there is a particular proportion of patients who can benefit from the checkpoint inhibitor pembrolizumab. PD-L1 can be used in that setting to help decide between chemotherapy and immunotherapy. However, we have not compared directly the chemotherapy followed by the available maintenance with immunotherapy up front, so this question is still lingering. However, if the patient has a response shrinkage to pembrolizumab, many of those patients may have a long-lasting response. We tried to figure out with research how can we predict who is going to benefit more from this treatment as a matter of ongoing research. Greg Guthrie: Dr. Grivas, can you really quickly define CPS for our audience? Dr. Grivas: Absolutely. Great question. CPS is a tool we use in the pathology labs to measure the PD-L1 expression. It can be measured by different assessing antibodies, and the pathologists use a score to define if the PD-L1 is high or low. In this particular study, CPS of 10 or higher defines PD-L1 high expression, CPS below 10 defines PD-L1 low expression, and this appears to have some association with a chance of the tumor shrinking with immunotherapy with pembrolizumab. Greg Guthrie: Great. Thanks, Dr. Grivas. So our last study is, “Pembrolizumab versus investigator's choice of paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer: 5-year follow-up from the phase 3 KEYNOTE-045 trial.” Dr. Grivas Very quickly, this study compared immunotherapy, pembrolizumab, the anti-PDL1, compared to chemotherapy with paclitaxel, docetaxel, or vinflunine, the latter one is in Europe, after progression of cancer growth on platinum-based chemotherapy. This was published in the New England Journal of Medicine a few years ago, and pembrolizumab prolonged survival, people lived longer compared to the chemotherapy. And this longer follow-up presented by Dr. Bellmunt and colleagues, showed the sustained results with follow-up, this population of patients had already received cisplatin-based chemotherapy and the cancer progressed, growth, despite that chemo, and in those patients, pembrolizumab appears to produce better results compared to this salvage chemotherapy shown in that slide. And this has implications because immunotherapy can be used in those patients after progression on platinum-based chemotherapy. And just to wrap up here the discussion, I just want to give the options to the patients, see if someone has a new urothelial cancer, options include cisplatin/gemcitabine, or if someone is not fit enough for cisplatin, carboplatin/gemcitabine, and both of those scenarios can be followed by avelumab, and those with shrinking or stable disease, patients who have progression on platinum-based chemotherapy can get pembrolizumab and of course other options available. We can go into another podcast, and I encourage the audience to look and discuss with their oncologist about those options, and the take home message, the clinical trials is what got us here, and I recommend clinical trials to be discussed with your oncologist. Thank you so much, and I'll be happy to take questions. Greg Guthrie: Thanks, Dr. Grivas. So we're going to move on to Dr. Zhang, who is going to talk about kidney cancer. So our first study today is, “Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: a randomized, double-blind, phase III KEYNOTE-564 study.” Dr. Zhang: Thanks, Greg. I'm really excited to be here today and thanks, everyone, for joining. KEYNOTE-564 was presented at the ASCO plenary by our colleague Dr. Toni K. Choueiri, and this is a highly anticipated study in the adjuvant space for kidney cancer and enrolled patients with high-risk clear cell kidney cancer who had undergone either nephrectomy or a metastastectomy, removing their few sites of metastatic disease and treating those patients with either pembrolizumab for up to a year or placebo. And the endpoint was disease-free survival, and enough events had occurred by this ASCO for us to see the primary results. So the overall -- the study was positive. For the primary endpoint, disease-free survival improvement was met with a hazard ratio of 0.68 and the estimated disease-free survival rate at 2 years was 77% for patients treated with pembrolizumab versus 68% for patients treated with placebo. The overall survival favored pembrolizumab, but it was not yet statistically significant, and follow-up will be needed. Overall, we see an improvement in disease-free survival delaying time until recurrence for patients treated with pembrolizumab, and this was the first study in this adjuvant space showing checkpoint inhibition has a role in adjuvant treatment of renal cell carcinoma. Greg Guthrie: Thanks, Dr. Zhang. Our next study is, “Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma: results from 42-month follow-up of KEYNOTE-426.” Dr. Zhang: This study, KEYNOTE-426, we are all very familiar with. Pembrolizumab and axitinib has been used for the last 2 years in the first-line treatment of clear cell metastatic kidney cell cancer, and it's a longer-term follow-up, more events and more understanding of what happens to these patients once they're treated in a longer term, so primary endpoints of course of this phase 3 study were progression-free survival and overall survival. When we're looking at this medium duration of follow-up at 42 months, so about 3 and a half years, pembrolizumab and axitinib improved both median overall survival as well as median progression-free survival. We'd point out that the -- at the 3 and a half year mark, the overall survival rate for patients treated with the combination was about 57.5%. And the progression-free survival rate was about 25%, so about a third of patients had not had progression of disease at 3 and a half years. Which is quite meaningful if they can stay on their first-line treatment for that long. The objective response was 60%, and of note, the complete response rate had been updated to about 10%. So there are some patients that do have delayed complete responses. And no new safety signals were observed. So overall, certainly still provides a lot of evidence to treat with pembrolizumab and axitinib for patients in the front-line setting. Greg Guthrie: Great. And our last study here is, “Health-related quality of life analysis from the phase 3 CLEAR trial of lenvatinib plus pembrolizumab or everolimus versus sunitinib for patients with advanced renal cell carcinoma.” Dr. Zhang: This was the phase III trial in first-line treatment of metastatic clear cell kidney cancer that was reported at GU ASCO in February of 2020, and it was a 3-arm randomization to lenvatinib with everolimus in the standard study, and lenvatinib with pembrolizumab or sunitinib alone, and we saw the efficacy data in February, and here we're seeing the quality of life outcomes, and looking at how patients are doing, patient-reported outcomes on these treatments. And so with multiple quality of life measures, we're seeing improvements in patients that had better disease-related scores of symptoms when treated with lenvatinib and pembrolizumab versus sunitinib. We're seeing pain scores improve and patients having less diarrhea, appetite loss, when we're comparing against sunitinib. Of note, it's hard to specifically tie a particular symptom, if that's improved, because they've had better disease control or if it's more from the treatment side effect itself. So still hard to tease out a causality in these quality of life measures, but overall, improvement in patients' quality of life when treated with lenvatinib and pembrolizumab. And certainly provides some more data for patients receiving this combination. And so I just wanted to highlight our ongoing phase 3 combination trials and first-line metastatic kidney cancer. PIVOT-09 with bempegaldesleukin has completed accrual in the first triplet of COSMIC-313 with ipilimumab, nivolumab and cabozantinib has completed accrual, so the actively enrolling studies currently are PEDIGREE and PROBE. These are studies that are being carried out in the cancer cooperative groups, as well as a triplet belzutifan lenvatinib with pembrolizumab, a study that Merck is running and all 3 very important studies we will continue to learn from and answer some important, clinically relevant sequencing treatment discontinuation, nephrectomy side effect questions. Thanks to everybody. Greg Guthrie: We have 1 more. So, “Clinical activity of durvalumab and savolitinib in MET-driven, metastatic papillary renal cancer.” Dr. Zhang: Dr. Rodriguez from Spain presented this of papillary renal cell carcinoma treated with savolitinib and durvalumab, and specifically looked at the MET-driven subset of 14 patients out of these 42 patients. The efficacy primary end point was objective response rate. And of note, and median progression-free survival for the 42 patients who were all treated, it was 4.9 months and in MET-driven disease, so savolitinib targets MET, so MET-driven disease was 10.5 months and the median overall survival in everyone was 14 months, versus MET-driven was 27 months, and also higher response rates for patients with MET-driven disease. So I think personally, hypothesis generating, we will likely be seeing more trials with durvalumab and savolitinib in MET-driven papillary renal cell carcinoma. Greg Guthrie: Thank you, again, Dr. Zhang. And Dr. Gilligan, we're going to talk about some testicular cancer research now, and the first study is, “Testicular cancer in the cisplatin era: causes of death and mortality rates in a population-based cohort.” Dr. Gilligan: So this study was looking at what happens with testicular cancer patients who are cured of their cancer, are they at risk of dying of other causes? They looked at over 5,000 men treated between 1980 and 2009, so it's important to recognize that some of the treatments given back then are a little different than the way they're given now. And it looked at the risk of death from causes other than testis cancer compared to men without testicular cancer in the general population, and the concerning finding from this study, and it's not the first study to report this, was that the risk of non-testicular cancer death, that is, death from other causes, was increased by about 28% in men who had been treated with radiation therapy and about 23% in men treated with chemotherapy. There's a risk of non-testicular cancer death, the risk, excuse me, was doubled in those whose treatment included both. So it was higher with either radiation or chemo and it was actually 100% higher or double than both those who had chemotherapy and radiation. As you got more chemotherapy, the risk went up. There was no trend towards the increase with just 1 or 2 cycles. We started to see the increase with 3 cycles, and it became statistically significant with 4 cycles. But there wasn't much difference between 3 and 4 in terms of the absolute number that was seen. In terms of death from other cancers, so why is this happening? Other cancers are a major issue after chemotherapy or radiation. Again, the risk was increased 60% after radiation therapy and 43% after chemotherapy, and those who got both, the risk of cancer was 3 times higher than the general population. So that's in men who had chemotherapy plus radiation therapy. Fortunately, there are not a lot of men who get both of those treatments anymore. Non-cancer deaths increased 17% after chemo and 55% of treatment included both. So the risk for non-cancer deaths was not as high as the risk for death from secondary malignancies. Interestingly, the risk of suicide increased 63% in men treated with chemotherapy. That's not affecting as many men as those other numbers, even though 63% number looks high, but it is a concern. Those treated only with surgery did not have an increased risk of non-testicular cancer death. What does this mean for patients? It really means when we can use surgical treatments instead of chemotherapy or radiation as an additional incentive to try do that, and what that may mean is there should be a larger role for retroperitoneal lymph node dissection as an alternative to chemotherapy or radiation therapy. Secondly, for patients getting chemotherapy, it's important to minimize the number of cycles of chemo as long as we're not sacrificing long-term cure rates, because the biggest risk of death is dying from the cancer, but that means limiting to the 3 cycles instead of 4 cycles is probably a good idea, and I think it's an argument to use 3 cycles of BPE instead of 4 cycles of EP because it's really the etoposide and the cisplatin that is linked to the secondary cancer risk, not the bleomycin, as far as we know. And then lastly, we need to pay attention to the mental health needs of men treated with chemotherapy. That there is more emotional distress and we're seeing here a higher risk of suicide. Greg Guthrie: So our second trial is the, “SEMS trial: result of a prospective multi-institutional phase 2 clinical trial of surgery in early metastatic seminoma.” Dr. Gilligan: So if we're going to use more retroperitoneal dissection and less chemotherapy or radiation, 1 place to do that is in stage 1 and stage 2 seminoma, and many centers around the country have started doing that, and this was a trial that looked at that approach. So these are men who normally would be treated with chemotherapy, 3 cycles of BEP, or radiation therapy to the back of the abdomen and part of the pelvis potentially. This study looked at the small number of patients, 55 men, low volume, stage 2 seminoma up to 3 centimeters of size and maximum dimension. And what they reported of those men undergoing retroperitoneal lymph node dissection, 10 relapsed, so 18% relapsed after median follow-up of 24 months, they were all alive at the end of the study. No deaths. 