Podcasts about Nivolumab

Making strides against melanoma: how can medical oncologists and interventional oncologists join forces to deliver smarter, patient-centered care? In this episode of BackTable, Dr. Tyler Sandow, hosts Dr. Sunandana Chandra, medical oncologist at Northwestern, and Dr. Riad Salem, interventional oncologist at Northwestern to discuss the evolving management of advanced melanoma. --- This podcast is supported by an educational grant from Replimune. --- SYNPOSIS The doctors open the episode with an overview of melanoma and recent advances in its treatment, highlighting key trials such as DREAMseq and CheckMate 067. The discussion explores the shift from medical oncologist as solo primary providers to a dynamic, multidisciplinary approach to advanced cancer care—emphasizing cutting-edge treatments like immunotherapy and intratumoral oncolytic viruses. Dr. Salem shares practical insights on the procedural techniques of administering intratumoral oncolytics like Replimune, emphasizing the importance of thorough documentation and patient-centered care. The doctors also provide an overview of the ongoing IGNYTE-3 Trial, a Phase 3 study assessing the safety and efficacy of the oncolytic immunotherapy RP1 in combination with nivolumab for the treatment of advanced melanoma. The episode underscores the transformative potential of innovative melanoma treatments and the crucial role of integrated, team-based approaches in improving cancer patient outcomes. --- TIMESTAMPS 00:00 - Introduction03:48 - The Evolution of Melanoma Treatment: From Chemotherapy to Immunotherapy14:05 - The Role of Oncolytic Viruses in Melanoma Treatment20:14 - Interventional Radiology's Role in Cancer Treatment27:00 - Collaborative Approach to Cancer Care32:53 - Hyper Documentation and Communication Efficiency44:47 - Future of Intratumoral Oncolytics48:10 - Multidisciplinary Approach in Advanced Cancer Management51:46 - Conclusion and Final Thoughts --- RESOURCES DREAMseq Trial: Atkins MB, Lee SJ, Chmielowski B, et al. Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134. J Clin Oncol. 2023;41(2):186-197. doi:10.1200/JCO.22.01763 CheckMate 067 trial: Wolchok JD, Chiarion-Sileni V, Rutkowski P, et al. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. N Engl J Med. 2025;392(1):11-22. doi:10.1056/NEJMoa2407417

In today's episode, supported by Replimune, we had the pleasure of speaking with Anna C. Pavlick, BSN, MSc, DO, MBA, about the use of RP1 plus nivolumab (Opdivo) for the treatment of patients with advanced melanoma. Dr Pavlick is a professor of medicine in the Division of Hematology & Medical Oncology at Weill Cornell Medicine in New York, New York; as well as the founding director of the Cutaneous Oncology Program at Weill Cornell Medicine and NewYork-Presbyterian. In our exclusive interview, Dr Pavlick discussed the rationale for investigating this combination in patients with advanced melanoma who have received prior immune checkpoint inhibition, key efficacy and safety findings from the phase 1/2 IGNYTE trial (NCT03767348), and where the future may be headed regarding the use of oncolytic viruses in melanoma.

La Dra. María Alejandra Bravo, oncóloga médica en el centro de Tratamiento e Investigación sobre Cáncer (CTIC) en Bogotá, Colombia, junto con el Dr. Guillermo de Velasco, oncólogo médico en el Hospital Universitario 12 de Octubre en Madrid, España, presentaron recientemente en Barranquilla, Colombia, durante el congreso de CLOC, una actualización sobre el tratamiento del melanoma avanzado. Los expertos se centraron en el estudio RELATIVITY-047, que demostró la eficacia en supervivencia de la combinación de relatlimab con nivolumab, posicionándose como una valiosa opción terapéutica para estos pacientes.  Cobertura apoyada por el Curso Latinoamericano de Oncología Clínica (CLOC).  Fecha de grabación: 08 de marzo de 2025      Todos los comentarios emitidos por los participantes son a título personal y no reflejan la opinión de ScienceLink u otros. Se deberá revisar las indicaciones aprobadas en el país para cada uno de los tratamientos y medicamentos comentados. Las opiniones vertidas en este programa son responsabilidad de los participantes o entrevistados, ScienceLink las ha incluido con fines educativos. Este material está dirigido a profesionales de la salud exclusivamente. 

Welcome to another episode of the Oncology Brothers podcast! In this episode, Drs. Rahul and Rohit Gosain are joined by Dr. Toni Choueiri, a leading GU medical oncologist from Dana-Farber Cancer Institute. Together, they dive into the highlights from the GU ASCO 2025 conference, covering key studies and updates in the world of genitourinary oncology. Episode Highlights: •⁠  ⁠TALAPRO-2: An in-depth discussion on the role of PARP inhibitors in prostate cancer, focusing on the study's design, findings, and the importance of germline and NGS testing. •⁠  ⁠NIAGARA Update: Insights into the new standard of care for resectable muscle-invasive bladder cancer and the promising results from the perioperative approach with Durvalumab. •⁠  ⁠CheckMate-9ER Update: A look at the combination of Cabozantinib and Nivolumab in first-line metastatic RCC, including the latest findings and implications for treatment beyond the first line. •⁠  TiNivo2: Exploring the role of Tivozanib in the treatment landscape of RCC and potential sequencing strategies. Join us for this informative discussion that aims to keep community oncologists up to date with the latest advancements in cancer care. If you find this episode helpful, please share it with your colleagues and leave us a review! YouTube: https://youtu.be/OzeHhyAdF9Q Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠ Website: https://oncbrothers.com/ Don't forget to subscribe for more insights and updates from the Oncology Brothers!