8 of 10 relapses were treated with chemotherapy, and 2 were treated with additional [surgery]. Out of the 55 men, 8 ended up getting chemotherapy. Normally, all of them would have gotten either chemo or radiation. Relapse-free survival was 87%, overall survival was 100%. Seven (7) patients developed complications after RPLND and 5 of them were mild. Two (2) were more severe. So it's a well-tolerated treatment, if it's done at a large volume center, it's worth noting that the centers participating in the study were large volume centers. Again, if not treated with RPLND, all of these men would have gotten chemo or radiation. The relapse rate after chemotherapy or radiation is about 5%. So the relapse risk is higher after surgery, but in the sense, if we take 100 men with early stage 2 seminoma and do an RPLND instead of chemo or radiation, we can spare 80% of them the long-term effects of chemotherapy or radiation. Alternatively, if the priority is simply to prevent a relapse, radiation therapy and chemotherapy are more effective at that, the relapse risk being 5% but at the cost of long-term side effects from chemotherapy or radiation. Bottom line there is an additional treatment option for low volume stage 2 seminoma for men who prioritize avoiding the complications of chemotherapy or radiation therapy. Both of which are associated with an increased risk of death from other causes. The price we pay for that is the relapse risk is higher with RPLND compared to the other approaches. Not all centers are going to be offering this, but major centers that do a lot of testicular cancer, this is becoming a new treatment option. With the caveat that we have less experience with this approach. This is a relatively small study. And we have a lot more experience with chemotherapy or radiation. I don't think there's a one size fits all here, but I think patients should talk about it with their doctor. If they have early-stage seminoma, they should talk about surgery as an alternative to radiation or chemo. Greg Guthrie: Here we go. “Surveillance after complete response in patients with metastatic non-seminomatous germ-cell tumor.” Dr. Gilligan: So this study is looking at the question, if you take a man who has retroperitoneal lymph nodes that are enlarged and metastatic non-seminomatous testis cancer with lymphadenopathy in the back of the abdomen and you put them through chemotherapy and at the end, all retroperitoneal nodes are now within normal limits, normal size nodes, and no bigger than 10 millimeters or 1 centimeter, do we need to do a retroperitoneal lymph node dissection on those patients? Some centers recommend it and some don't. This looked at 388 men in that situation. They were put on surveillance. These men did not undergo the post-chemo RPLND. Two years survival, overall survival was 97.8%. Two-year progression-free survival was at 90%, 34 patients relapsed, and 10 of the men died. Men who did relapse had surgery, chemotherapy, or both as subsequent treatment. There's a prior similar study that was multicenter that had longer follow-up of 5 years, and they reported of ;161 men who had a complete response to the first-line chemo, 10 relapsed (that's 6%) and none died. If we combine these 2 studies together, the bottom line is you would have to perform a post-chemotherapy retroperitoneal dissection, which is a big operation, on about 550 men to prevent potentially at most 44 relapses and 10 deaths. We don't know if we would prevent or how many of those relapses and deaths we would prevent. But there's a lot of operations with a relatively low yield. In the future, we hope to have blood tests that will tell us which men need surgery. And even right now, we're close to the point that we have blood tests that will detect residual cancer. And the chance is we worry about residual cancer in these patients and we don't have the blood test to pick it up. But the bottom line is in the meantime, the preferred management strategy is surveillance rather than surgery for most men. There's some men for whom RPLND may make sense in the center in this setting and some centers that will probably continue to recommend it for most men. I think this data really casts doubt on whether we ought to be doing this operation in these men as a routine practice as opposed to an exceptional practice for men who have particular characteristics. Thank you. Greg Guthrie: Thank you, Dr. Gilligan. And now we can move on to answering some questions. What is the average time expected to see a decline in PSA in patients treated with lutetium-177 PSMA? Dr. Agarwal: I think this a great question and I think we're waiting for the manuscript published to go through the nuances of those data. Right now, what Dr. Michael Morris from Memorial Sloane-Kettering presented were the high-level data on pre-survival and overall survival and some secondary endpoints. We are anxiously waiting the full data in the form of a manuscript. And until then, I will not be able to answer that question. I would like to add that usually the median time, if you look at how -- for how long patients were receiving lutetium, it was 5 to 6 months. If I -- if my recollection is correct. Greg Guthrie: Is radiation required prior to initiating chemo if there's tumor presence? And Dr. Gilligan, you responded. “We rarely use radiation therapy for testicular cancer at this time. Sometimes it is used for stage 1 or stage 2 seminoma as primary treatment instead of chemotherapy.” And I'll just read these aloud for our viewers here. If a patient has both prostate and bladder cancer, how do you decide which therapy should take priority, also, is the CPS typically included on the biopsy report? And Dr. Grivas, you responded, which I'll read here. “This is a bit of a complicated scenario that requires detailed discussion with a urologist and medical oncologist. Regarding CPS, the possible role is only in the first-line setting of metastatic disease to help somewhat decide between chemotherapy followed by avelumab maintenance and immunotherapy. However, it's not a perfect biomarker and not part of the pathology report, it's a special test that requires specific ordering.” I have a question for you, Dr. Zhang. Why do combination treatments seem to work better in kidney cancer? Wouldn't you have more side effects because you're taking 2 drugs at the same time? Dr. Zhang: It's an interesting question. You know, our immunotherapy backbones seem to have good treatment benefit for these immune responsive diseases. The VEGF inhibitors that blocked blood vessel formation for many of our patients with clear cell kidney cancer, they tend to have an immunomodulatory role, so if we normalize blood vessels in the tumor microenvironment, the thought is that the T cells and immune cells can actually get into that space more readily. And so many of these blood vessel blockers are hypothesized to have increased immunomodulatory times of behaviors and the combination actually can be more effective than either agent alone, and we've certainly seen that in practice and really excited to see these combination strategies thrive and be standard of care for our patients now and first-line treatment. For the side effect question, you know, I do think that sometimes we do have to tease out which of the side effects is related to the oral treatment, the blood vessel blocker versus the immune therapy. But it's often experienced oncologists who are able to manage these side effects. We can try to tailor and see which of the side effects is due to which treatment and how to reduce or hold treatments when necessary. Greg Guthrie: Great. I just got a follow-up question for you, Dr. Zhang. Are there any studies for papillary type kidney cancer with sarcoma? Dr. Zhang: I would assume you're asking about sarcomatoid renal cell carcinoma within papillary, so for papillary type of kidney cancers, there are ongoing studies. For example, with FH mutations and FMH loss. For sarcomatoid disease, this is a special type of histology that can occur with any of our actual histologies of kidney cancer. And we know from our phase 3 trials in clear cell sarcomatoid renal cells that these tend to respond to the immunotherapy combinations. And so I would urge using an immune therapy combination in patients who had sarcomatoid renal cell carcinoma. Greg Guthrie: Dr. Agarwal, here is a question for you. There were several studies in here that showed many patients did not receive combination ADT with other novel therapies, which you describe as the standard of care, including the one you discussed. Is this something that patients should proactively bring up with their doctors? Dr. Agarwal: Fantastic question. I'm so glad you asked. The answer is yes: It is our responsibility as physicians and providers, but it doesn't hurt if our patients are educated and challenge us in our decision-making. It is a shared decision-making, it is not the doctor's decision. In my view, it's the patient's decision with help from the doctors. So, yes, please go do it. Doctors usually welcome that. Greg Guthrie: Great. Dr. Grivas: I see one for Dr. Gilligan about surveillance imaging that just popped up. [Is there any data on the benefits vs. risks for imaging based surveillance (CT, MRI, none) for longer-term follow-up periods (e.g. 2+ years)?] Dr. Gilligan: Yeah, they're asking whether there's data on benefit versus risk for imaging-based surveillance and it's actually a very timely question in the sense that we're starting to get data that MRI is very accurate for this. And may likely become a substitute for CT scans at some point in the future. This is something we talk about a lot in terms of surveillance for testicular cancer patients, can we switch to MRI from CT because CT has ionization that can cause other cancers, and MRI does not. The good news is it looks like with current CT scanning, which is lower dose than older CT scanning, the risk of cancer from the CT scan seems really miniscule. Ultimately, it would be great to get it down to 0 and not do them, but we're still doing them. The switch to MRI is being held up by the fact that when you go in and get an imaging study for surveillance, your scans get looked at by a radiologist and also by the oncologist and all of us who do a lot of testicular cancer have multiple stories of catching stuff that the radiologist missed, and they also catch stuff that we miss. It goes both directions, and we're having 2 different people read the films to get a more accurate read. With MRI, most oncologists are not competent to read an MRI well and some radiologists are not great, and the centers where they have excellence have shown that MRIs are just as good as CT scans if read by fully qualified people. And the concern is: are they going to be skillfully read? So the switch to MRI will happen in the future, and I have spoken with people very recently about this that are practicing around the country and the people I talked to were not ready to make the switch because of the concern that stuff might get missed. And I think we can be reassured with the modern lower-dose CT scans, the risk seems to be quite small, and I look forward in the future to making that switch at some point. Greg Guthrie: And I think that's going to be our last question this afternoon. Thank you to all our participants for sharing this great research with us, as well as your expertise, it's been a real pleasure on this live webinar here. ASCO: Thank you Dr. Agarwal, Dr. Grivas, Dr. Zhang, and Dr. Gilligan. You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate. This presentation is provided solely for informational purposes. The ideas and opinions expressed in this presentation do not necessarily reflect the views of the American Society of Clinical Oncology (ASCO) or its affiliates. The mention of any product, service, or therapy in this presentation should not be construed as an endorsement of any product, service, or therapy mentioned. The information herein does not constitute medical or legal advice, and is not intended for use in the diagnosis or treatment of individual conditions or as a substitute for consultation with a licensed medical professional. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the presentation or any errors or omissions. © ASCO 2021, all rights reserved.
Go online to PeerView.com/QEY860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The therapeutic landscape of renal cell carcinoma (RCC) continues to expand rapidly with the addition of novel multi-targeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. The long-term data supporting the efficacy of dual checkpoint blockade, together with further follow-up reported for established immunotherapy-TKI partners, as well as new efficacious combinations, has increased the number of treatment choices in the frontline setting of advanced RCC. Oncologists and other healthcare professionals who manage patients with RCC are being called upon to apply these novel immune and targeted strategies in a patient-centric manner. During this PeerView CME/MOC-certified activity, an expert faculty panel will share the clinical science and current evidence on novel targeted and immunotherapeutic strategies in the upfront and previously treated advanced RCC settings. Upon completion of this activity, participants should be better able to: Summarize the latest efficacy and safety data on new treatment approaches for advanced and/or resectable renal cell carcinoma (RCC), including targeted tyrosine kinase inhibitors, immune checkpoint inhibitors, and novel combination approaches, Select optimal frontline treatment options, such as dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors, for individual patients with advanced RCC based on the latest clinical evidence and relevant patient- and disease-related factors, Apply new clinical trial evidence to the selection and sequencing of novel agents and combination therapies for individual patients with advanced RCC that have progressed after one or more previous lines of therapy, taking into account patient treatment history and comorbidities, Employ effective strategies to proactively mitigate and manage adverse events related to targeted and immune-based therapies for advanced RCC.
Go online to PeerView.com/QEY860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The therapeutic landscape of renal cell carcinoma (RCC) continues to expand rapidly with the addition of novel multi-targeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. The long-term data supporting the efficacy of dual checkpoint blockade, together with further follow-up reported for established immunotherapy-TKI partners, as well as new efficacious combinations, has increased the number of treatment choices in the frontline setting of advanced RCC. Oncologists and other healthcare professionals who manage patients with RCC are being called upon to apply these novel immune and targeted strategies in a patient-centric manner. During this PeerView CME/MOC-certified activity, an expert faculty panel will share the clinical science and current evidence on novel targeted and immunotherapeutic strategies in the upfront and previously treated advanced RCC settings. Upon completion of this activity, participants should be better able to: Summarize the latest efficacy and safety data on new treatment approaches for advanced and/or resectable renal cell carcinoma (RCC), including targeted tyrosine kinase inhibitors, immune checkpoint inhibitors, and novel combination approaches, Select optimal frontline treatment options, such as dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors, for individual patients with advanced RCC based on the latest clinical evidence and relevant patient- and disease-related factors, Apply new clinical trial evidence to the selection and sequencing of novel agents and combination therapies for individual patients with advanced RCC that have progressed after one or more previous lines of therapy, taking into account patient treatment history and comorbidities, Employ effective strategies to proactively mitigate and manage adverse events related to targeted and immune-based therapies for advanced RCC.
Go online to PeerView.com/QEY860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The therapeutic landscape of renal cell carcinoma (RCC) continues to expand rapidly with the addition of novel multi-targeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. The long-term data supporting the efficacy of dual checkpoint blockade, together with further follow-up reported for established immunotherapy-TKI partners, as well as new efficacious combinations, has increased the number of treatment choices in the frontline setting of advanced RCC. Oncologists and other healthcare professionals who manage patients with RCC are being called upon to apply these novel immune and targeted strategies in a patient-centric manner. During this PeerView CME/MOC-certified activity, an expert faculty panel will share the clinical science and current evidence on novel targeted and immunotherapeutic strategies in the upfront and previously treated advanced RCC settings. Upon completion of this activity, participants should be better able to: Summarize the latest efficacy and safety data on new treatment approaches for advanced and/or resectable renal cell carcinoma (RCC), including targeted tyrosine kinase inhibitors, immune checkpoint inhibitors, and novel combination approaches, Select optimal frontline treatment options, such as dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors, for individual patients with advanced RCC based on the latest clinical evidence and relevant patient- and disease-related factors, Apply new clinical trial evidence to the selection and sequencing of novel agents and combination therapies for individual patients with advanced RCC that have progressed after one or more previous lines of therapy, taking into account patient treatment history and comorbidities, Employ effective strategies to proactively mitigate and manage adverse events related to targeted and immune-based therapies for advanced RCC.
Go online to PeerView.com/QEY860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The therapeutic landscape of renal cell carcinoma (RCC) continues to expand rapidly with the addition of novel multi-targeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. The long-term data supporting the efficacy of dual checkpoint blockade, together with further follow-up reported for established immunotherapy-TKI partners, as well as new efficacious combinations, has increased the number of treatment choices in the frontline setting of advanced RCC. Oncologists and other healthcare professionals who manage patients with RCC are being called upon to apply these novel immune and targeted strategies in a patient-centric manner. During this PeerView CME/MOC-certified activity, an expert faculty panel will share the clinical science and current evidence on novel targeted and immunotherapeutic strategies in the upfront and previously treated advanced RCC settings. Upon completion of this activity, participants should be better able to: Summarize the latest efficacy and safety data on new treatment approaches for advanced and/or resectable renal cell carcinoma (RCC), including targeted tyrosine kinase inhibitors, immune checkpoint inhibitors, and novel combination approaches, Select optimal frontline treatment options, such as dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors, for individual patients with advanced RCC based on the latest clinical evidence and relevant patient- and disease-related factors, Apply new clinical trial evidence to the selection and sequencing of novel agents and combination therapies for individual patients with advanced RCC that have progressed after one or more previous lines of therapy, taking into account patient treatment history and comorbidities, Employ effective strategies to proactively mitigate and manage adverse events related to targeted and immune-based therapies for advanced RCC.
Go online to PeerView.com/QEY860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The therapeutic landscape of renal cell carcinoma (RCC) continues to expand rapidly with the addition of novel multi-targeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. The long-term data supporting the efficacy of dual checkpoint blockade, together with further follow-up reported for established immunotherapy-TKI partners, as well as new efficacious combinations, has increased the number of treatment choices in the frontline setting of advanced RCC. Oncologists and other healthcare professionals who manage patients with RCC are being called upon to apply these novel immune and targeted strategies in a patient-centric manner. During this PeerView CME/MOC-certified activity, an expert faculty panel will share the clinical science and current evidence on novel targeted and immunotherapeutic strategies in the upfront and previously treated advanced RCC settings. Upon completion of this activity, participants should be better able to: Summarize the latest efficacy and safety data on new treatment approaches for advanced and/or resectable renal cell carcinoma (RCC), including targeted tyrosine kinase inhibitors, immune checkpoint inhibitors, and novel combination approaches, Select optimal frontline treatment options, such as dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors, for individual patients with advanced RCC based on the latest clinical evidence and relevant patient- and disease-related factors, Apply new clinical trial evidence to the selection and sequencing of novel agents and combination therapies for individual patients with advanced RCC that have progressed after one or more previous lines of therapy, taking into account patient treatment history and comorbidities, Employ effective strategies to proactively mitigate and manage adverse events related to targeted and immune-based therapies for advanced RCC.
PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Audio Podcast
Go online to PeerView.com/QEY860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The therapeutic landscape of renal cell carcinoma (RCC) continues to expand rapidly with the addition of novel multi-targeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. The long-term data supporting the efficacy of dual checkpoint blockade, together with further follow-up reported for established immunotherapy-TKI partners, as well as new efficacious combinations, has increased the number of treatment choices in the frontline setting of advanced RCC. Oncologists and other healthcare professionals who manage patients with RCC are being called upon to apply these novel immune and targeted strategies in a patient-centric manner. During this PeerView CME/MOC-certified activity, an expert faculty panel will share the clinical science and current evidence on novel targeted and immunotherapeutic strategies in the upfront and previously treated advanced RCC settings. Upon completion of this activity, participants should be better able to: Summarize the latest efficacy and safety data on new treatment approaches for advanced and/or resectable renal cell carcinoma (RCC), including targeted tyrosine kinase inhibitors, immune checkpoint inhibitors, and novel combination approaches, Select optimal frontline treatment options, such as dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors, for individual patients with advanced RCC based on the latest clinical evidence and relevant patient- and disease-related factors, Apply new clinical trial evidence to the selection and sequencing of novel agents and combination therapies for individual patients with advanced RCC that have progressed after one or more previous lines of therapy, taking into account patient treatment history and comorbidities, Employ effective strategies to proactively mitigate and manage adverse events related to targeted and immune-based therapies for advanced RCC.
Go online to PeerView.com/QEY860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The therapeutic landscape of renal cell carcinoma (RCC) continues to expand rapidly with the addition of novel multi-targeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. The long-term data supporting the efficacy of dual checkpoint blockade, together with further follow-up reported for established immunotherapy-TKI partners, as well as new efficacious combinations, has increased the number of treatment choices in the frontline setting of advanced RCC. Oncologists and other healthcare professionals who manage patients with RCC are being called upon to apply these novel immune and targeted strategies in a patient-centric manner. During this PeerView CME/MOC-certified activity, an expert faculty panel will share the clinical science and current evidence on novel targeted and immunotherapeutic strategies in the upfront and previously treated advanced RCC settings. Upon completion of this activity, participants should be better able to: Summarize the latest efficacy and safety data on new treatment approaches for advanced and/or resectable renal cell carcinoma (RCC), including targeted tyrosine kinase inhibitors, immune checkpoint inhibitors, and novel combination approaches, Select optimal frontline treatment options, such as dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors, for individual patients with advanced RCC based on the latest clinical evidence and relevant patient- and disease-related factors, Apply new clinical trial evidence to the selection and sequencing of novel agents and combination therapies for individual patients with advanced RCC that have progressed after one or more previous lines of therapy, taking into account patient treatment history and comorbidities, Employ effective strategies to proactively mitigate and manage adverse events related to targeted and immune-based therapies for advanced RCC.
PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Video Podcast
Go online to PeerView.com/QEY860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The therapeutic landscape of renal cell carcinoma (RCC) continues to expand rapidly with the addition of novel multi-targeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. The long-term data supporting the efficacy of dual checkpoint blockade, together with further follow-up reported for established immunotherapy-TKI partners, as well as new efficacious combinations, has increased the number of treatment choices in the frontline setting of advanced RCC. Oncologists and other healthcare professionals who manage patients with RCC are being called upon to apply these novel immune and targeted strategies in a patient-centric manner. During this PeerView CME/MOC-certified activity, an expert faculty panel will share the clinical science and current evidence on novel targeted and immunotherapeutic strategies in the upfront and previously treated advanced RCC settings. Upon completion of this activity, participants should be better able to: Summarize the latest efficacy and safety data on new treatment approaches for advanced and/or resectable renal cell carcinoma (RCC), including targeted tyrosine kinase inhibitors, immune checkpoint inhibitors, and novel combination approaches, Select optimal frontline treatment options, such as dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors, for individual patients with advanced RCC based on the latest clinical evidence and relevant patient- and disease-related factors, Apply new clinical trial evidence to the selection and sequencing of novel agents and combination therapies for individual patients with advanced RCC that have progressed after one or more previous lines of therapy, taking into account patient treatment history and comorbidities, Employ effective strategies to proactively mitigate and manage adverse events related to targeted and immune-based therapies for advanced RCC.
In our exclusive interview, Dr. Choueiri and Dr. Motzer discuss the clinical implications of the phase 3 CheckMate-9ER trial in advanced renal cell carcinoma and how to best use the combination in practice.
Toni Choueiri (@DrChoueiri), MD, Dana-Farber Cancer Institute, joins the show to guest host a discussion with Rana McKay (@DrRanaMcKay), MD, UC San Diego, and Alicia Morgans (@CaPsurvivorship), MD, MPH, Northwestern University, on the practice-changing abstracts presented at the 2020 ASCO-GU virtual meeting. The trio weigh the importance and real-world implications of the ACIS study for mCRPC, EV-301 for advanced or metastatic urothelial carcinoma as well as CheckMate 274 for muscle-invasive disease, CLEAR for first-line treatment of advanced RCC, and so much more.
Robert Figlin, MD, Steven Spielberg Family Chair in Hematology-Oncology, Cedars-Sinai Medical Center and Toni Choueiri, MD, Director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute, discuss clinical progress in renal cell carcinoma (RCC)
Robert Figlin, MD, Steven Spielberg Family Chair in Hematology-Oncology, Cedars-Sinai Medical Center and Toni Choueiri, MD, Director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute, discuss clinical progress in renal cell carcinoma (RCC)
Details of the study......
Co-hosts Charu Aggarwal and Jack West are joined by Dr. Toni Choueiri to discuss the role of twitter for education, mentorship and a platform for sharing credible information.
Go online to PeerView.com/QRQ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The therapeutic landscape of renal cell carcinoma (RCC) continues to expand rapidly with the addition of novel targeted, immune-based, and tyrosine kinase inhibitors (TKIs) to the treatment armamentarium. Most recently, these advances have included the validation of novel combinatorial approaches, such as dual checkpoint inhibition and immunotherapy plus targeted agents (which have led to FDA approvals). Oncology professionals are increasingly challenged to adopt a more nuanced and personalized approach to selecting and sequencing the available treatment options throughout the advanced RCC continuum while taking relevant patient-, disease-, and treatment-related factors into account. During this PeerView Live CME/MOC-certified web broadcast, an expert faculty panel in RCC will share insights on recent clinical trends and how to effectively navigate a complex therapeutic landscape to leverage the potency of newer agents across different disease settings. Upon completion of this activity, participants should be better able to: Summarize updated efficacy and safety evidence on the use of multi-targeted tyrosine kinase inhibitors/anti-VEGF agents, immune checkpoint inhibitors, and novel combination approaches in the management of advanced and/or resectable renal cell carcinoma (RCC), Select individualized frontline treatment regimens utilizing targeted and immune-based options for patients with advanced RCC based on relevant patient- and disease-related characteristics, Develop regimens with novel components for patients with pretreated advanced RCC over multiple lines of therapy based on consideration of prior treatment history and patient comorbidities, Manage treatment-related complications with targeted agents and immunotherapy in patients with RCC.
Go online to PeerView.com/QRQ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The therapeutic landscape of renal cell carcinoma (RCC) continues to expand rapidly with the addition of novel targeted, immune-based, and tyrosine kinase inhibitors (TKIs) to the treatment armamentarium. Most recently, these advances have included the validation of novel combinatorial approaches, such as dual checkpoint inhibition and immunotherapy plus targeted agents (which have led to FDA approvals). Oncology professionals are increasingly challenged to adopt a more nuanced and personalized approach to selecting and sequencing the available treatment options throughout the advanced RCC continuum while taking relevant patient-, disease-, and treatment-related factors into account. During this PeerView Live CME/MOC-certified web broadcast, an expert faculty panel in RCC will share insights on recent clinical trends and how to effectively navigate a complex therapeutic landscape to leverage the potency of newer agents across different disease settings. Upon completion of this activity, participants should be better able to: Summarize updated efficacy and safety evidence on the use of multi-targeted tyrosine kinase inhibitors/anti-VEGF agents, immune checkpoint inhibitors, and novel combination approaches in the management of advanced and/or resectable renal cell carcinoma (RCC), Select individualized frontline treatment regimens utilizing targeted and immune-based options for patients with advanced RCC based on relevant patient- and disease-related characteristics, Develop regimens with novel components for patients with pretreated advanced RCC over multiple lines of therapy based on consideration of prior treatment history and patient comorbidities, Manage treatment-related complications with targeted agents and immunotherapy in patients with RCC.
PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Audio Podcast
Go online to PeerView.com/QRQ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The therapeutic landscape of renal cell carcinoma (RCC) continues to expand rapidly with the addition of novel targeted, immune-based, and tyrosine kinase inhibitors (TKIs) to the treatment armamentarium. Most recently, these advances have included the validation of novel combinatorial approaches, such as dual checkpoint inhibition and immunotherapy plus targeted agents (which have led to FDA approvals). Oncology professionals are increasingly challenged to adopt a more nuanced and personalized approach to selecting and sequencing the available treatment options throughout the advanced RCC continuum while taking relevant patient-, disease-, and treatment-related factors into account. During this PeerView Live CME/MOC-certified web broadcast, an expert faculty panel in RCC will share insights on recent clinical trends and how to effectively navigate a complex therapeutic landscape to leverage the potency of newer agents across different disease settings. Upon completion of this activity, participants should be better able to: Summarize updated efficacy and safety evidence on the use of multi-targeted tyrosine kinase inhibitors/anti-VEGF agents, immune checkpoint inhibitors, and novel combination approaches in the management of advanced and/or resectable renal cell carcinoma (RCC), Select individualized frontline treatment regimens utilizing targeted and immune-based options for patients with advanced RCC based on relevant patient- and disease-related characteristics, Develop regimens with novel components for patients with pretreated advanced RCC over multiple lines of therapy based on consideration of prior treatment history and patient comorbidities, Manage treatment-related complications with targeted agents and immunotherapy in patients with RCC.
Go online to PeerView.com/QRQ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The therapeutic landscape of renal cell carcinoma (RCC) continues to expand rapidly with the addition of novel targeted, immune-based, and tyrosine kinase inhibitors (TKIs) to the treatment armamentarium. Most recently, these advances have included the validation of novel combinatorial approaches, such as dual checkpoint inhibition and immunotherapy plus targeted agents (which have led to FDA approvals). Oncology professionals are increasingly challenged to adopt a more nuanced and personalized approach to selecting and sequencing the available treatment options throughout the advanced RCC continuum while taking relevant patient-, disease-, and treatment-related factors into account. During this PeerView Live CME/MOC-certified web broadcast, an expert faculty panel in RCC will share insights on recent clinical trends and how to effectively navigate a complex therapeutic landscape to leverage the potency of newer agents across different disease settings. Upon completion of this activity, participants should be better able to: Summarize updated efficacy and safety evidence on the use of multi-targeted tyrosine kinase inhibitors/anti-VEGF agents, immune checkpoint inhibitors, and novel combination approaches in the management of advanced and/or resectable renal cell carcinoma (RCC), Select individualized frontline treatment regimens utilizing targeted and immune-based options for patients with advanced RCC based on relevant patient- and disease-related characteristics, Develop regimens with novel components for patients with pretreated advanced RCC over multiple lines of therapy based on consideration of prior treatment history and patient comorbidities, Manage treatment-related complications with targeted agents and immunotherapy in patients with RCC.
PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Video Podcast
Go online to PeerView.com/QRQ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The therapeutic landscape of renal cell carcinoma (RCC) continues to expand rapidly with the addition of novel targeted, immune-based, and tyrosine kinase inhibitors (TKIs) to the treatment armamentarium. Most recently, these advances have included the validation of novel combinatorial approaches, such as dual checkpoint inhibition and immunotherapy plus targeted agents (which have led to FDA approvals). Oncology professionals are increasingly challenged to adopt a more nuanced and personalized approach to selecting and sequencing the available treatment options throughout the advanced RCC continuum while taking relevant patient-, disease-, and treatment-related factors into account. During this PeerView Live CME/MOC-certified web broadcast, an expert faculty panel in RCC will share insights on recent clinical trends and how to effectively navigate a complex therapeutic landscape to leverage the potency of newer agents across different disease settings. Upon completion of this activity, participants should be better able to: Summarize updated efficacy and safety evidence on the use of multi-targeted tyrosine kinase inhibitors/anti-VEGF agents, immune checkpoint inhibitors, and novel combination approaches in the management of advanced and/or resectable renal cell carcinoma (RCC), Select individualized frontline treatment regimens utilizing targeted and immune-based options for patients with advanced RCC based on relevant patient- and disease-related characteristics, Develop regimens with novel components for patients with pretreated advanced RCC over multiple lines of therapy based on consideration of prior treatment history and patient comorbidities, Manage treatment-related complications with targeted agents and immunotherapy in patients with RCC.