Dr. Neeraj Agarwal and Dr. Peter Hoskin discuss key abstracts in GU cancers from the 2025 ASCO Genitourinary Cancers Symposium, including novel therapies in prostate, bladder, and kidney cancer and the impact of combination therapies on patient outcomes. TRANSCSRIPT 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-informing abstracts and other key advances in GU oncology featured at the 2025 ASCO Genitourinary Cancers Symposium. Joining me for this discussion is Dr. Peter Hoskin, the chair of this year's ASCO GU Symposium. Dr. Hoskin is a professor in clinical oncology in the University of Manchester and honorary consultant in clinical oncology at the Christie Hospital, Manchester, and University College Hospital London, in the United Kingdom. Our full disclosures are available in the transcript of this episode. Peter, thank you for joining us today. Dr. Peter Hoskin: Thank you so much, Neeraj. I am very pleased to be here. Dr. Neeraj Agarwal: The GU meeting highlighted remarkable advancements across the spectrum of GU malignancies. What stood out to you as the most exciting developments at the ASCO GU Symposium?  Dr. Peter Hoskin: The theme of this year's meeting was "Driving Innovation, Improving Patient Care," and this reflected ASCO GU's incredible milestone in GU cancer research over the years. We were thrilled to welcome almost 6,000 attendees on this occasion from over 70 countries, and most of them were attending in person and not online, although this was a hybrid meeting. Furthermore, we had more than 1,000 abstract submissions. You can imagine then that it fostered fantastic networking opportunities and facilitated valuable knowledge and idea exchanges among experts, trainees, and mentees. So, to start I'd like to come back to you for a second because the first day started with a focus on prostate cancer and some of the key clinical trials. And congratulations to you, Neeraj, on sharing the data from the TALAPRO-2 trial, which we were eagerly awaiting. I'd love to get your thoughts on the data that you presented. Could you tell us more about that trial, Abstract LBA18?  Dr. Neeraj Agarwal: Yes, Peter, 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 TALAPRO-2 trial. First of all, I would like to remind our audience that the combination of talazoparib plus enzalutamide was approved by the U.S. FDA in June 2023 in patients with metastatic castration-resistant prostate cancer harboring HRR gene alterations, after this combination improved the primary endpoint of radiographic progression-free survival compared to enzalutamide alone in the randomized, double-blind, placebo-controlled, multi-cohort phase 3 TALAPRO-2 trial. In the abstract I presented at ASCO GU 2025, we reported the final overall survival data, which was a key alpha-protected secondary endpoint in cohort 1, which enrolled an all-comer population of patients with mCRPC. So, at a median follow-up of around 53 months, in the intention-to-treat population, the combination of talazoparib plus enzalutamide significantly reduced the risk of death by 20% compared to enzalutamide alone, with a median OS of 45.8 months in the experimental arm versus 37 months in the control arm, which was an active control arm of enzalutamide. This improvement was consistent in patients with HRR alterations with a hazard ratio of 0.54 and in those with non-deficient or unknown HRR status, with a hazard ratio of 0.87. In a post hoc analysis, the hazard ratio for OS was 0.78 favoring the combination in those patients who did not have any HRR gene alteration in their tumors by both tissue and ctDNA testing. Consistent with the primary analysis, the updated rPFS data also favored the experimental arm with a median rPFS of 33.1 compared to 19.5 months in the control arm, and a hazard ratio of 0.667. No new safety signals were identified with extended follow-up. Thus, TALAPRO-2 is the first PARP inhibitor plus ARPI study to show a statistically significant and a clinically meaningful improvement in OS compared to standard-of-care enzalutamide as first-line treatment in patients with mCRPC unselected for HRR gene alterations. Dr. Peter Hoskin: Thank you, Neeraj. That's a great summary of the data presented and very important data indeed. There was another abstract also featured in the same session, Abstract 20, titled “Which patients with metastatic hormone-sensitive prostate cancer benefit more from androgen receptor pathway inhibitors? STOPCAP meta-analyses of individual participant data.” Neeraj, could you tell us more about this abstract? Dr. Neeraj Agarwal: Absolutely, I would be delighted to. So, in this meta-analysis, Dr. David Fischer and colleagues pooled individual participant data from different randomized phase 3 trials in the mHSPC setting to assess the potential ARPI effect modifiers and determine who benefits more from an ARPI plus ADT doublet. The primary outcome was OS for main effects and PFS for subgroup analyses. Prostate cancer specific survival was a sensitivity outcome. The investigators pooled data from 11 ARPI trials and more than 11,000 patients. Overall, there was a clear benefit of adding an ARPI on both OS and PFS, with hazard ratios of 0.66 and 0.51, respectively, representing a 13% and 21% absolute improvement at 5 years, respectively, with no clear difference by the class of agent. When stratifying the patients by age group, the effects of adding an ARPI on OS and PFS were slightly smaller in patients older than 75, than in those younger than 65, or aged between 65 and 75 years. Notably, in the trials assessing the use of abiraterone, we saw very little OS effects in the group of patients older than 75, however there was some benefit maintained in prostate-cancer specific survival, suggesting that other causes of death may be having an impact. The effects of the other ARPIs, or ‘lutamides' as I would call them, were similar across all three age subgroups on both OS and PFS. Therefore, the majority of patients with mHSPC benefit from the addition of ARPIs, and the benefits/risks of abiraterone and other ‘amides' must be considered in older patients.  Dr. Peter Hoskin: Thanks, Neeraj. Another great summary relevant to our day-to-day practice. Of course, there's ongoing collection of individual patient data from other key trials, which will allow robust comparison of ARPI doublet with triplet therapy (including docetaxel), guiding more personalized treatment.   Dr. Neeraj Agarwal: I agree with you, Peter, we need more data to help guide personalized treatment for patients with mHSPC and potentially guide de-escalation versus escalation strategies. Now, moving on to a different setting in prostate cancer, would you like to mention Abstract 17 titled, “Overall survival and quality of life with Lu-PSMA-617 plus enzalutamide versus enzalutamide alone in poor-risk, metastatic, castration-resistant prostate cancer in ENZA-p (ANZUP 1901),” presented by Dr. Louise Emmett? Dr. Peter Hoskin: Of course I will. So, ENZA-p was a multicenter, open-label, randomized, phase 2 trial conducted in Australia. It randomized 163 patients into adaptive doses (2 or 4 cycles) of Lu-PSMA-617 plus enzalutamide versus enzalutamide alone as first-line treatment in PSMA-PET-CT-positive, poor-risk, mCRPC. The interim analysis of ENZA-p with median follow-up 20 months showed improved PSA-progression-free survival with the addition of Lu-PSMA-617 to enzalutamide. Here, the investigators reported the secondary outcomes, overall survival, and health-related quality of life (HRQOL). After a median follow up of 34 months, overall survival was longer in the combination arm compared to the enzalutamide arm, with a median OS of 34 months compared to 26 months; with an HR of 0.55. Moreover, the combination improved both deterioration-free survival and health-related quality of life indicators for pain, fatigue, physical function, and overall health and quality of life compared to the control arm. Consistent with the primary analysis, the rPFS also favored the experimental arm with a median rPFS of 17 months compared to 14 months with a HR of 0.61. So, the addition of LuPSMA improved overall survival, and HRQOL in patients with high-risk mCRPC. Dr. Neeraj Agarwal: Thank you, Peter. Great summary, and promising results with Lu-177 and ARPI combination in first line treatment for mCRPC among patients who had two or more high risk features associated with early enzalutamide failure. Before we move on to bladder cancer, would you like to tell us about Abstract 15 titled, “World-wide oligometastatic prostate cancer (omPC) meta-analysis leveraging individual patient data (IPD) from randomized trials (WOLVERINE): An analysis from the X-MET collaboration,” presented by Dr. Chad Tang?  Dr. Peter Hoskin: Sure. So, with metastatic-directed therapy (MDT), we have a number of phase 2 studies making up the database, and the X-MET collaboration aimed to consolidate all randomized data on oligometastatic solid tumors. This abstract presented pooled individual patient data from all the published trials involving patients with oligometastatic prostate cancer who received MDT alongside standard of care (SOC) against SOC alone. The analysis included data from five trials, encompassing 472 patients with oligometastatic prostate cancer, and followed for a median of 41 months. Patients were randomly assigned in a 1:1 ratio to receive either MDT plus SOC or SOC alone. The addition of MDT significantly improved PFS. The median PFS was 32 months with MDT compared to 14.9 months with SOC alone, with an HR of 0.45. Subgroup analyses further confirmed the consistent benefits of MDT across different patient groups. Regardless of factors like castration status, receipt of prior primary treatment, stage, or number of metastases, MDT consistently improved PFS. In patients with mHSPC, MDT significantly delayed the time to castration resistance by nine months, extending it to a median of 72 months compared to 63 months in the SOC group with an HR of 0.58. In terms of OS, the addition of MDT improved the 48-month survival rate by 12%, with OS rates of 87% in the MDT+SOC group compared to 75% in the SOC alone group. Dr. Neeraj Agarwal: Thank you, Peter. These data demonstrate that adding MDT to systemic therapy significantly improves PFS, rPFS, and castration resistance-free survival, reinforcing its potential role in the treatment of oligometastatic prostate cancer. So, let's switch gears to bladder cancer and start with Abstract 658 reporting the OS analysis of the CheckMate-274 trial. Would you like to tell us about this abstract?  Dr. Peter Hoskin: Yes, sure, Neeraj. This was presented by Dr. Matt Milowsky, and it was additional efficacy outcomes, including overall survival, from the CheckMate-274 trial which evaluated adjuvant nivolumab versus placebo in patients with high-risk muscle-invasive bladder cancer after radical surgery. The phase 3 trial previously demonstrated a significant improvement in disease-free survival with nivolumab. With a median follow-up of 36.1 months, disease-free survival was longer with nivolumab compared to placebo across all patients with muscle-invasive bladder cancer, reducing the risk of disease recurrence or death by 37%. Among patients who had received prior neoadjuvant cisplatin-based chemotherapy, nivolumab reduced this risk by 42%, whilst in those who had not received chemotherapy, the risk was reduced by 31%. Overall survival also favored nivolumab over placebo, reducing the risk of death by 30% in all patients with muscle-invasive bladder cancer and by 52% in those with tumors expressing PD-L1 at 1% or higher. Among patients who had received prior neoadjuvant chemotherapy, nivolumab reduced the risk of death by 26%, whilst in those who had not received chemotherapy, the risk was reduced by 33%. Alongside this, the safety profile remained consistent with previous findings. Dr. Neeraj Agarwal: Thank you, Peter, for such a nice overview of this abstract. These results reinforce adjuvant nivolumab as a standard of care for high-risk muscle-invasive bladder cancer, offering the potential for a curative outcome for our patients. Dr. Peter Hoskin: I agree with you Neeraj. Perhaps you would like to mention Abstract 659 titled, “Additional efficacy and safety outcomes and an exploratory analysis of the impact of pathological complete response (pCR) on long-term outcomes from NIAGARA.” Dr. Neeraj Agarwal: Of course. Dr. Galsky presented additional outcomes from the phase 3 NIAGARA study, which evaluated perioperative durvalumab combined with neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer. The study previously demonstrated a significant improvement in event-free survival and overall survival with durvalumab compared to chemotherapy alone, with a manageable safety profile and no negative impact on the ability to undergo radical cystectomy. Among the 1,063 randomized patients, those who received durvalumab had a 33% reduction in the risk of developing distant metastases or death and a 31% reduction in the risk of dying from bladder cancer compared to those who received chemotherapy alone. More patients who received durvalumab achieved a pathological complete response at the time of surgery with 37% compared to 28% in the chemotherapy-alone group. Patients who achieved a pathological complete response had better event-free survival and overall survival compared to those who did not. In both groups, durvalumab provided additional survival benefits, reducing the risk of disease progression or death by 42% and the risk of death by 28% in patients with a pathological complete response, while in those patients without a pathological complete response, the risk of disease progression or death was reduced by 23% and the risk of death by 16% when durvalumab was added to the chemotherapy. Immune-mediated adverse events occurred in 21% of patients in the durvalumab group compared to 3% in the chemotherapy-alone group, with grade 3 or higher events occurring in 3% compared to 0.2%. The most common immune-related adverse events included hypothyroidism in 10% of patients treated with durvalumab compared to 1% in the chemotherapy-alone group, and hyperthyroidism in 3% versus 0.8%. At the time of the data cutoff, these adverse events had resolved in 41% of affected patients in the durvalumab group and 44% in the chemotherapy-alone group. Dr. Peter Hoskin: Thank you, Neeraj, for the great summary. These findings further support the role of perioperative durvalumab as a potential standard of care for patients with muscle-invasive bladder cancer. Dr. Neeraj Agarwal: I concur with your thoughts, Peter. Before wrapping up the bladder cancer section, would you like to mention Abstract 664 reporting updated results from the EV-302 trial, which evaluated enfortumab vedotin in combination with pembrolizumab compared to chemotherapy as first-line treatment for patients with previously untreated locally advanced or metastatic urothelial carcinoma? Dr. Peter Hoskin: Yes, of course. Dr. Tom Powles presented updated findings from the EV-302 study, and in this abstract presented 12 months of additional follow-up for EV-302 (>2 y of median follow-up) and an exploratory analysis of patients with confirmed complete response (cCR). The study had a median follow-up of 29.1 months and previously demonstrated significant improvements in progression-free survival and overall survival with enfortumab vedotin and pembrolizumab. This is now the standard of care in global treatment guidelines. Among the 886 randomized patients, enfortumab vedotin and pembrolizumab reduced the risk of disease progression or death by 52% and the risk of death by 49% compared to chemotherapy. The survival benefit was consistent regardless of cisplatin eligibility or the presence of liver metastases. The confirmed objective response rate was higher with enfortumab vedotin and pembrolizumab at 67.5% compared to 44.2% with chemotherapy. The median duration of response was 23.3 months with enfortumab vedotin and pembrolizumab compared to 7.0 months with chemotherapy. A complete response was achieved in 30.4% of patients in the enfortumab vedotin and pembrolizumab group compared to 14.5% in the chemotherapy group, with the median duration of complete response not yet reached in the enfortumab vedotin and pembrolizumab group compared to 15.2 months in the chemotherapy group. Severe treatment-related adverse events occurred in 57.3% of patients treated with enfortumab vedotin and pembrolizumab compared to 69.5% in the chemotherapy group, while in patients who achieved a complete response, severe adverse events occurred in 61.7% of those treated with enfortumab vedotin and pembrolizumab compared to 71.9% with chemotherapy. Treatment-related deaths were reported in 1.1% of patients treated with enfortumab vedotin and pembrolizumab compared to 0.9% with chemotherapy, with no treatment-related deaths occurring in those who achieved a complete response. These findings clearly confirm the durable efficacy of enfortumab vedotin and pembrolizumab, reinforcing its role as the standard of care for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma, and no new safety concerns have been identified. Dr. Neeraj Agarwal: Thank you for this great summary. Moving on to kidney cancer, let's talk about Abstract 439 titled, “Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Final follow-up results from the CheckMate-9ER trial.” Dr. Peter Hoskin: Sure. Dr. Motzer presented the final results from the phase 3 CheckMate-9ER trial, which compared the combination of cabozantinib and nivolumab against sunitinib in previously untreated advanced renal cell carcinoma. The data after more than five years follow-up show that the combination therapy provided sustained superior efficacy compared to sunitinib. In terms of overall survival, we see an 11-month improvement in median OS, 46.5 months for the cabo-nivo versus 35.5 months for sunitinib and a 42% reduction in the risk of disease progression or death, with median progression-free survival nearly doubling – that's 16.4 months in the combination group and 8.3 months with sunitinib. Importantly, the safety profile was consistent with the known safety profiles of the individual medicines, with no new safety concerns identified. Dr. Neeraj Agarwal: Great summary, Peter. These data further support the efficacy of cabo-nivo combination therapy in advanced renal cell carcinoma, which is showing a 11-month difference in overall survival. Dr. Peter Hoskin: Neeraj, before wrapping up this podcast, would you like to tell us about Abstract 618? This is titled “Prospective COTRIMS (Cologne trial of retroperitoneal lymphadenectomy in metastatic seminoma) trial: Final results.” Dr. Neeraj Agarwal: Sure, Peter. I would be delighted to. Dr Heidenrich from the University of Cologne in Germany presented the COTRIMS data evaluating retroperitoneal LN dissection in patients with clinical stage 2A/B seminomas. Seminomas are classified as 2A or B when the disease spreads to the retroperitoneal lymph nodes of up to 2 cm (CS IIA) or of more than 2 cm to up to 5 cm (CS 2B) in maximum diameter, respectively. They account for 10-15% of seminomas and they are usually treated with radiation and chemotherapy. However, radiation and chemo can be associated with long-term toxicities such as cardiovascular toxicities, diabetes, solid cancers, leukemia, particularly for younger patients. From this standpoint, Dr Heidenrich and colleagues evaluated unilateral, modified template, nerve-sparing retroperitoneal lymph node dissection as a less toxic alternative compared to chemo and radiation. They included 34 patients with negative AFP, beta-HCG, and clinical stage 2A/B seminomas. At a median follow-up of 43.2 months, the trial demonstrated great outcomes: a 99.3% treatment-free survival rate and 100% overall survival, with only four relapses. Antegrade ejaculation was preserved in 88% of patients, and severe complications such as grade 3 and 4 were observed in 12% of patients. Pathological analysis revealed metastatic seminoma in 85% of cases, with miR371 being true positive in 23 out of 24 cases and true negative in 100% of cases. It appears to be a valid biomarker for predicting the presence of lymph node metastases. These findings highlight retroperitoneal lymph node dissection is feasible; it has low morbidity, and excellent oncologic outcomes, avoiding overtreatment in 80% of patients and sparing unnecessary chemotherapy or radiotherapy in 10-15% of cases. Dr. Peter Hoskin: Great summary and important data on retroperitoneal lymphadenectomy in metastatic seminoma. These findings will help shape clinical practice. Any final remarks before we conclude today's podcast? Dr. Neeraj Agarwal: Before wrapping up this podcast, I would like to say that we have reviewed several abstracts addressing prostate, bladder, kidney cancers, and seminoma, which are impacting our medical practices now and in the near future. Peter, thank you for sharing your insights with us today. These updates are undoubtedly exciting for the entire GU oncology community, and we greatly appreciate your valuable contribution to the discussion and your leadership of the conference. Many thanks. Dr. Peter Hoskin: Thank you, Neeraj. Thank you for the opportunity to share this information more widely. I'm aware that whilst we have nearly 6,000 delegates, there are many other tens of thousands of colleagues around the world who need to have access to this information. And it was a great privilege to chair this ASCO GU25. So, thank you once again, Neeraj, for this opportunity to share more of this information that we discussed over those few days. Dr. Neeraj Agarwal: Thank you, Peter. 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. 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. 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. Peter Hoskin Follow ASCO on social media:      @ASCO on Twitter      ASCO on Bluesky  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. Peter Hoskin: Research Funding (Institution): Varian Medical Systems, Astellas Pharma, Bayer, Roche, Pfizer, Elekta, Bristol Myers  

Según estudio: Combinar 2 fármacos ayuda a prolongar la vida de los pacientes con melanoma metastásico.Para hablar de ello nos acompañó el Dr. Jerónimo Rodríguez Cid, Oncólogo, Jefe de Oncología del Instituto Nacional de Enfermedades de Ciudad de México.La combinación de dos fármacos de inmunoterapia puede ser un tratamiento para los enfermos con melanoma metastásico avanzado, un cáncer agresivo y mortal, cuando es resistente a la terapia estándar actual, según un estudio que publicó, Nature Medicine.En los ensayos clínicos, los investigadores descubrieron que la terapia combinada puede extender la cantidad de tiempo que los pacientes viven sin que el cáncer empeore (supervivencia libre de progresión) y ayuda a superar la resistencia a las inmunoterapias anteriores, lo que permite que más personas se beneficien del tratamiento.El enfoque combinado de ambos fármacos “debería ser el régimen farmacológico preferido para las personas con cáncer que no han respondido a un tratamiento previo de inmunoterapia”, se comentó en un comunicado de la UCLA.El estudio, en el que participaron 91 personas, combinó los medicamentos de inmunoterapia Ipilimumab y Nivolumab.

Welcome to the Oncology Brothers Podcast! In this episode, Drs. Rohit and Rahul Gosain are joined by Dr. Saby George from Roswell Park Comprehensive Cancer Center to discuss the recent approval of subcutaneous nivolumab based on the CheckMate-67T study. Join us as we delve into: •⁠  ⁠The study design and findings of CheckMate-67T •⁠  ⁠The implications of subcutaneous nivolumab for patients and healthcare providers •⁠  ⁠Safety signals and side effects associated with the new formulation •⁠  ⁠The significant time savings for patients receiving treatment •⁠  ⁠Real-world experiences from patients involved in the trial This episode highlights how the subcutaneous formulation of nivolumab can enhance patient care by reducing time spent in infusion centers while maintaining efficacy and safety. Tune in to learn more about this exciting advancement in cancer treatment and its potential impact on patient quality of life! Don't forget to like, subscribe, and check out our other episodes for more insights on FDA drug approvals, conference highlights, and treatment algorithms. We are the Oncology Brothers! YouTube: https://youtu.be/4blP8jqizUQ Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers Subscribe to our channel for more insights on oncology treatments and patient care!

Interview with Michael A. Postow, MD, author of Intracranial Outcomes of Ipilimumab and Nivolumab in Melanoma Brain Metastases After Progression on Anti–PD-1 Therapy. Hosted by Vivek Subbiah, MD. Related Content: Intracranial Outcomes of Ipilimumab and Nivolumab in Melanoma Brain Metastases After Progression on Anti–PD-1 Therapy

Interview with Michael A. Postow, MD, author of Intracranial Outcomes of Ipilimumab and Nivolumab in Melanoma Brain Metastases After Progression on Anti–PD-1 Therapy. Hosted by Vivek Subbiah, MD. Related Content: Intracranial Outcomes of Ipilimumab and Nivolumab in Melanoma Brain Metastases After Progression on Anti–PD-1 Therapy

In today's episode, supported by Bristol Myers Squibb, we had the pleasure of speaking with Roxana S. Dronca, MD, about the FDA approval of subcutaneous nivolumab and hyaluronidase-nvhy (Opdivo Qvantig; subcutaneous nivolumab) for advanced or metastatic solid tumors. Dr Dronca is a professor of oncology, a consultant in the Division of Hematology/Oncology in the Department of Internal Medicine, and director of the Mayo Clinic Comprehensive Cancer Center in Jacksonville, Florida. On December 27, 2024, the FDA approved subcutaneous nivolumab across approved adult, solid tumor nivolumab indications, including as monotherapy, monotherapy maintenance after completion of nivolumab in combination with ipilimumab (Yervoy), or in combination with cabozantinib (Cabometyx) or chemotherapy. This regulatory decision was backed by findings from the phase 3 CheckMate-67T trial (NCT04810078) and includes indications for melanoma, renal cell carcinoma, non–small cell lung cancer, urothelial carcinoma, head and neck squamous cell carcinoma, colorectal cancer, esophageal carcinoma, esophageal adenocarcinoma, hepatocellular carcinoma, gastric cancer, and gastroesophageal junction cancer. In our exclusive interview, Dr Dronca discussed the significance of this FDA approval across multiple solid tumor indications, pivotal findings from the CheckMate-67T trial, and how this approval represents a paradigm shift in modern cancer care delivery.

In this week's episode we'll learn more about an experimental regimen for classical Hodgkin lymphoma that combines brentuximab vedotin, nivolumab, and chemotherapy; a possible role for type 1 interferon signaling in developing autoantibodies to red blood cells in sickle cell disease; and how genomic alterations affecting class I human leukocyte antigen molecules may affect patients with cutaneous T-cell lymphoma. Featured Articles:Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced-stage classical Hodgkin lymphomaIFN-I promotes T-cell–independent immunity and RBC autoantibodies via modulation of B-1 cell subsets in murine SCDGenetic alteration of class I HLA in cutaneous T-cell lymphoma

In this episode, Alexa Basilio, PharmD, BCOP and Jessica Davis, PharmD, BCOP, CPP discuss immune-related adverse events and toxicities among patients using immune checkpoint inhibitors. This overview will include discussion about: How and when to monitor and treat mild vs severe immune-related toxicitiesThe art of balancing and tapering low-dose and high-dose corticosteroidsDifferentiating between immune-related and chemotherapy- or targeted therapy–associated adverse events for optimal management approachesInvolvement of multidisciplinary teams early during treatment to prevent immune-related adverse eventsImportance of educating patients, caregivers, and providers on immune-related toxicitiesPresenters: Alexa Basilio, PharmD, BCOPUniversity of Florida College of Pharmacy Oncology Pharmacy Specialist McKesson, The US Oncology NetworkTampa, Florida Jessica Davis, PharmD, BCOP, CPP Levine Cancer InstituteClinical Pharmacist Coordinator, Adult Hematology/OncologyAtrium Health Levine CenterCharlotte, North Carolina Link to full program: https://bit.ly/3We4HJy

In today's episode, we had the pleasure of speaking with Alex F. Herrera, MD, about key safety and efficacy findings from the phase 3 SWOG S1826 trial (NCT03907488) evaluating nivolumab (Opdivo) plus doxorubicin, vinblastine, and dacarbazine (N+AVD) vs brentuximab vedotin (BV) plus AVD (BV+AVD) in adolescent and adult patients with stage III or IV advanced-stage classic Hodgkin lymphoma. Herrera is chief of the Division of Lymphoma in the Department of Hematology & Hematopoietic Cell Transplantation, as well as the associate medical director of the Briskin Center for Clinical Research and an associate professor in the Division of Lymphoma in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope in Duarte, California. After 2.1 years of follow-up (range, 0-4.2), N+AVD prolonged median progression-free survival (PFS) and had a more tolerable safety profile compared with BV+AVD. The 2-year PFS rate with N+AVD was 92% (95% CI, 89%-94%) vs 83% (95% CI, 79%-86%) with BV+AVD (HR, 0.45; 95% CI, 0.30-0.65). Notably, the benefit with N+AVD was consistent across diverse patient subgroups enrolled in the study. In our exclusive interview, Dr Herrera expanded on the rationale for conducting SWOG S1826, detailed key data showing sustained benefit and safety with N+AVD, and explained how these results support the use of N+AVD as a strong candidate for primary treatment in adolescent and adult patients with stage III or IV Hodgkin lymphoma.