Go online to PeerView.com/QRQ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The therapeutic landscape of renal cell carcinoma (RCC) continues to expand rapidly with the addition of novel targeted, immune-based, and tyrosine kinase inhibitors (TKIs) to the treatment armamentarium. Most recently, these advances have included the validation of novel combinatorial approaches, such as dual checkpoint inhibition and immunotherapy plus targeted agents (which have led to FDA approvals). Oncology professionals are increasingly challenged to adopt a more nuanced and personalized approach to selecting and sequencing the available treatment options throughout the advanced RCC continuum while taking relevant patient-, disease-, and treatment-related factors into account. During this PeerView Live CME/MOC-certified web broadcast, an expert faculty panel in RCC will share insights on recent clinical trends and how to effectively navigate a complex therapeutic landscape to leverage the potency of newer agents across different disease settings. Upon completion of this activity, participants should be better able to: Summarize updated efficacy and safety evidence on the use of multi-targeted tyrosine kinase inhibitors/anti-VEGF agents, immune checkpoint inhibitors, and novel combination approaches in the management of advanced and/or resectable renal cell carcinoma (RCC), Select individualized frontline treatment regimens utilizing targeted and immune-based options for patients with advanced RCC based on relevant patient- and disease-related characteristics, Develop regimens with novel components for patients with pretreated advanced RCC over multiple lines of therapy based on consideration of prior treatment history and patient comorbidities, Manage treatment-related complications with targeted agents and immunotherapy in patients with RCC.
The group attempts to put the data into context with the other available combinations.
Professor Tom Powles, Dr. Brian Rini and Dr. Toni Choueiri discuss the evolving landscape in Boston, and meetings such as ASCO and ESMO in 2020.
Electrons produce thrust! Wait, what? They're so small though? Electric propulsion has been propelling spacecraft for decades! We don't see it during rocket launches for a number of reasons, listen in to learn why! Press play for the brain candy that is Electric Propulsion. Music from filmmusic.io "Tyrant" by Kevin MacLeod (incompetech.com) License: CC BY (creativecommons.org/licenses/by/4.0/) Sources: ASAP Science, director. The Periodic Table Song. The Periodic Table Song, 2018, www.youtube.com/watch?v=rz4Dd1I_fX0. Choueiri, EY. “A Critical History of Electric Propulsion: The First 50 Years (1906–1956).” A Critical History of Electric Propulsion: The First 50 Years (1906–1956), 2004, alfven.princeton.edu/publications/choueiri-jpp-2004. “Deep Space 1 Asteroid Flyby.” Deep Space 1 Asteroid Flyby, NASA, July 1999, www.jpl.nasa.gov/news/press_kits/ds1asteroid.pdf. “Deep Space 1.” NASA, NASA, www.jpl.nasa.gov/missions/deep-space-1-ds1/. Dunbar, Brian. “Ion Propulsion.” NASA, NASA, 18 Aug. 2015, www.nasa.gov/centers/glenn/about/fs21grc.html. “Electrically Powered Spacecraft Propulsion.” Wikipedia, Wikimedia Foundation, 24 Feb. 2020, en.wikipedia.org/wiki/Electrically_powered_spacecraft_propulsion. FalconSat-5 - EoPortal Directory - Satellite Missions, directory.eoportal.org/web/eoportal/satellite-missions/f/falconsat-5. Gallimore, Alec, and Arthur Thurnau. “The Physics of Spacecraft Hall-Effect Thrusters.” The Physics of Spacecraft Hall-Effect Thrusters, University of Michigan, 2008, www.aps.org/units/dfd/meetings/upload/Gallimore_APSDFD08.pdf. Goebel, Dan M, and Ira Katz. Fundamentals of Electric Propulsion: Ion and Hall Thrusters . JPL Space Science and Technology Series, 2008. “GRC - SPACE ELECTRIC ROCKET TEST I (SERT I).” NASA, NASA, www.grc.nasa.gov/WWW/ion/past/60s/sert1.htm. “GRC - SPACE ELECTRIC ROCKET TEST II (SERT II).” NASA, NASA, www.grc.nasa.gov/WWW/ion/past/70s/sert2.htm. “Ion Thruster.” Wikipedia, Wikimedia Foundation, 13 Mar. 2020, en.wikipedia.org/wiki/Ion_thruster. “List of Spacecraft with Electric Propulsion.” Wikipedia, Wikimedia Foundation, 27 Feb. 2020, en.wikipedia.org/wiki/List_of_spacecraft_with_electric_propulsion. “Our Engine.” Our Engine | Ad Astra Rocket, www.adastrarocket.com/aarc/VASIMR. “Plasma Propulsion Engine.” Wikipedia, Wikimedia Foundation, 29 Feb. 2020, en.wikipedia.org/wiki/Plasma_propulsion_engine. “Rocket Propulsion.” NASA, NASA, www.grc.nasa.gov/WWW/K-12/airplane/rocket.html. SciShow Space, director. The Electric Thruster That Could Send Humans to Mars. The Electric Thruster That Could Send Humans to Mars, 2019, www.youtube.com/watch?v=Isn7FoJvtRY. SciShow Space, director. Thrusters That Eat Teflon! | Pulsed Plasma Thrusters. Thrusters That Eat Teflon! | Pulsed Plasma Thrusters, 2018, www.youtube.com/watch?v=6HUOumDJeAQ. “Scout (Rocket Family).” Wikipedia, Wikimedia Foundation, 2 Mar. 2020, en.wikipedia.org/wiki/Scout_(rocket_family). “SERT 2.” Gunter's Space Page - Information on Spaceflight, Launch Vehicles and Satellites, space.skyrocket.de/doc_sdat/sert-2.htm. “Solar Electric Propulsion.” NASA, NASA, www1.grc.nasa.gov/space/sep/#factsheet. “Solar Electric Propulsion: NASA's Engine to Mars and Beyond.” SpaceFlight Insider, 28 Feb. 2016, www.spaceflightinsider.com/missions/human-spaceflight/solar-electric-propulsion-nasas-engine-mars-beyond/. Sovey, James S., et al. “Ion Propulsion Development Projects in U.S.: Space Electric Rocket Test I to Deep Space 1.” Journal of Propulsion and Power, vol. 17, no. 3, 2001, pp. 517–526., doi:10.2514/2.5806. “SSOE - SSOE Resources - File Not Found.” Pitt, www.engineering.pitt.edu/First-Year/First-Year-Conference/_Library/Dubendorf-Pineiro-Steen/.
TRANSCRIPT Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll. The Genitourinary Cancer Symposium hosted by ASCO in San Francisco revealed some significant clinical developments, and here to discuss key takeaways from the meeting is Dr. Karen Knudsen, program chair of the symposium. Dr. Knudsen is the enterprise director of the NCI-designated Sidney Kimmel Cancer Center at Jefferson at Thomas Jefferson University and Executive Vice President of oncology services at Jefferson Health. Dr. Knudsen, welcome to the Daily News Podcast. Dr. Knudsen: Thank you so much for having me. It's really a pleasure to get a chance to discuss all of the things that were revealed at the 2020 ASCO GU. ASCO Daily News: Dr. Knudsen, do you have any conflicts of interest that you'd like to disclose, which are relevant to our conversation? Dr. Knudsen: If I do have conflicts of interest, I don't think they're relevant for the conversation. But I like to disclose them anyway. As the cancer center director, it's something all of us are trying to pay more attention to. So I do have advisory and consultant positions with CellCentric and Genentech. I've had ad hoc advisory board positions in the last two years with Sanofi, Janssen, Novartis, and Celgene, and research support from CellCentric and Celgene. ASCO Daily News: All right, thanks Dr. Knudsen. Well, the Genitourinary Cancer Symposium showcased a lot of interesting presentations and insights on topics across GU malignancies. So what are your key takeaways from the meeting? Dr. Knudsen: So this was really an exciting meeting for us, and the way that we put together the program was aligned to our theme, which is, in pursuit of patient-centered care. And the program committee and steering committee really worked together to try to decide how the 2020 program should come about. And it was to take all of the things that were and are fantastic about ASCO to you and take it even further in a couple of different directions. Dr. Knudsen: One is to incorporate really the latest science, the latest evidence for some of the new agents and new interventions that we're seeing develop for GU malignancies, and also look to the future of things that are coming. The second was an emphasis on multidisciplinary teams, so effective integration of urology, medical oncology, and radiation oncology as related to GU cancers, but also the translational science behind the new findings and seeing those come together. Dr. Knudsen: And then the last was a focus on quality of life. As we've had all these new interagents and new interventions introduced over the last few years in the GU malignancy field, we felt it was really important for us to ensure that we're addressing impact on quality of life, including but not limited to financial toxicity throughout the meeting. And I think those elements were really achieved by dissection of the program, but also, we've heard just tremendously positive feedback from attendees about that additional incorporation and thoughtfulness within the meeting. Dr. Knudsen: So you know, kind of keeping that in mind, I think that some of the key takeaways are that the pace of our field is really moving quickly with regard to innovative imaging, combinations, especially novel combinations using immunotherapy as a backbone. We heard about new endpoints, PSS2, new biomarkers, and incorporation of targeted agents. So across all of the GU malignancies, there was this feeling that the pace has really accelerated for new opportunities for detection and intervention. Dr. Knudsen: In order to also really address what some of those new possibilities are, we had something quite different this year. We had the FDA with us in a, quote unquote, meet the regulators session to talk about some of these new technologies, new endpoints. And they actually walked us through a previous example of something that had come to light in the last few years in the GU field, which is incorporating the MSF or metastasis-free survival endpoint into GU malignancy trials. And that was a really important one. Dr. Knudsen: We also had some great reminders about how to ensure that our science and our clinical trials are tending to both statistical and clinical relevance. Fantastic statistical talk from Dr. Sides, who walked us through some of the ways that we can sharpen our focus on ensuring that we're drawing the right conclusions from the trials and the preclinical studies that we cover. Dr. Knudsen: And attendant to the theme of the meeting, we had a really fantastic keynote lecture from Dr. Dave Penson at Vanderbilt on financial toxicity and the impact on quality of life, as well as other endpoints, including patient-related outcomes and the overall outcomes from new interventions. He educated us about coping behaviors that