In this JCO Article Insights episode, Rohit Singh provides a summary on "First-Line Nivolumab Plus Relatlimab Versus Nivolumab Plus Ipilimumab in Advanced Melanoma: An Indirect Treatment Comparison Using RELATIVITY-047 and CheckMate 067 Trial Data", by Long et al, published in the November issue of the Journal of Clinical Oncology. The article provides insights into the use of the two dual immune checkpoint inhibitor regimens in patients with untreated advanced melanoma. TRANSCRIPT Rohit Singh: Hello and welcome to JCO Article Insights. I'm your host Rohit Singh, Assistant Professor at the University of Vermont Cancer Center and today we'll be discussing the article “First-Line Nivolumab Plus Relatlimab Versus Nivolumab Plus Ipilimumab in Advanced Melanoma: An Indirect Treatment Comparison Using RELATIVITY-047 and CheckMate 067 Trials,” authored by Dr. Georgina Long from the Melanoma Institute of Australia and her colleagues.  So as we know, nivolumab plus relatlimab and nivo plus ipi, I'm going to refer to as ipi-nivo moving forward, are dual immune checkpoint inhibitors regimens that are approved for treating patients with advanced melanoma based on the phase 2 and 3 RELATIVITY-047 and phase 3 CheckMate 067 trials respectively. Nivo plus relatlimab is the only dual PD-1 and LAG-3 inhibitor regimen approved for treating patients with advanced melanoma and relatlimab is the first in class human IgG4 LAG-3 blocking antibody. Ipi plus nivo is a dual PD-1 and CTLA-4 inhibitor regimen.  So this paper basically is an indirect treatment comparison using a patient level database from these trials and this pretty much was conducted because of the absence of head to head trials looking at different regimens in advanced melanoma in first line setting. In this trial, the authors tried to compare these two trials. However, it's always hard to compare two different trials and we usually don't do cross trial comparisons. The problem is that the groups might be different to begin with. For example, one group might have younger patients, healthier patients, while the other might have older or sicker. These differences can make it hard to tell if the treatment caused improvement or if the groups were different to begin with. In this trial, researchers use inverse probability of treatment weighting to adjust the baseline differences between the two patient groups or between these two trials. Inverse probability of treatment weighting is a method used in research to help make a fair comparison between two groups when studying how a treatment intervention works. Basically, IPTW helps level the playing field between the two groups or like two trials for this paper. So, it calculates the likelihood of receiving a treatment. For each person, for each patient, researchers estimate the chance they would have gotten the treatment based on their characteristics like age, health, condition, their baseline staging, and based on that they create weights. People who are less likely to get the treatment but did are given more weight, and those who are very likely to get the treatment are given less weight. The same is done for the group that didn't get the treatment, and then they rebalance the groups. By applying these weights the group becomes more similar in their characteristics as if everyone had an equal chance of getting the treatment. This way, IPTW helps researchers focus on the effect of treatment itself and other differences between the groups. It's like adjusting the scales to make sure you are comparing apples to apples.  The key outcomes the authors are looking at in this one was progression free survivals, overall survival, confirmed objective response rate, melanoma specific survival, and treatment related adverse events. Looking at the results of this cross comparison trial, first looking at the PFS or progression free survival, both regimens ipi plus nivo and nivo plus relatlimab, showed similar PFS. At 36 months, PFS was 36% in nivo-relatlimab versus 39% in the ipi-nivo regimen with a hazard ratio of 1.08 indicating no significant differences. Looking at the overall survival at 36 months, overall survival was 57% in both the treatment regimens with a hazard ratio of 0.14, again, indicating no significant differences. Now looking at another confirmed objective response rate, confirmed objective rates were similar between both treatment regimens after weighting, 48% versus 50% with an odds ratio of 0.91 suggesting comparable response rates between the two regimens. Looking at melanoma specific survival at 36 months it was 65% versus 62%. Both treatments had similar melanoma specific survival with a hazard ratio 0.86.  An interesting thing in these results was subgroup analysis. Subgroups showed larger numerical differences in efficacy which favored ipi-nivo over nivo-relatlimab that included acral melanoma with a hazard ratio of 1.42 and OS with a hazard ratio of 1.72 in favor of ipi-nivo. Similarly for BRAF mutant melanoma, it showed a confirmed objective response rate with odds ratio 1.54 and same applied to mucosal melanoma with odds ratio of 1.59 and patients who have high LDH more than two times upper level limit. Looking at the safety and adverse side effects, nivolumab plus relatlimab had fewer grade 3 or 4 treatment related adverse effect which is 23% versus 61% and fewer any grade treatment related adverse events leading to discontinuation which was 17% versus 41%, which means 41% of the patients in the ipi-nivo arm lead to discontinuation. However, I would like to add to that that ipi-nivo was conducted much earlier and at that time we were still kind of assessing and trying to understand the immunity adverse effects, how to manage them, which probably could have made discontinuation more common compared to a nivo-relatlimab trial. By that time we definitely had much more experience dealing with immunity adverse effects.A couple of things mentionable in this, notable rates of hepatic and GI grade 3 or 4 treatment adverse events were lower in nivo plus relatlimab than with ipi-nivo, although the onset of any grade endocrine GI hepatic or skin related treatment related adverse events occurred most frequently in both treatment arms and in less than three months from randomization.  So looking at all this data and looking at all this, it definitely seems like both the trials are very comparable in terms of efficacy, though nivo plus relatlimab seems to have a better safety profile. This trial does have some strengths. It does use the patient level data from two large well conducted trials allowing for a robust comparison and inverse weighting which would definitely better help balance baseline characteristics, enhancing the reliability of the results, and it does lead to comprehensive assessment of both efficacy and safety outcomes, and provides a holistic view of the treatments. Given all this, definitely the fact that it's a cross comparison trial which leads to a big limitation, as I already mentioned, like definitely two trials, it's hard to compare two trials which can have its own inherited biases. So it has some differences in trial design, conduct and follow up times. Small size subgroup analysis definitely limits the ability to draw definite conclusions from those groups. There's definitely some inherent uncertainty with direct head to head cross comparison trials.  Looking at the future direction I would take from this trial, if we can have a direct head to head trial because both of the treatments are proven first line setting, it will be comparing these two regimen that can definitely provide more definite evidence and further research is needed to explore the efficacy of these regimens in specific subgroups. As I mentioned in this, some subgroups showed increased benefit in the ipi-nivo regimen, however, they were very small sample size so we need more research exploring those subgroups. One other part in both these trials, patients with active brain mets were excluded. However, there's a phase 2 trial looking at ipi-nivo in active brain mets patients. So I think assessing patients with active brain mets moving forward is also a crucial part looking at, because often, patients with advanced melanoma develop brain mets. It does lead to some unanswered questions like long term survival and quality of life. How do these regimens compare in terms of long term survival and quality of life? While the study provides data on PFS and OS, long term survival and quality of life metrics are essential for understanding the full impact of these treatments. Optimal sequencing strategies: what are the optimal sequence strategies for these patients who progress on one regimen? There is data suggesting that patients may respond to alternative regimens after progression, but more research is needed to establish the best treatment sequence. And real world performance: how do these treatments perform in real world settings outside of clinical trials? Real world data can provide insight into the effectiveness and safety of these regimens in a broader patient population.  So, in summary, nivo plus relatlimab offers similar efficacy to nivolumab plus ipilimumab but a significantly improved safety profile, making it the potentially preferable option for patients with untreated advanced melanoma. However, results should be interpreted with caution due to limitations of cross trial analysis for certain subgroups like acral melanoma, mucosal melanoma, BRAF mutant melanoma, and patients with high LDH more than two times off upper normal limit. The trial showed that there's a trend definitely with ipi-nivo may be more beneficial. Also, today data on the use of nivolumab plus relatlimab in active brain mets has not been reported. Based on these existing data, ipi-nivo remains a standard immunotherapy for patients with active brain mets. Further research, including direct head to head trials is needed to confirm these findings and explore optimal treatment strategies.  Thank you for tuning into today's episode. We hope this detailed summary of the study comparing Nivolumab Plus Relatlimab and Nivolumab Plus Ipilimumab in advanced melanoma has been informative. This is Rohit Singh. Thank you again for listening to JCO Article Insights. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/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. 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.  

In this episode, Bernie and Anthony are joined by two special guest expert hematologists: Dr. David Russler-Germain Dr. Tycel Phillips We discuss recent updates in the treatment of upfront Classical Hodgkin Lymphoma, including whether the SWOG S1826 and HD21 trials change practice! Will it be a landslide victory for nivolumab? Is brentuximab fired? Stay tuned to find out!

In this episode, listen to Ana Oaknin, MD, PhD and Alexandra Leary, MD, PhD, share their clinical insights and takeaways on key updates and new data presented for ovarian, endometrial, and cervical cancer at the ESMO 2024 annual congress including:Phase III PRIMA/ENGOT-OV26/GOG-3012 Final OS Results: Niraparib as First-Line Maintenance in Advanced Ovarian CancerATHENA COMBO/GOG-3020/ENGOT-ov45: Rucaparib With or Without Nivolumab Maintenance in Newly Diagnosed Ovarian CancerPhase II PICCOLO Trial of Mirvetuximab Soravtansine in Recurrent Platinum-Sensitive Ovarian Cancer With High-FRα ExpressionPhase III KEYNOTE-B21/GOG-3053 Study of Adjuvant Chemotherapy With or Without Radiotherapy With or Without Pembrolizumab in Patients With Newly Diagnosed Endometrial Cancer or Carcinosarcoma After Curative Surgery With no Residual DiseasePhase III KEYNOTE-A18 Overall Survival Results: Pembrolizumab Plus Concurrent Chemoradiation in High-Risk Locally Advanced Cervical Cancer Program faculty:Ana Oaknin, MD, PhDHead of Gynaecologic Cancer ProgrammeDepartment of Medical OncologyVall d' Hebron University HospitalVall d'Hebron Institute of Oncology Barcelona, SpainAlexandra Leary, MD, PhDCo-Director, Department of Medical OncologyMedical Oncologist, GynecologyTeam Leader, Gynecologic Translational Research Lab, Institut Gustave RoussyParis, FranceResources:To download the slides associated with this podcast discussion, please visit the program page.

Did you miss the ESMO Congress 2024? Listen here: NEJM Editor-in-Chief Eric Rubin and NEJM Evidence Associate Editor Oladapo Yeku discuss research that was presented at the 2024 European Society of Medical Oncology annual meeting. Visit NEJM.org to read the latest research.

In deze podcast bespreekt prof. dr. ir. Koos van der Hoeven met dr. Daphne Dumoulin en dr. Robin Cornelissen (beiden Erasmus MC, Rotterdam) de vierjaarsupdate van de CheckMate 9LA-studie. In deze studie zijn patiënten met stadium IV niet-kleincellig longcarcinoom in eerste behandellijn gerandomiseerd naar de combinatie nivolumab en ipilimumab plus twee kuren platinabevattende chemotherapie of naar vier kuren chemotherapie. Aan bod komen onder andere de vierjaarsresultaten en zij vertalen deze naar de Nederlandse praktijk. Referenties 1. SmPC Opdivo (nivolumab). Te raadplegen via https://www.ema.europa.eu/nl/documents/product-information/opdivo-epar-product-information_nl.pdf 2. SmPC Yervoy (ipilimumab). Te raadplegen via https://www.ema.europa.eu/en/documents/product-information/yervoy-epar-product-information_en.pdf 3. VPI Opdivo en Yervoy. Te raadplegen via https://www.hcp-portal.nl/deeplink/677bd91e-af91-4fc7-9ca1-894637f7ab01 4. Carbone DP, et al. J Immunother Cancer 2024;12:e008189. 5. Richtlijn Niet-kleincellig longcarcinoom. Te raadplegen via https://richtlijnendatabase.nl/richtlijn/niet_kleincellig_longcarcinoom/startpagina_-_niet-kleincellig_longcarcinoom.html 6. Advies Commissie BOM. Nivolumab en ipilimumab gecombineerd met 2 cycli chemotherapie als eerstelijnsbehandeling voor gemetastaseerd niet-kleincellig longcarcinoom. Medische Oncologie; oktober 2021. 7. Van den Heuvel MM, et al. Plaatsbepaling nivolumab, ipilimumab en chemotherapie in de eerstelijnsbehandeling van mNSCLC. Pulmoscript; december 2021. Disclosures Dr. Daphne Doumoulin: honoraria: AstraZeneca, Bristol-Myers Squibb, MSD, Novartis, Pfizer en Roche; advisory boards: Amgen, Bristol-Myers Squibb en MSD Dr. Robin Cornelissen: advisory boards: BMS, Johnson&Johnson, MSD, Pierre Fabre Medicament en Spectrum; speakers fee: BMS en Pfizer. Prof. dr. ir. Koos van der Hoeven: Astellas, Bayer, BMS, Daiichi Sankyo, Gilead, Novartis, Pfizer, Seagen, voorzitter Oncomid, lid Adviescollege VIG en lid RVT DICA. 7356-NL-2400046

Drs Park and Sonpavde discuss the CheckMate901 trial, which showed survival improvements with nivolumab plus chemotherapy in metastatic urothelial cancer.

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss promising combination therapies and other compelling advances in genitourinary cancers in advance of the 2024 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I'm the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I'm delighted to be joined by Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical program director of genitourinary cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing some key abstracts in GU oncology that will be featured at the 2024 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode. Jeanny, it's great to have you on the podcast. Dr. Jeanny Aragon-Ching: Thank you so much, Dr. Agarwal. It's a pleasure to be here. Dr. Neeraj Agarwal: So, Jeanny, let's start with some bladder cancer abstracts. Could you tell us about the Abstract 4509 titled, “Characterization of Complete Responders to Nivolumab plus Gemcitabine Cisplatin versus Gemcitabine Cisplatin Alone in Patients with Lymph Node Only Metastatic Urothelial Carcinoma from the CheckMate 901 Trial.”  Dr. Jeanny Aragon-Ching: Of course, Neeraj, I would be delighted to. First, I would like to remind our listeners that the CheckMate 901 trial was a randomized, open-label, phase 3 study, in which this particular sub-study looked at cisplatin-eligible patients with previously untreated, unresectable, or metastatic urothelial carcinoma who were assigned to receive the combination of gemcitabine and cisplatin, followed by up to 2 years of nivolumab or placebo. Based on the data presented at ESMO 2023 and subsequently published in the New England Journal of Medicine, which shows significantly improved progression-free survival and overall survival in patients receiving the combination of gemcitabine, cisplatin, and nivolumab, this regimen was approved in March 2024 as a first-line therapy for patients with unresectable or metastatic urothelial carcinoma.  In the abstract that will be featured at ASCO this year, Dr. Matt Galsky and colleagues present a post-hoc analysis that aims to characterize a subset of patients with complete response as well as those with lymph node-only metastatic disease. In patients receiving the experimental treatment, 21.7% achieved a complete response, while 11.8% of the patients in the control arm achieved a complete response.  Among these complete responders, around 52% had lymph- node-only disease in both arms. Furthermore, when characterizing the subgroup of patients with lymph-node-only disease, those receiving the combination of gemcitabine-cisplatin plus nivolumab had a 62% reduction in the risk of progression or death and a 42% reduction in the risk of death compared to those treated with gemcitabine-cisplatin alone.  The median overall survival in the experimental arm in this subgroup was around 46.3 months, while it was only 24.9 months in the control arm. The ORR in patients with lymph-node-only disease receiving gem-cis plus nivo was about 81.5% compared to 64.3% in those treated with gem-cis alone. Dr. Neeraj Agarwal: Thank you, Jeanny, for the excellent summary of this abstract. We can say that nivolumab plus gemcitabine-cisplatin induced durable disease control and clinically meaningful improvements in OS and PFS compared to gem-cis alone in patients with lymph- node-only metastasis, and deserves to be considered as one of the options for these patients.  In a similar first-line metastatic urothelial carcinoma setting, Abstract 4502, also reported data on a recently approved combination of enfortumab vedotin and pembrolizumab. Can you tell us more about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Sure, Neeraj. So, as quick reminder to our audience, this regimen was tested in the EV-302 phase 3 trial, where patients with previously untreated, locally advanced or metastatic urothelial carcinoma were randomized to receive enfortumab vedotin, plus pembrolizumab or gemcitabine plus either cisplatin or carboplatin. These data were also first presented at ESMO 2023 and subsequently published in the New England Journal of Medicine. They showed that this immune based combination significantly improved both progression free survival and overall survival, which were the primary endpoints compared to chemotherapy. In this abstract, Dr. Shilpa Gupta from the Cleveland Clinic and colleagues present the results of patient reported outcomes based on quality-of-life questionnaires in this trial.  Time to pain progression and time to confirm deterioration were numerically longer in patients treated with EV plus pembro, and patients with moderate to severe pain at baseline receiving this combination had a meaningful improvement in the Brief Pain Inventory Short-Form worst pain from week 3 through 26. Dr. Neeraj Agarwal: Thank you, Jeanny. This means that patients treated with EV plus pembro did not only have improved survival compared with platinum-based chemotherapy, but also improvement in their quality-of-life and functioning, further supporting the value of this combination for patients with locally advanced or metastatic urothelial carcinoma. This is terrific news for all of our patients.   Before we wrap up the bladder cancer section, would you like to tell our listeners about Abstract 4565, which provides the data on the efficacy of trastuzumab deruxtecan in patients with bladder cancer? Dr. Jeanny Aragon-Ching: Yes, Neeraj; this is timely given the recent FDA approval, which we will talk about. The abstract is titled, “Efficacy and Safety of Trastuzumab Deruxtecan in Patients with HER2 Expressing Solid Tumors: Results from the Bladder Cohort of the DESTINY-PanTumor02 Study.” And as a quick reminder, the DESTINY-PanTumor02 was a phase 2 open-label study where trastuzumab deruxtecan, an antibody-drug conjugate targeting HER2 expression on cancer cells, was evaluated in patients with HER2-expressing locally advanced or metastatic disease who previously received systemic treatment or who had no other treatment options. The expression of HER2 was evaluated on immunohistochemistry by local or central testing.   The primary endpoint was confirmed objective response rate by investigator assessment. Secondary endpoints included duration of response, progression free survival, disease control rate, and safety. The primary analysis, which was published in the Journal of Clinical Oncology, showed an ORR of 37.1% and responses across all cohorts and the median duration of response was 11.3 months. Based on these results, fam-trastuzumab deruxtecan-nxki was just granted accelerated FDA approval for unresectable or metastatic HER2-positive solid tumors in April 2024.  So, back to this abstract; Dr. Wysocki and colleagues report the results of the bladder cancer cohort. This study included 41 patients with urothelial cancer and at a median follow up of around 12.6 months, the objective response rate among these patients was 39%, the median PFS was 7 months, and the duration of response median was 8.7 months. The disease control rate at 12 weeks was around 71%. Regarding the safety profile, 41.5% of patients experienced grade ≥3 drug related adverse events and interstitial lung disease or pneumonitis did occur in about 4 patients. Although there was no statistical comparison between different groups, the ORR was numerically highest among the HER2 3+ group with 56.3%.  Dr. Neeraj Agarwal: Thank you, Jeanny. So, these data support consideration of trastuzumab deruxtecan as a salvage therapy option for pre-treated patients with HER2 expressing urothelial cancers and show that we are extending our treatment options to include therapies with novel mechanisms of action. This is definitely exciting news for patients with bladder cancer. Dr. Jeanny Aragon-Ching: Yes, absolutely, Neeraj. Now, let's switch gears a bit to prostate cancer. Could you tell us about Abstract 5005 which is titled, “EMBARK Post Hoc Analysis of Impact of Treatment Suspension on Health Quality-of-Life?” Dr. Neeraj Agarwal: Of course, I'd be happy to. So, enzalutamide was recently granted FDA approval for the treatment of patients with non-metastatic castration-sensitive prostate cancer with biochemical recurrence at high-risk of metastasis, based on the results of the EMBARK trial, which was a phase 3 study where patients with high-risk biochemical recurrence were randomized to receive either enzalutamide with leuprolide, enzalutamide monotherapy, or placebo plus leuprolide. The primary endpoint was metastasis-free survival with secondary endpoints including overall survival and safety.  Results showed that patients receiving enzalutamide alone or enzalutamide plus leuprolide had significantly improved metastasis-free survival compared to those treated with leuprolide alone while preserving health-related quality-of-life.   One important aspect in the design of the trial was that patients who achieved undetectable PSA at week 37 underwent treatment suspension. The treatment was resumed if PSA rose to more than 2 ng/ml for patients who underwent radical proctectomy or when PSA rose to more than 5 ng/ml for those who did not undergo surgery.  In this abstract, Dr. Stephen Freedland and colleagues present a post-hoc analysis of health-related quality-of-life outcomes after treatment suspension between weeks 37 and 205. They found that treatment was suspended in 90.9% of patients receiving enzalutamide plus leuprolide, 85.9% of those receiving enzalutamide monotherapy, and 67.8% of those receiving leuprolide monotherapy. Among those patients who stayed on treatment suspension, a trend toward numerical improvement in health-related quality-of-life after week 37 was seen in all 3 arms and this reached clinically meaningful threshold at week 205 in pain questionnaires, physical well-being, urinary and bowel symptoms. For hormonal treatment side effects, all arms reached clinically meaningful improvement at the subsequent assessments of week 49 to week 97. However, patients slowly deteriorated, with clinically meaningful deterioration at week 205 relative to week 37 in patients receiving the combination of enzalutamide and leuprolide and those treated with leuprolide.    Concerning sexual activity, a clinically meaningful improvement was reported only in patients receiving enzalutamide plus leuprolide, possibly because sexual function was better preserved prior to suspension in the enzalutamide monotherapy arm and thus there was less opportunity for “improvement” while on suspension.  Dr. Jeanny Aragon-Ching: Thank you, Neeraj, for this great summary. This analysis confirms that treatment suspension in good responders might lead to a clinically meaningful improvements in health-related quality-of-life.   Now, moving on to patients with metastatic castration-resistant prostate cancer, what can you tell us, about Abstract 5008 titled, “Baseline ctDNA analyses and associations with outcomes in taxane-naive patients with mCRPC treated with 177Lu-PSMA-617 versus change of ARPI in PSMAfore”?  Dr. Neeraj Agarwal: Sure, Jeanny. The PSMAfore trial was a phase 3 study that compared the efficacy of 177Lu-PSMA-617 versus an ARPI switch in patients with mCRPC and prior progression on a first ARPI, and not previously exposed to docetaxel chemotherapy. The primary endpoint was rPFS and OS was an important secondary endpoint. The primary analysis presented at ESMO 2023 showed a significantly prolonged rPFS in patients receiving lutetium. In the abstract that will be featured at the 2024 ASCO Annual Meeting, Dr. Johann De Bono and colleagues present an exploratory analysis regarding the associations between baseline circulating tumor DNA and outcomes.  ctDNA fraction was evaluated in all samples as well as alterations in key prostate cancer drivers prevalent in more than 10% of participants.  The investigators sought to interrogate the association of ctDNA fraction or alterations with rPFS, PSA response, and RECIST response at data cutoff. They showed that median rPFS was significantly shorter in patients with a ctDNA fraction >1% compared to those with a fraction < 1% regardless of the treatment arm. Furthermore, ctDNA fraction >1% was also associated with worst RECIST response and PSA50 response. Regarding prostate cancer drivers, median rPFS was significantly shorter in patients with alterations in the AR, TP53 or PTEN in both treatment arms. There was no significant association between ctDNA alterations and PSA or objective responses. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So, these results show that the presence of a ctDNA fraction >1% or alterations in AR, P53 and PTEN were all associated with worse outcomes regardless of treatment with lutetium or change in the ARPI. These data are definitely important for counseling and prognostication of patients in the clinic and may guide the design of future clinical trials. Let's move on to kidney cancer. Neeraj, do you have any updates for us?  Dr. Neeraj Agarwal:  Sure. In Abstract 4512 titled, “A Multi-institution Analysis of Outcomes with First-Line Therapy for 99 Patients with Metastatic Chromophobe Renal Cell Carcinoma,” Dr. Sahil Doshi and colleagues present a retrospective, multi-institutional study comparing survival outcomes, including time-to-treatment failure and overall survival, between different first-line treatment options in patients with metastatic chromophobe renal cell carcinoma, where limited clinical trial data exists to guide systemic therapy. They categorized patients into 4 treatment groups: and immune checkpoint inhibitors + targeted therapy doublets (such as ICI VEGF TKI); pure immune checkpoint inhibitor monotherapy and doublets (such as ipilimumab plus nivolumab); targeted therapy doublets (such as lenvatinib plus everolimus), and targeted monotherapy (such as sunitinib).  They identified 99 patients, of whom 54 patients received targeted monotherapy, 17 received ICI VEGF-TKI, 14 received targeted doublet, and 14 patients received only ICI therapies. So the patients treated with any doublet containing a targeted agent had a 52% decrease in the risk of treatment failure and a 44% decrease in the risk of death compared to those treated with targeted monotherapy. The median time to treatment failure was 15 months with IO-targeted doublet, and the median overall survival was 56 months. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So, these results show that targeted doublet regimens resulted in a longer time to treatment failure and overall survival compared to any monotherapy in patients with chromophobe metastatic RCC and definitely provides valuable insights on treatment selection, albeit I would say there's still a small number of patients that were included in this retrospective analysis. Dr. Neeraj Agarwal: I completely agree this is a relatively small number of patients, but I decided to highlight the abstract given how rare the cancer is, and it is highly unlikely that we'll see large randomized clinical trials in patients with metastatic chromophobe renal cell carcinoma.  So, before we wrap up the podcast, what would you like to tell us about Abstract 5009 which is titled, “A Phase II Trial of Pembrolizumab Platinum Based Chemotherapy as First Line Systemic Therapy in Advanced Penile Cancer: HERCULES (LACOG 0218) Trial.” Dr. Jeanny Aragon-Ching: I'm glad you brought this up, Neeraj. As our listeners may know, advanced penile squamous cell carcinoma has a poor prognosis with limited treatment options. From this perspective, the results of the LACOG 0218 trial are very important. As you mentioned, this was a phase 2 single-arm study evaluating the addition of pembrolizumab to platinum-based chemotherapy as first-line treatment in patients with metastatic or locally advanced penile squamous cell carcinoma not amenable to curative therapy. Patients enrolled received chemotherapy, namely 5-Fluorouracil with cisplatin or carboplatin and pembrolizumab 200 mg IV every 3 weeks for 6 cycles, followed by pembrolizumab 200 mg IV every 3 weeks up to 34 cycles. The primary endpoint was confirmed overall response rate by investigator assessment.  In the 33 patients eligible for the efficacy analysis, the confirmed ORR by investigator assessment was 39.4% and included one complete response and 12 partial responses. The confirmed ORR was 75% in patients with high TMB and 55.6% in patients positive for HPV16, making TMB and HPV16 potential predictive biomarkers for efficacy in this study. Concerning the toxicity profile, any grade treatment-related adverse events were reported in around 92% of patients, and grade 3 or more treatment-related adverse events occurred in 51% of patients. 10.8% of patients discontinued treatment due to adverse events.  Dr. Neeraj Agarwal: Thank you, Jeanny. I would like to add that HERCULES is the first trial to demonstrate the efficacy of an immune checkpoint inhibitor in advanced penile squamous cell carcinoma with a manageable safety profile. Thus, the combination of ICI with platinum-based chemotherapy is a promising treatment for advanced penile squamous cell carcinoma and warrants further investigation.  Dr. Jeanny Aragon-Ching: I agree, Neeraj. Any final remarks before we conclude today's podcast? Dr. Neeraj Agarwal: Jeanny, I really want to thank you for your participation and valuable insights. Your contributions are always appreciated, and I sincerely thank you for taking the time to join us today. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. It was a pleasure.  Dr. Neeraj Agarwal:  As we bring this podcast to an end, I would like to acknowledge the significant advances happening in the treatment of patients with genitourinary cancers. During our upcoming 2024 ASCO Annual Meeting, there will be an array of different studies featuring practice-changing data presented by researchers and physicians from around the globe. I urge our listeners to not only participate in this event to celebrate these achievements, but to also play a role in sharing these cutting-edge data with healthcare professionals worldwide. Through our collective efforts, we can surely optimize the benefits of patients on a global scale.   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 podcast. Thank you very much.   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. 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. Jeanny Aragon-Ching    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. Jeanny Aragon-Ching:  Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono  Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,   Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics. 