patients engage in that may shift their compliance for cancer care and certainly, as may be related to other adverse events, and really shared with us some striking data about the number of patients that may be depleting their total net worth after a cancer diagnosis. So that part was really a call to arms to have all of us help attend to educating the patient as much as possible about financial ramifications, as well as other ramifications of therapies as they're introduced. So really, fantastic science, moving very quickly, and now we're ready to address some of the other ramifications of the newer interventions that we're introducing. ASCO Daily News: Speaking of new interventions, were there advances reported that would likely support new standards of care moving forward? Dr. Knudsen: There were. I think there-- you know, there were a number of advances that we're going to want to really track carefully over this next year. So advances in imaging were prominently discussed at the meeting-- when to use next generation imaging and taking into account disease state and clinical scenarios. Advances in standard of care are likely to also include-- we heard a lot about this at the meeting-- an increased incorporation of genetics, including both somatic and germline alteration. Dr. Knudsen: Dr. Castro gave us a really fantastic talk about the importance of profiling both somatic and germline alterations in patients, especially patients with advanced disease or who are at risk for aggressive disease, and showed us some compelling data about the limitations and ramifications of only looking at one, either somatic or germline. And that's probably not serving the patient as well as we could-- and gave us some very strong examples, especially with regard to DNA repair mutations, about how to incorporate this and to tailor therapy. Dr. Knudsen: I think that we'll see some changes coming in the future with regard to gene signatures and biomarkers. For example, even just in the prostate space, we heard about a 22 gene signature from Dr. Feng, which may predict who is going to need more aggressive care, as well as from Dr. Klotz with regard to non-coding RNAs and their ability to predict prostate cancer behavior. Dr. Knudsen: So this is actually a really interesting session, because we got into the dynamics of how we actually bring this to a change to [INAUDIBLE] where one of these signatures become standard of care, given the long-term follow-up that's really required to understand how these signatures inform prostate cancer behavior. So there was actually quite some healthy debate on that within the ASCO GU meeting. Dr. Knudsen: More forward thinking to later on was with some discussions with Dr. Beltran on epigenetics and how that may additionally influence our ability to predict behavior. But I think what I would say is probably the third and really interesting advance that we heard about at this meeting was our ability to use liquid biopsy and to have cell-free DNA or circulating tumor DNA inform the mechanisms of resistance that may be emerging in a particular tumor, and how we may treat that patient by anticipating and forwarding resistance. So a lot of really fantastic talks incorporated ctDNA into their discussions. Dr. Wyatt really stands out there in one of his discussions about the limitations of using circulating tumor DNA, but how promising this is with regard to giving concordance with what tumor lesions actually look like. So these are some technologies that are not quite ready yet to be incorporated as standard of care, but it's coming quickly. Dr. Knudsen: The future is really near, and so those are, I'd say, were some of the forward-thinking things that we really discussed, which, of course, complemented the exciting trial data that we saw, things that have been reported out and are likely to give new approvals and new interventions for GU malignancies in the near term. ASCO Daily News: You spoke about the prostate space a few moments ago. So I'm wondering, did any GU fields stand out more than others at this meeting? Dr. Knudsen: You know, I think each of the fields have had significant progress, as evidenced by some of the clinical trials that we heard about. So for example, in the clear cell renal carcinoma space, there was a lot of excitement over Dr. Choueiri's talk looking at a new target. So there was a Phase 1/2 trial for a first in class agent that's targeting a protein called HIF-2 alpha. And utilization of this oral HIF-2 alpha inhibitor and advanced clear cell renal carcinoma. Dr. Knudsen: So in this particular study, this new agent and the idea of targeting HIF-2 alpha actually emanated from what was the basis of the Nobel Prize in this last year with regard to understanding the factors that drive hypoxia and that are so important in this disease. And what was really remarkable about that Phase 1/2 trial is that there were objective responses seen in all of the different risk categories. So of course, the favorable category, but also the intermediate and poor risk category patients benefited from this agent. Dr. Knudsen: And so this is really, I think, one to watch. There's a large Phase 3 trial, as we understand it, on the way for this agent. So you know, clear cell-- that was just one of the things that we talked about. In the bladder cancer space, there was the NEOBLADE study, which is a neoadjuvant chemotherapy study, which was really interesting and was the basis of a lot of discussion as well, because the primary endpoint may not have actually achieved the benefit, which is a path CR. But there was improved PSS and overall survival as well in those patients. So that's also something really for us to watch and gives us new thoughts about what neoadjuvant chemotherapy might look like in bladder cancer. Dr. Knudsen: Another trial I think that was really interesting was the STOMP trial from Dr. Ost. So the primary endpoint for this study was something we don't always think about, which is androgen deprivation therapy free survival. That was really what was being tracked. And this is an interesting trial design. It wasn't designed to actually change practice, but to lay the foundation for a large Phase 3. And really, the question there for which the evidence looks quite interesting is, does metastasis direct to therapy improve this endpoint? Does ADT free survival? So I think that's one that was very forward-thinking type of strategy. Dr. Knudsen: And then not to underserve radiation oncology, because it was also featured very prominently at the meeting, and there were a lot of exciting results in a number of different formats. But the chip trial reported this long-term follow-up of a Phase 3 study looking at conventional versus hyperfractionated high dose radiation therapy in prostate cancer. And this was really a really good news outcome in that type of fractionation strategy appears to continue to be effective in these patients that require long-term follow-up. And certainly, prostate cancer at this stage is that category. So large number of trials that are on the cusp of being practice changing, and I just got a chance to mention a few. But in my view, all of the GU malignancies had these kinds of breakthroughs throughout the meeting that were reported. ASCO Daily News: That sounds very promising. And just finally, are there any other new agents in development or treatment approaches that really caught your attention and looked promising for the future? Dr. Knudsen: Yeah, I think there are. So in the prostate cancer space, there was significant discussion-- And this, I'm sure, will continue into GU ASCO 2021-- about the treatment of oligometastases and that oligometastases are really not the same as low volume disease. And that is going to be increasingly important for us as a field to understand the biology of oligomets. This may cause us to really redefine, as we can now image oligometastases much better with PSMA, attached agents just to redefine the M0 state and reexamine our thoughts about the trials that have happened in the past, or, perhaps, these patients actually were not at the MDR stage. Dr. Knudsen: So that's one part of the oligometastases story. The other is, what is the impact of treating oligometastases? This is really where I think the field is moving. It's grappling with understanding that, and getting those trials to start to report out, I think, is going to be a really important thing for us to watch. In the muscle invasive bladder space, we talked and heard about the BLASST-1 trial from Dr. Gupta, which I think was also pretty exciting, exciting results with neoadjuvant, nivolumab, which [INAUDIBLE], and there was a report of the PCR in almost half of those patients. Think it was just under half of those patients-- really exciting. Dr. Knudsen: SGFR3 got a lot of discussion as a new target for bladder cancer, and there's a preview of what a Phase 3 trial might look like. But then there are also some studies that were really back to basics. They were incredibly important. So Dr. Plimack from Fox Chase Cancer Center here in Philadelphia gave a spectacular talk on side effect management. And this was for frontline treatment of renal cell carcinoma. Dr. Knudsen: And what she reminded us of is something incredibly important-- that strong side effects management, effective side effects management keeps patients on therapy and keeps them responding longer, and that we should not really undervalue this. It's something that's an important aspect of managing patients with advanced GU malignancies. And so as much as breakthroughs of new targets, new combinations, new ways to treat, new ways to image, but also, back to the patient centricity. Managing-- in this case, managing their side effects is a great way to get a better outcome. So important things to remember. ASCO Daily News: Absolutely. Well, I want to thank you, Dr. Knudsen, for sharing these interesting highlights from the GU Cancer Symposium. Dr. Knudsen: My pleasure. ASCO Daily News: And to our listeners, thank you for tuning in to the ASCO Daily News Podcast. If you're enjoying the content, please rate and review us on Apple Podcasts. 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. The following represent disclosure information provided by the guest(s) of this podcast: Dr. Karen Knudsen Consulting or Advisory Role: CellCentric and Genentech. Ad hoc advisory board positions in the last two years with Sanofi, Janssen, Novartis, and Celgene, and research support from CellCentric and Celgene.