Drs. Alicia Morgans and Jonathan Rosenberg share their insights into therapeutic sequencing in patients with advanced urothelial cancer, reviewing patient selection and timing, options following progression on immunotherapy, and future therapeutic agents such as HER2‑targeted ADCs.

Visit NascentMC.com for medical writing assistance. Visit learnAMAstyle.com for information on AI in Medical Writing and Editing - **mRNA Anti-EBV Cancer Vaccine**: The novel mRNA therapeutic cancer vaccine WGc-043 has been approved for clinical trials by the FDA, targeting Epstein-Barr virus (EBV) related cancers such as nasopharyngeal carcinoma and natural killer T-cell lymphoma. It stimulates the immune system to respond against EBV and associated malignancies, showing superior efficacy and safety in preliminary trials. A phase 1 clinical trial is currently focusing on patients who have failed second-line therapies, aiming to determine the optimal dose and evaluate safety and efficacy metrics. - **BTX-9341 for Breast Cancer**: The FDA has approved the investigational new drug application for BTX-9341, a novel cyclin-dependent kinase (CDK) 4/6 bifunctional degrader, intended for hormone receptor-positive, HER2-negative breast cancer resistant to existing CDK4/6 inhibitors. This drug targets and degrades CDK4/6 proteins, crucial for cancer cell cycle regulation, aiming to overcome resistance to current treatments. A phase 1 trial will assess its safety, biological activity, and efficacy both as monotherapy and combined with fulvestrant. - **Nivolumab Hyaluronidase Formulation**: The FDA has accepted a Biologics License Application for a subcutaneous formulation of nivolumab co-formulated with recombinant human hyaluronidase, enhancing convenience by reducing administration time compared to the intravenous version. This application includes all previously approved solid tumor indications for nivolumab, with a PDUFA date set for February 28, 2025. The subcutaneous version aims to provide faster and easier administration, supported by data from the Phase 3 CheckMate-67T study. - **ColoSense Colorectal Cancer Screening Test**: The FDA has approved ColoSense, a noninvasive colorectal cancer screening test using multi-target stool RNA for adults aged 45 and older at average risk. ColoSense, distinct from traditional FOBT tests, uses RNA biomarkers to detect CRC with high sensitivity and has shown promising results in clinical trials, detecting 93% of CRC cases and 45% of advanced adenomas in average-risk individuals. This new test offers a significant improvement in sensitivity and specificity over existing methods. For the complete shownotes visit nascentmc.com/podcast

In this second part, Matt Galski describes the OS signal data. We also look into the future.

Here is information on the latest US FDA approvals, the week of March 4 – March 8, 2024 ·         ChatGPT4 in medical writing and editing—visit learnAMAstyle.com ·       Nascentmc.com for medical writing assistance for your company. Visit nascentmc.com/podcast for full show notes   - **OTC Glucose Monitor**: The FDA has approved the Dexcom Stelo Glucose Biosensor System for over-the-counter sale, a first for a continuous glucose monitor. Designed for people aged 18 and older not using insulin, it helps manage diabetes with oral medications or monitors the impact of diet and exercise on blood sugar levels. Scheduled for release in Summer 2024, the system offers a 15-day sensor wear time and does not alert users to low blood sugar episodes.   - **Semaglutide in CVD Risk**: The FDA has approved semaglutide (Wegovy) for reducing cardiovascular risk in adults with known heart disease who are overweight or obese, specifically targeting the reduction of major adverse cardiovascular events. This approval makes semaglutide the first weight-loss medication also indicated for preventing life-threatening cardiovascular events in patients with established cardiovascular disease and obesity or overweight.   - **Juvederm Additional Indication**: JUVÉDERM® VOLUMA® XC, a hyaluronic acid dermal filler, has received FDA approval for treating moderate to severe temple hollowing in adults over 21, marking it as the first HA filler for this purpose. With effects lasting up to 13 months, clinical studies show significant improvement and patient satisfaction with facial symmetry post-treatment. This approval highlights Allergan Aesthetics' commitment to innovation in aesthetic treatments.   - **Nivolumab in mUC**: The FDA approved nivolumab in combination with cisplatin and gemcitabine for first-line treatment of metastatic urothelial carcinoma, based on significant improvements in survival outcomes from the CHECKMATE-901 trial. This expands nivolumab's indications, which include treatments for melanoma and lung cancer, among others, demonstrating its broad applicability in cancer treatment.   - **Zanubrutinib in FL**: The FDA has granted accelerated approval to zanubrutinib and obinutuzumab for relapsed or refractory follicular lymphoma patients after two or more systemic therapies. This combination targets key pathways in B cell survival, offering a new treatment option for patients. Approval was based on the ROSEWOOD trial, highlighting significant patient outcome improvements.   - **Donanemab and Alzheimer's**: The FDA has postponed the decision on the approval of Eli Lilly's donanemab for Alzheimer's treatment to convene an advisory meeting for further examination of safety and efficacy data, indicating a significant delay. This reflects the complex nature of Alzheimer's drug approval and Eli Lilly's confidence in donanemab's potential benefits.   - **Tocilizumab Biosimilar**: Tyenne® (tocilizumab-aazg), the first FDA-approved biosimilar to Actemra® for various inflammatory diseases, is now available in both IV and subcutaneous formulations. This approval introduces a new treatment option for patients with conditions like rheumatoid arthritis and juvenile idiopathic arthritis, emphasizing advancements in biosimilar medications.   - **Denosumab Biosimilars**: The FDA approved Jubbonti and Wyost as interchangeable biosimilars to Prolia and Xgeva, respectively, marking a first for biosimilars targeting the RANKL inhibitor used in osteoporosis and cancer-related bone conditions. These approvals offer new treatment options for managing bone health, underlining the importance of biosimilar development in expanding patient care.   - **Clobetasol Propionate Eye Drops**: The FDA's approval of clobetasol propionate 0.05% eye drops for post-operative eye inflammation and pain introduces the first ophthalmic formulation of this corticosteroid and the first new steroid in ophthalmology in over 15 years. Developed using proprietary nanoparticle technology for twice-daily dosing, this approval offers a new option for effective pain and inflammation management post-eye surgery.