PeerView Immunology & Transplantation CME/CNE/CPE Video Podcast
Go online to PeerView.com/KWJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The treatment armamentarium for advanced renal cell carcinoma (RCC) has undergone rapid expansion with the validation of novel multitargeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. More recently, the emergence of dual checkpoint blockade and immunotherapy-TKI combinations in RCC has increased the number of treatment choices in the frontline setting, allowed for greater flexibility when selecting second-line agents, and sparked additional research into TKI and immune checkpoint inhibitor options in earlier disease settings. In the wake of these advances, understanding how to effectively select and sequence newer regimens through multiple lines of therapy while ensuring safe usage is crucial to maximize beneficial patient outcomes throughout the advanced RCC continuum. This unique “How I Think, How I Treat” educational on-demand activity, based on an event held adjunct to the 18th International Kidney Cancer Symposium, features personal insights from leading kidney cancer experts on how they are adapting their own practice based on the evidence supporting optimized care in advanced RCC in the context of patient-, disease-, and treatment-specific factors, as well as how the innovations fueling modern approaches to care are improving outcomes for patients with RCC. Upon completion of this activity, participants should be better able to: Assess the latest evidence and clinical implications of novel approaches, including new multitargeted tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Select optimal frontline treatment options among TKIs and combination approaches (dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors) for individual patients with advanced RCC based on relevant patient- and disease-related characteristics, including in the context of clinical trial enrollment, Apply validated targeted therapy and immunotherapy options effectively for patients with pretreated advanced RCC through multiple lines of therapy that reflect considerations of prior treatment history and patient comorbidities, Employ effective strategies to prevent and/or manage treatment-related complications with multitargeted TKIs and immune checkpoint inhibitor therapy in patients with RCC
Go online to PeerView.com/KWJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The treatment armamentarium for advanced renal cell carcinoma (RCC) has undergone rapid expansion with the validation of novel multitargeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. More recently, the emergence of dual checkpoint blockade and immunotherapy-TKI combinations in RCC has increased the number of treatment choices in the frontline setting, allowed for greater flexibility when selecting second-line agents, and sparked additional research into TKI and immune checkpoint inhibitor options in earlier disease settings. In the wake of these advances, understanding how to effectively select and sequence newer regimens through multiple lines of therapy while ensuring safe usage is crucial to maximize beneficial patient outcomes throughout the advanced RCC continuum. This unique “How I Think, How I Treat” educational on-demand activity, based on an event held adjunct to the 18th International Kidney Cancer Symposium, features personal insights from leading kidney cancer experts on how they are adapting their own practice based on the evidence supporting optimized care in advanced RCC in the context of patient-, disease-, and treatment-specific factors, as well as how the innovations fueling modern approaches to care are improving outcomes for patients with RCC. Upon completion of this activity, participants should be better able to: Assess the latest evidence and clinical implications of novel approaches, including new multitargeted tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Select optimal frontline treatment options among TKIs and combination approaches (dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors) for individual patients with advanced RCC based on relevant patient- and disease-related characteristics, including in the context of clinical trial enrollment, Apply validated targeted therapy and immunotherapy options effectively for patients with pretreated advanced RCC through multiple lines of therapy that reflect considerations of prior treatment history and patient comorbidities, Employ effective strategies to prevent and/or manage treatment-related complications with multitargeted TKIs and immune checkpoint inhibitor therapy in patients with RCC
PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Audio Podcast
Go online to PeerView.com/KWJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The treatment armamentarium for advanced renal cell carcinoma (RCC) has undergone rapid expansion with the validation of novel multitargeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. More recently, the emergence of dual checkpoint blockade and immunotherapy-TKI combinations in RCC has increased the number of treatment choices in the frontline setting, allowed for greater flexibility when selecting second-line agents, and sparked additional research into TKI and immune checkpoint inhibitor options in earlier disease settings. In the wake of these advances, understanding how to effectively select and sequence newer regimens through multiple lines of therapy while ensuring safe usage is crucial to maximize beneficial patient outcomes throughout the advanced RCC continuum. This unique “How I Think, How I Treat” educational on-demand activity, based on an event held adjunct to the 18th International Kidney Cancer Symposium, features personal insights from leading kidney cancer experts on how they are adapting their own practice based on the evidence supporting optimized care in advanced RCC in the context of patient-, disease-, and treatment-specific factors, as well as how the innovations fueling modern approaches to care are improving outcomes for patients with RCC. Upon completion of this activity, participants should be better able to: Assess the latest evidence and clinical implications of novel approaches, including new multitargeted tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Select optimal frontline treatment options among TKIs and combination approaches (dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors) for individual patients with advanced RCC based on relevant patient- and disease-related characteristics, including in the context of clinical trial enrollment, Apply validated targeted therapy and immunotherapy options effectively for patients with pretreated advanced RCC through multiple lines of therapy that reflect considerations of prior treatment history and patient comorbidities, Employ effective strategies to prevent and/or manage treatment-related complications with multitargeted TKIs and immune checkpoint inhibitor therapy in patients with RCC
Go online to PeerView.com/KWJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The treatment armamentarium for advanced renal cell carcinoma (RCC) has undergone rapid expansion with the validation of novel multitargeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. More recently, the emergence of dual checkpoint blockade and immunotherapy-TKI combinations in RCC has increased the number of treatment choices in the frontline setting, allowed for greater flexibility when selecting second-line agents, and sparked additional research into TKI and immune checkpoint inhibitor options in earlier disease settings. In the wake of these advances, understanding how to effectively select and sequence newer regimens through multiple lines of therapy while ensuring safe usage is crucial to maximize beneficial patient outcomes throughout the advanced RCC continuum. This unique “How I Think, How I Treat” educational on-demand activity, based on an event held adjunct to the 18th International Kidney Cancer Symposium, features personal insights from leading kidney cancer experts on how they are adapting their own practice based on the evidence supporting optimized care in advanced RCC in the context of patient-, disease-, and treatment-specific factors, as well as how the innovations fueling modern approaches to care are improving outcomes for patients with RCC. Upon completion of this activity, participants should be better able to: Assess the latest evidence and clinical implications of novel approaches, including new multitargeted tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Select optimal frontline treatment options among TKIs and combination approaches (dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors) for individual patients with advanced RCC based on relevant patient- and disease-related characteristics, including in the context of clinical trial enrollment, Apply validated targeted therapy and immunotherapy options effectively for patients with pretreated advanced RCC through multiple lines of therapy that reflect considerations of prior treatment history and patient comorbidities, Employ effective strategies to prevent and/or manage treatment-related complications with multitargeted TKIs and immune checkpoint inhibitor therapy in patients with RCC
Go online to PeerView.com/KWJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The treatment armamentarium for advanced renal cell carcinoma (RCC) has undergone rapid expansion with the validation of novel multitargeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. More recently, the emergence of dual checkpoint blockade and immunotherapy-TKI combinations in RCC has increased the number of treatment choices in the frontline setting, allowed for greater flexibility when selecting second-line agents, and sparked additional research into TKI and immune checkpoint inhibitor options in earlier disease settings. In the wake of these advances, understanding how to effectively select and sequence newer regimens through multiple lines of therapy while ensuring safe usage is crucial to maximize beneficial patient outcomes throughout the advanced RCC continuum. This unique “How I Think, How I Treat” educational on-demand activity, based on an event held adjunct to the 18th International Kidney Cancer Symposium, features personal insights from leading kidney cancer experts on how they are adapting their own practice based on the evidence supporting optimized care in advanced RCC in the context of patient-, disease-, and treatment-specific factors, as well as how the innovations fueling modern approaches to care are improving outcomes for patients with RCC. Upon completion of this activity, participants should be better able to: Assess the latest evidence and clinical implications of novel approaches, including new multitargeted tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Select optimal frontline treatment options among TKIs and combination approaches (dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors) for individual patients with advanced RCC based on relevant patient- and disease-related characteristics, including in the context of clinical trial enrollment, Apply validated targeted therapy and immunotherapy options effectively for patients with pretreated advanced RCC through multiple lines of therapy that reflect considerations of prior treatment history and patient comorbidities, Employ effective strategies to prevent and/or manage treatment-related complications with multitargeted TKIs and immune checkpoint inhibitor therapy in patients with RCC
PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Video Podcast
Go online to PeerView.com/KWJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The treatment armamentarium for advanced renal cell carcinoma (RCC) has undergone rapid expansion with the validation of novel multitargeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. More recently, the emergence of dual checkpoint blockade and immunotherapy-TKI combinations in RCC has increased the number of treatment choices in the frontline setting, allowed for greater flexibility when selecting second-line agents, and sparked additional research into TKI and immune checkpoint inhibitor options in earlier disease settings. In the wake of these advances, understanding how to effectively select and sequence newer regimens through multiple lines of therapy while ensuring safe usage is crucial to maximize beneficial patient outcomes throughout the advanced RCC continuum. This unique “How I Think, How I Treat” educational on-demand activity, based on an event held adjunct to the 18th International Kidney Cancer Symposium, features personal insights from leading kidney cancer experts on how they are adapting their own practice based on the evidence supporting optimized care in advanced RCC in the context of patient-, disease-, and treatment-specific factors, as well as how the innovations fueling modern approaches to care are improving outcomes for patients with RCC. Upon completion of this activity, participants should be better able to: Assess the latest evidence and clinical implications of novel approaches, including new multitargeted tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Select optimal frontline treatment options among TKIs and combination approaches (dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors) for individual patients with advanced RCC based on relevant patient- and disease-related characteristics, including in the context of clinical trial enrollment, Apply validated targeted therapy and immunotherapy options effectively for patients with pretreated advanced RCC through multiple lines of therapy that reflect considerations of prior treatment history and patient comorbidities, Employ effective strategies to prevent and/or manage treatment-related complications with multitargeted TKIs and immune checkpoint inhibitor therapy in patients with RCC
Go online to PeerView.com/KWJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The treatment armamentarium for advanced renal cell carcinoma (RCC) has undergone rapid expansion with the validation of novel multitargeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. More recently, the emergence of dual checkpoint blockade and immunotherapy-TKI combinations in RCC has increased the number of treatment choices in the frontline setting, allowed for greater flexibility when selecting second-line agents, and sparked additional research into TKI and immune checkpoint inhibitor options in earlier disease settings. In the wake of these advances, understanding how to effectively select and sequence newer regimens through multiple lines of therapy while ensuring safe usage is crucial to maximize beneficial patient outcomes throughout the advanced RCC continuum. This unique “How I Think, How I Treat” educational on-demand activity, based on an event held adjunct to the 18th International Kidney Cancer Symposium, features personal insights from leading kidney cancer experts on how they are adapting their own practice based on the evidence supporting optimized care in advanced RCC in the context of patient-, disease-, and treatment-specific factors, as well as how the innovations fueling modern approaches to care are improving outcomes for patients with RCC. Upon completion of this activity, participants should be better able to: Assess the latest evidence and clinical implications of novel approaches, including new multitargeted tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Select optimal frontline treatment options among TKIs and combination approaches (dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors) for individual patients with advanced RCC based on relevant patient- and disease-related characteristics, including in the context of clinical trial enrollment, Apply validated targeted therapy and immunotherapy options effectively for patients with pretreated advanced RCC through multiple lines of therapy that reflect considerations of prior treatment history and patient comorbidities, Employ effective strategies to prevent and/or manage treatment-related complications with multitargeted TKIs and immune checkpoint inhibitor therapy in patients with RCC
PeerView Immunology & Transplantation CME/CNE/CPE Audio Podcast
Go online to PeerView.com/KWJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The treatment armamentarium for advanced renal cell carcinoma (RCC) has undergone rapid expansion with the validation of novel multitargeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. More recently, the emergence of dual checkpoint blockade and immunotherapy-TKI combinations in RCC has increased the number of treatment choices in the frontline setting, allowed for greater flexibility when selecting second-line agents, and sparked additional research into TKI and immune checkpoint inhibitor options in earlier disease settings. In the wake of these advances, understanding how to effectively select and sequence newer regimens through multiple lines of therapy while ensuring safe usage is crucial to maximize beneficial patient outcomes throughout the advanced RCC continuum. This unique “How I Think, How I Treat” educational on-demand activity, based on an event held adjunct to the 18th International Kidney Cancer Symposium, features personal insights from leading kidney cancer experts on how they are adapting their own practice based on the evidence supporting optimized care in advanced RCC in the context of patient-, disease-, and treatment-specific factors, as well as how the innovations fueling modern approaches to care are improving outcomes for patients with RCC. Upon completion of this activity, participants should be better able to: Assess the latest evidence and clinical implications of novel approaches, including new multitargeted tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Select optimal frontline treatment options among TKIs and combination approaches (dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors) for individual patients with advanced RCC based on relevant patient- and disease-related characteristics, including in the context of clinical trial enrollment, Apply validated targeted therapy and immunotherapy options effectively for patients with pretreated advanced RCC through multiple lines of therapy that reflect considerations of prior treatment history and patient comorbidities, Employ effective strategies to prevent and/or manage treatment-related complications with multitargeted TKIs and immune checkpoint inhibitor therapy in patients with RCC
Go online to PeerView.com/KWJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The treatment armamentarium for advanced renal cell carcinoma (RCC) has undergone rapid expansion with the validation of novel multitargeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. More recently, the emergence of dual checkpoint blockade and immunotherapy-TKI combinations in RCC has increased the number of treatment choices in the frontline setting, allowed for greater flexibility when selecting second-line agents, and sparked additional research into TKI and immune checkpoint inhibitor options in earlier disease settings. In the wake of these advances, understanding how to effectively select and sequence newer regimens through multiple lines of therapy while ensuring safe usage is crucial to maximize beneficial patient outcomes throughout the advanced RCC continuum. This unique “How I Think, How I Treat” educational on-demand activity, based on an event held adjunct to the 18th International Kidney Cancer Symposium, features personal insights from leading kidney cancer experts on how they are adapting their own practice based on the evidence supporting optimized care in advanced RCC in the context of patient-, disease-, and treatment-specific factors, as well as how the innovations fueling modern approaches to care are improving outcomes for patients with RCC. Upon completion of this activity, participants should be better able to: Assess the latest evidence and clinical implications of novel approaches, including new multitargeted tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Select optimal frontline treatment options among TKIs and combination approaches (dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors) for individual patients with advanced RCC based on relevant patient- and disease-related characteristics, including in the context of clinical trial enrollment, Apply validated targeted therapy and immunotherapy options effectively for patients with pretreated advanced RCC through multiple lines of therapy that reflect considerations of prior treatment history and patient comorbidities, Employ effective strategies to prevent and/or manage treatment-related complications with multitargeted TKIs and immune checkpoint inhibitor therapy in patients with RCC
Go online to PeerView.com/KWJ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. The treatment armamentarium for advanced renal cell carcinoma (RCC) has undergone rapid expansion with the validation of novel multitargeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor therapies. More recently, the emergence of dual checkpoint blockade and immunotherapy-TKI combinations in RCC has increased the number of treatment choices in the frontline setting, allowed for greater flexibility when selecting second-line agents, and sparked additional research into TKI and immune checkpoint inhibitor options in earlier disease settings. In the wake of these advances, understanding how to effectively select and sequence newer regimens through multiple lines of therapy while ensuring safe usage is crucial to maximize beneficial patient outcomes throughout the advanced RCC continuum. This unique “How I Think, How I Treat” educational on-demand activity, based on an event held adjunct to the 18th International Kidney Cancer Symposium, features personal insights from leading kidney cancer experts on how they are adapting their own practice based on the evidence supporting optimized care in advanced RCC in the context of patient-, disease-, and treatment-specific factors, as well as how the innovations fueling modern approaches to care are improving outcomes for patients with RCC. Upon completion of this activity, participants should be better able to: Assess the latest evidence and clinical implications of novel approaches, including new multitargeted tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors, and combination therapies in advanced renal cell carcinoma (RCC), Select optimal frontline treatment options among TKIs and combination approaches (dual checkpoint inhibition or targeted agents plus immune checkpoint inhibitors) for individual patients with advanced RCC based on relevant patient- and disease-related characteristics, including in the context of clinical trial enrollment, Apply validated targeted therapy and immunotherapy options effectively for patients with pretreated advanced RCC through multiple lines of therapy that reflect considerations of prior treatment history and patient comorbidities, Employ effective strategies to prevent and/or manage treatment-related complications with multitargeted TKIs and immune checkpoint inhibitor therapy in patients with RCC
Toni Choueiri, MD, kidney cancer specialist at Dana-Farber Cancer Institute, discusses surgical considerations and multidisciplinary care for localized kidney cancer, adjuvant therapies largely falling short of expectations, and the plethora of frontline therapies available in metastatic disease.
Dr. Toni Choueiri, do Dana-Farber Cancer Institute – USA, comenta os destaques de câncer geniturinário apresentados nos primeiros dias da ESMO 2019.
Alexi Choueiri is a neuroengineer paving the way for interfacing our minds with machines. He’s a PhD student at MIT working on developing new technologies to help us understand and repair the brain. https://linkedin.com/in/alexi-choueir... ******* Simulation interviews the greatest minds alive to inspire you to build the future ► http://simulationseries.com Design Merch, Get Paid, Spread Thought-Provoking Questions ► https://yoobe.me/simulation ******* Subscribe across platforms ► Youtube ► http://bit.ly/SimYoTu iTunes ► http://bit.ly/SimulationiTunes Instagram ► http://bit.ly/SimulationIG Twitter ► http://bit.ly/SimulationTwitter Spotify ► http://bit.ly/SpotifySim ******* Facebook ► http://bit.ly/SimulationFB Soundcloud ► http://bit.ly/SimulationSC LinkedIn ► http://bit.ly/SimulationLinkedIn Patreon ► http://bit.ly/SimulationPatreon Crypto ► http://bit.ly/SimCrypto PayPal ► https://paypal.me/simulationseries ******* Nuance-driven Telegram chat ► http://bit.ly/SimulationTG Allen's TEDx Talk ► http://bit.ly/AllenTEDx Allen's IG ► http://bit.ly/AllenIG Allen's Twitter ► http://bit.ly/AllenT ******* List of Thought-Provoking Questions ► http://simulationseries.com/the-list Get in Touch ► simulationseries@gmail.com
Dr. Toni Choueiri, diretor da Lank Center for Genitourinary Oncolgy, EUA, faz um resumo dos principais estudos em câncer renal apresentados na ASCO GU 2019, colocando em pauta, por exemplo, dados sobre inibidores de MET e inibidores de PDL-1.
Robert Figlin, MD, Steven Spielberg Family Chair in Hematology-Oncology, Cedars-Sinai Medical Center and Toni Choueiri, MD, Director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute, discuss Keytruda's approval in renal cell carcinoma (RCC).
Lenny has been fighting kidney cancer in one form or another since 2008. After doctors discovered a tumor in his kidney ten years ago, Lenny underwent several surgeries to remove tumor growths and eventually had his entire kidney removed. Unfortunately, Lenny's disease came back in 2013, and this time surgery was no longer an option. He now had an inoperable form of the disease that had spread to other parts of his body as well.Lenny started on clinical trial of a targeted drug that helped to shrink his tumor dramatically. Lenny was also feeling good and experienced minimal side effects while on the trial.When his disease returned in 2015, Lenny had additional treatment options at Dana-Farber. He started on a new form of therapy called immunotherapy. Immunotherapy harnesses the body's own immune system to recognize and destroy cancer cells, much the same way our immune system seeks out a virus or infection. Lenny's tumors have not grown since he has been on this new medication. While every day is challenge in some ways for Lenny, he maintains an upbeat and positive outlook. He calls Dr. Choueiri and his treatment team the best thing that ever happened to him.Dr. Choueiri the lead investigator of multiple national and international phase one, two and three trials in GU cancers.Dr. Choueiri is interested in developing novel therapies and biomarkers in GU malignancies, including kidney cancer. His research also focuses on epidemiology, diagnosis and treatment outcomes of GU cancers using large scale approaches such as meta-analyses from available published trials or national databases.
In 2010, Bobbi had a tumor in her kidney, and had her kidney removed. She continued to see the doctor for regular check-ups and in March 2013 she learned she had metastatic kidney cancer. She was immediately treated with immunotherapy and she has continued to respond positively to treatment. She had to start a second drug recently when her doctor discovered an enlarged lymph node. Bobbi is retired from the HR department of the Department of Corrections, she worked there for 25 years. She has been married to her husband, Buddy for 51 years. They have an adult son and daughter, and have a granddaughter who is 5. Dr. Chouieri makes her smile. She says he is straightforward and patient and always answers all her questions. She said it is easy to see why his nickname is “Dr. Wonderful.”
Dr Choueiri presents, at a press conference at ESMO 2016, results of the CABOSUN comparitive trial, which assessed outcomes of patients with metastatic rencal cell carcinoma receiving cabozantinib versus sunitnib. Both drugs are tyrosine kinase inhibitors (TKIs) targeting VEGFR, however cabozantinib has additional actions in inhibition of MET and AXL. He describes the results, which demonstrate improved progression free survival in the cabozantinib arm, and considers its progression towards wider adoption and approval.
Dr Choueiri speaks with ecancertv at ESMO 2016 to discuss results from two trials for novel therapies against metastatic renal cell carcinoma (mRCC). First, he discusses the comparative trial CABOSUN, investigating cabozantinib versus sunitinib, and then a phase 1b dose escalation of checkpoint inhibitor therapy in combination with axitinib. Considering the results of these trials, Dr Choueiri describes his hopes for the future of mRCC care.
Dr Choueiri speaks with ecancertv at ASCO 2016 about results from METEOR, a randomised phase III trial of cabozantinib for patients with advanced renal cell carcinoma (RCC), compared to everolimus. Cabozantinib displayed a significant impact on previously treated patients, improving median overall survival from 16.5 months in the everolimus arm to 21.4 months for cabozantinib, and a 33% reduction in the rate of death He also highlights the scale of the trial, from the international team gathering data to the impact on standard of care in RCC.
Dr Choueiri talks to ecancertv at the ASCO GU 2016 meeting about updates in prostate and renal cancer presented at the meeting. Dr Choueiri discusses the recent data from the subgroup analyses of METEOR and the results from the CheckMate 025 phase III trial, as well as covering some updates in renal and testicular cancer.
Dr Choueiri talks to ecancertv at the ASCO GU 2016, about a study looking at associations between analgesic use and risk of renal cell cancer overall and by subtypes, taking data from both the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). The findings support a significant positive association between non-aspirin NSAID use and risk of developing renal cell cancer, especially the lethal form.
The immune checkpoint inhibitor Opdivo (nivolumab) has been shown to increase survival for patients with metastatic clear cell kidney cancer (also called renal cell carcinoma, or RCC).
The immune checkpoint inhibitor Opdivo (nivolumab) has been shown to increase survival for patients with metastatic clear cell kidney cancer (also called renal cell carcinoma, or RCC).
The immune checkpoint inhibitor Opdivo (nivolumab) has been shown to increase survival for patients with metastatic clear cell kidney cancer (also called renal cell carcinoma, or RCC).
(Physicist, Inventor) Coming from the world of science, Edgar Choueiri is probably one of the most interesting and gifted guests I've had on the show. He is the Director of Princeton's Electric Propulsion and Plasma Dynamics Lab, Director of Princeton's Engineering of Physics Program, and Director of the Princeton 3D Audio and Applied Acoustics Lab. The results of his work is being applied in a range of products from space flight to consumer sound. Today Edgar sits down and opens up his mind to share his insight in to 3D audio, Virtual Realty, the Space Program, plasma propulsion, the uselessness of worry or conspiracy theories, creativity, and more. StudioDonovan.com