In this week's episode we'll discuss the findings from a prospective trial of brentuximab vedotin with dacarbazine or nivolumab in older patients with classical Hodgkin lymphoma, learn more about CD20 antigen loss as a mechanism of resistance to mosunetuzumab in relapsed/refractory B-cell lymphomas, and discuss the role of trogocytosis in red blood cell antigen loss.

Today's episode of Lung Cancer Considered is part of our special series on seminal trials in thoracic oncology, focusing on the phase I study of the PD-1 inhibitor nivolumab. Hosts Dr. Narjust Florez and Dr. Stephen Liu discuss that study with guest Dr. Julie Brahmer from Johns Hopkins University. This podcast features surprise guest interviews with several doctors who were mentored by Dr. Brahmer.

After the 2024 Gastrointestinal Cancers Symposium, Jun Gong, MD, and Daneng Li, MD, sat down to discuss the most relevant trial data to have come from the conference. They convened for a live X Space hosted by CancerNetwork®. During the discussion, they covered different trials across the gastrointestinal space, which included those evaluating different disease states from hepatocellular carcinoma (HCC) to colorectal cancer (CRC), and those assessing circulating tumor DNA (ctDNA) dynamics. Gong, a hematologic oncologist focusing on gastrointestinal and genitourinary cancers at Cedars-Sinai Medical Center, and Li, an associate professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, each gave their perspective on the clinical trial data and discussed if they had implemented any of these study treatments into clinical practice.  The studies they covered included:  1.        Phase 3 NETTER-2 Trial (NCT03972488)1: - Investigated lutetium Lu 177 dotatate (Lutathera) plus octreotide vs octreotide alone for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). - Lutetium Lu 177 significantly improved progression-free survival (PFS) and overall response rate (ORR) compared with octreotide alone. - The agent may be considered for patients with high-grade GEP-NETs who desire significant tumor shrinkage. 2.        Phase 3 EMERALD-1 Trial (NCT03778957)2: - Studied transarterial chemoembolization (TACE) plus durvalumab (Imfinzi) with or without bevacizumab (Avastin) for unresectable HCC. - Durvalumab/bevacizumab plus TACE improved PFS compared with placebo plus TACE. - TACE may be preferred over transarterial radioembolization (TARE) due to faster patient recovery. 3.        Phase 3 CheckMate-8HW Trial3: - Evaluated nivolumab (Opdivo) plus ipilimumab (Yervoy) vs chemotherapy for first-line treatment of microsatellite instability-high/mismatch repair deficient metastatic CRC. - Nivolumab/ipilimumab demonstrated superior PFS compared with chemotherapy. - Chemotherapy may no longer be the standard first-line treatment for this patient population. 4.        BESPOKE Study (NCT04264702)4: - Assessed the impact of minimal residual disease (MRD) detected by ctDNA on disease recurrence in patients with stage II and III CRC receiving adjuvant chemotherapy. - MRD positivity was associated with worse disease-free survival (DFS). - ctDNA clearance at 12 weeks indicated improved DFS.  5.        GALAXY Trial5: - ctDNA is a promising biomarker that can be used to predict recurrence in patients with CRC. - Patients with ctDNA-positive disease had a worse DFS than patients with ctDNA-negative disease. - This suggests that ctDNA may be useful for making treatment decisions, but more research is needed before it can be used in clinical practice. 6.        Phase 3 FRESCO-2 Trial (NCT04322539)6: - Fruquintinib (Fruzaqla) improved the quality of life in patients with metastatic CRC when combined with best supportive care and significantly improved quality-adjusted time without symptoms of disease or toxicity compared with placebo and best supportive care. - The study showed positive effects on PFS, response rate, disease control, and duration of response with the fruquintinib combination. - The findings from this trial supported the FDA approval of fruquintinib for metastatic CRC in November 2023.7 References 1.        Singh S, Halperin D, Myrehaug S, et al. [177Lu]Lu-DOTA-TATE in newly diagnosed patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: primary analysis of the phase 3 randomized NETTER-2 study. J Clin Oncol. 2024(suppl 3):LBA588. doi:10.1200/JCO.2024.42.3_suppl.LBA588 2.        Lencioni R, Kudo M, Erinjeri J, et al. EMERALD-1: a phase 3, randomized, placebo-controlled study of transarterial chemoembolization combined with durvalumab with or without bevacizumab in participants with unresectable hepatocellular carcinoma eligible for embolization. J Clin Oncol. 2024;42(suppl 3):LBA432. doi.10.1200/JCO.2024.42.3_suppl.LBA432 3.        Andre T, Elez E, Van Cutsem E, et al. Nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) as first-line (1L) treatment for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): First results of the CheckMate 8HW study. J Clin Oncol. 2024;42(suppl_3):LBA768. doi.10.1200/JCO.2024.42.3_suppl.LBA768 4.        Kasi P, Aushev V, Ensor J, et al. Circulating tumor DNA (ctDNA) for informing adjuvant chemotherapy (ACT) in stage II/III colorectal cancer (CRC): interim analysis of BESPOKE CRC study. J Clin Oncol. 2024;42 (suppl _3):9. doi:10.1200/JCO.2024.42.3_suppl.9 5.        Yukami H, Nakamura Y, Mishima S, et al. Circulating tumor DNA (ctDNA) dynamics in patients with colorectal cancer (CRC) with molecular residual disease: Updated analysis from GALAXY study in the CIRCULATE-JAPAN. J Clin Oncol. 2024;42(suppl_3):6. doi:10.1200/JCO.2024.42.3_suppl.6 6.        Stintzing S, Tabernero J, Satoh T, et al. Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis of fruquintinib + best supportive care (BSC) compared with placebo + BSC in metastatic colorectal cancer (mCRC): results from the FRESCO-2 trial. J Clin Oncol. 2024;42(suppl 3):116. doi:10.1200/JCO.2024.42.3_suppl.116 7.        FDA approves fruquintinib in refractory metastatic colorectal cancer. FDA. News release. November 8, 2023. Accessed February 7, 2024. https://shorturl.at/isJW2

Visit nascentmc.com/podcast for full show notes [free course] ChatGPT4 in medical writing and editing at learnAMAstyle.com Nascentmc.com for medical writing assistance for your CME or Medical Communications company. Eplontersen for ATTR-CM Eplontersen received FDA Fast Track designation for treating transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) in adults, aiming to inhibit TTR protein production. Nivolumab for NSCLC The FDA accepted supplemental applications for nivolumab in resectable stage 2A to 3B non-small cell lung cancer (NSCLC) based on the CheckMate-77T trial showing improved survival rates. RSV Vaccine for Adults Aged 50 to 59 The FDA prioritizes review of GSK's Arexvy vaccine for RSV in adults aged 50-59 at risk of complications, expanding from its existing approval for those 60 and older. Spinal Cord Stimulation System The FDA approved Boston Scientific's WaveWriter Spinal Cord Stimulation Systems for chronic low back and leg pain treatment in non-surgery patients, based on the SOLIS trial results. OK-101 for Neuropathic Corneal Pain The FDA approved an IND application for OK-101, a first for treating neuropathic corneal pain (NCP), an Orphan disease, developed by OKYO Pharma Limited. Viz ICH Plus for Brain Bleed The FDA cleared Viz ICH Plus, an AI algorithm by Viz.ai for automating the identification and quantification of brain bleeds and structures in NCCT images. Vepdegestrant for MBC Vepdegestrant received FDA Fast Track designation for treating ER-positive/HER2-negative advanced or metastatic breast cancer in patients previously treated with endocrine therapy. VerTouch Spinal Puncture Device The FDA cleared VerTouch, a handheld imaging tool by IntuiTap Medical, designed to improve the accuracy of spinal punctures by providing a 2D image of lumbar spinal anatomy.

In this podcast, UROONCO RCC chief editor Dr. Carmen Mir interviews Prof. Nizar Tannir from the University of Texas, MD Anderson Cancer Center, USA, on the long-term follow-up data from the phase 3 CheckMate 214 trial: Nivolumab plus ipilimumab (NIVO+IPI) vs sunitinib (SUN) for first-line treatment of advanced renal cell carcinoma (aRCC). Prof. Tannir summarises the history and stability of the Checkmate 214 trial results over the last 8 years, before discussing the latest data from his presentation at ASCO GU24 in San Francisco.For more details on this trail, you can read the abstract on the UROONCO Kidney Cancer  educational platform.

This week on BackTable Urology, urologic oncologist Dr. Bogdana Schmidt (University of Utah) hosts a discussion with medical oncology experts Dr. Rana McKay (UC San Diego) and Dr. Neeraj Agarwal (University of Utah) on recent clinical trials from bladder, kidney, and prostate cancer research presented at the 2023 European Society for Medical Oncology (ESMO) Meeting. First, they discuss impactful data regarding bladder cancers, specifically the CheckMate 901 and the EV-302 trials which show improvement in overall survival and promise for urothelial carcinoma patients' quality of life. The conversation moves onto kidney-specific trials such as the LITESPARK-005, which offers improved progression-free survival for patients through the use of belzutifan. The panel rounds off by discussing the progress made in prostate-specific trials with emphasis on the EMBARK and SPLASH trials involving Lutetium therapy. Finally, the doctors discuss the trend towards personalized treatment plans based on the unique goals and health requirements of the patients. --- SHOW NOTES 00:00 - Discussion on Urothelial Carcinoma: CheckMate 901 and EV-302 11:22 - Discussion on Kidney Cancer: LITESPARK-005 23:53 - Discussion on Prostate Cancer: EMBARK 31:41 - Discussion on Prostate Cancer: SPLASH vs PSMA 36:39 - Future Directions for Lutetium Therapy for Prostate Cancer 37:50 - Closing Remarks and Future Expectations --- RESOURCES CheckMate 901 Trial Investigators. Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma. https://www.nejm.org/doi/full/10.1056/NEJMoa2309863 LBA6 EV-302/KEYNOTE-A39: Open-label, randomized phase III study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (Chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC). https://www.sciencedirect.com/science/article/pii/S0923753423042709 LBA88 Belzutifan versus everolimus in participants (pts) with previously treated advanced clear cell renal cell carcinoma (ccRCC): Randomized open-label phase III LITESPARK-005 study. https://www.sciencedirect.com/science/article/pii/S0923753423042345 LBA02-09 EMBARK: A Phase 3 Randomized Study of Enzalutamide or Placebo Plus Leuprolide Acetate and Enzalutamide Monotherapy in High-risk Biochemically Recurrent Prostate Cancer. https://pubmed.ncbi.nlm.nih.gov/37119051/ 177Lu-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy of Metastatic Castration-Resistant Prostate Cancer: Safety and Efficacy. https://pubmed.ncbi.nlm.nih.gov/26795286/

Drs. Neeraj Agarwal and Jeanny Aragon-Ching discuss several key abstracts to be presented at the 2024 ASCO GU Cancers Symposium, including sequencing versus upfront combination therapies for mCRPC in the BRCAAway study, updates on the CheckMate-9ER and CheckMate-214 trials in ccRCC, and a compelling real-world retrospective study in mUC of patients with FGFR2 and FGFR3 mutations. TRANSCRIPT Dr. Neeraj Agarwal: Hello, everyone, and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the podcast today. I am the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah's Huntsman Cancer Institute, and editor-in-chief of ASCO Daily News. I am delighted to welcome Dr. Jeanny Aragon-Ching, a genitourinary oncologist and the clinical program director of Genitourinary Cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing key posters and oral abstracts that will be featured at the 2024 ASCO Genitourinary Cancer Symposium, which is celebrating 20 years of evolution in GU oncology this year.  You will find our full disclosures in the transcript of this podcast, and disclosures of all guests on the podcast at asco.org/DNpod.  Jeanny, it's great to have you on the podcast today to highlight some key abstracts for our listeners ahead of the GU meeting. Dr. Jeanny Aragon-Ching: Thank you so much, Neeraj. It's an honor to be here. Dr. Neeraj Agarwal: Jeanny, as you know, this year we are celebrating the 20th anniversary of the ASCO GU Cancers Symposium, and judging from this year's abstracts, it's clear that this meeting continues to play a major role in advancing GU cancer research. Dr. Jeanny Aragon-Ching: Indeed, Neeraj. This year's abstracts reflect the important strides we have made in GU cancers. So, let's start with the prostate cancer abstracts. What is your takeaway from Abstract 19 on BRCAAway, which will be presented by Dr. Maha Hussein, and of which you are a co-author? As our listeners know, several PARP inhibitor combinations with second-generation androgen receptor pathway inhibitors, or ARPIs, have recently been approved as first-line treatment for patients with metastatic castrate-resistant prostate cancer, or metastatic CRPC, and the question of sequencing PARP inhibitors and ARPIs instead of combining them has emerged. From that perspective, the results of the BRCAAway trial are very important. Can you tell us a little bit more about this abstract, Neeraj?  Dr. Neeraj Agarwal: I totally agree with you, Jeanny. The BRCAAway study attempts to answer the crucial questions regarding sequencing versus upfront combination of therapies in the mCRPC setting. It is a phase 2 trial of abiraterone versus olaparib versus abiraterone with olaparib in patients with mCRPC harboring homologous recombination repair mutations. Enrolled patients had mCRPC disease and no prior exposure to PARP inhibitors or ARPIs or chemotherapy in the mCRPC setting and had BRCA1 or BRCA2 or ATM mutations. As previously mentioned, these patients were randomized to 3 arms: abiraterone monotherapy at 1000 milligrams once daily, or olaparib monotherapy at 300 milligrams twice daily, or the combination of abiraterone and olaparib. The primary endpoint was progression-free survival per RECIST 1.1 or Prostate Cancer Working Group 3-based criteria or clinical assessment or death, so, whichever occurred first was deemed to be progression.   Secondary endpoints included measurable disease response rates, PSA response rate, and toxicity. This was a relatively small trial with 21 patients in the combination arm, 19 patients in the abiraterone monotherapy arm, and 21 patients in the olaparib monotherapy arm. It should be noted that 26% of patients had received docetaxel chemotherapy in the hormone-sensitive setting, and only 3% of patients had any prior exposure to an ARPI, and these were darolutamide or enzalutamide or in the non-metastatic CRPC setting.  The results are very interesting. The median progression-free survival was 39 months in the combination arm, while it was 8.4 months in the abiraterone arm and 14 months in the olaparib arm. An important finding that I would like to highlight is that crossover was also allowed in the monotherapy arms. Of the 19 patients receiving abiraterone, 8 crossed over to receive olaparib, and of the 21 patients receiving olaparib, 8 crossed over to the abiraterone arm. The median PFS from randomization was 16 months in both groups of patients who received abiraterone followed by olaparib or those who received olaparib followed by abiraterone. This is striking when compared to 39 months in patients who started therapy with the combination therapy of abiraterone with olaparib. Dr. Jeanny Aragon-Ching: Thank you so much for that wonderful summary, Neeraj. So the key message from this abstract is that combining olaparib and abiraterone upfront seems to be associated with improvement in PFS compared to just sequencing those agents. Dr. Neeraj Agarwal: Exactly, Jeanny. I would like to add that these results are even more important given that in real-world practice, only half of the patients with mCRPC receive a second-line treatment. Based on these results, upfront intensification with a combination of an ARPI plus a PARP inhibitor in the first-line mCRPC setting seems to have superior efficacy compared to sequencing of these agents. Dr. Jeanny Aragon-Ching: Thank you so much. Now, moving on to a different setting in prostate cancer, there were a couple of abstracts assessing transperineal biopsy compared to the conventional transrectal biopsy for the detection of prostate cancer. So let's start with Abstract 261. Neeraj, can you tell us a little bit more about this abstract? Dr. Neeraj Agarwal: Sure, Jeanny. So, in Abstract 261 titled "Randomized Trial of Transperineal versus Transrectal Prostate Biopsy to Prevent Infection Complications," Dr. Jim Hugh and colleagues led a multicenter randomized trial comparing these 2 approaches, so, transperineal biopsy without antibiotic prophylaxis with transrectal biopsy with targeted prophylaxis in patients with suspected prostate cancer. The primary outcome was post-biopsy infection. Among the 567 participants included in the intention-to-treat analysis, no infection was reported with the transperineal approach, while 4 were detected with the transrectal approach, with a p-value of 0.059. The rates of other complications, such as urinary retention and significant bleeding, were very low and similar in both groups. The investigators also found that detection of clinically significant cancer was similar between the 2 techniques and concluded that the transperineal approach is more likely to reduce the risk of infection without antibiotic prophylaxis. Dr. Jeanny Aragon-Ching: So the key takeaway from this abstract sounds like office-based transperineal biopsy is well-tolerated and does not compromise cancer detection, along with better antibiotic stewardship and health care cost benefits.  Moving on to Abstract 273, also comparing these two approaches, what would be your key takeaway message, Neeraj?  Dr. Neeraj Agarwal: In this Abstract 273, titled "Difference in High-Risk Prostate Cancer Detection between Transrectal and Transperineal Approaches," Dr. Semko and colleagues found that the transperineal biopsy based on MRI fusion techniques was also characterized by a higher possibility of detecting high-risk prostate cancer and other risk factors as well, such as perineural and lymphovascular invasion or the presence of cribriform pattern, compared to the conventional transrectal method. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So we can see that the transperineal approach is gaining more importance and could be associated with more benefits compared to the conventional methods.   Let's now switch gears to kidney cancer, Neeraj. Dr. Neeraj Agarwal: Sure, Jeanny. Let's start by highlighting Abstract 361, which discusses patient-reported outcomes of the LITESPARK-005 study. So what can you tell us about this abstract, Jeanny?  Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So as a reminder to our listeners, based on the LITESPARK-005 trial, it was a Phase 3 trial looking at belzutifan, which is an inhibitor of hypoxia inducible factor 2 alpha or I'll just call HIF-2 alpha for short, was very recently approved by the FDA as a second-line treatment option for patients with advanced or metastatic clear cell renal cell carcinoma after prior progression on immune checkpoint and antiangiogenic therapies. The title of Abstract 361 is "Belzutifan versus Everolimus in Patients with Previously Treated Advanced RCC: Patient-Reported Outcomes in the Phase 3 LITESPARK-005 Study," and this will be presented by Dr. Tom Pells at the meeting. At a median follow-up of 25.7 months, the median duration of treatment with belzutifan was 7.6 months, while it was only 3.9 months with everolimus. At the time of data cutoff date for the second interim analysis, 22.6% of patients remained on belzutifan while only 5% remained on everolimus. In the quality of life questionnaires, the time of deterioration to various quality of life scores, as assessed by standardized scales, was significantly longer in patients randomized to the belzutifan arm compared to those in the everolimus arm. Also, patients in the everolimus arm had worse physical functioning scores. Dr. Neeraj Agarwal: Yes, Jeanny. In addition to the improved outcomes associated with belzutifan, patient-reported outcomes indicate better disease-specific symptoms and better quality of life among patients treated with belzutifan compared to everolimus. This is great news for patients with advanced renal cell carcinoma.  Now, Jeanny, can you please tell us about the two abstracts that reported longer follow-up of CheckMate 9ER and CheckMate 214 trials in untreated patients with advanced or metastatic renal cell carcinoma? Dr. Jeanny Aragon-Ching: Yes, Neeraj. So you are referring to Abstracts 362 and 363. Let's start with Abstract 362. This abstract reports the results after a median follow-up of 55 months in the CheckMate 9ER trial, comparing the combination of nivolumab and cabozantinib to sunitinib in patients with advanced RCC without any prior treatment, so first-line therapy. The primary endpoint was PFS per RECIST 1.1 as assessed by an independent central review. So there were key secondary outcomes including overall survival (OS), objective response rates, and safety. Consistent with prior analysis at a median follow-up time of 18.1 and 44 months, the combination of nivolumab and cabozantinib at a median follow up of 55.6 months continues to show a significant reduction in the risk of progression or death by 42% and in the risk of death by 23% compared to sunitinib.  Dr. Neeraj Agarwal: And Jeanny, what can you tell us about the efficacy results of this combination by IMDC risk categories? Dr. Jeanny Aragon-Ching: Similar to prior results in patients with intermediate to poor risk IMDC risk category, the combination treatment maintained significant efficacy and reduced the risk of progression or death by 44% and the risk of death by 27%. To put it simply, the update now shows a 15-month improvement in overall survival with the cabozantinib-nivolumab combination compared to sunitinib, which is amazing. Also, in patients with favorable IMDC risk group, which represented truly a small number of patients in the trial, there was a strong trend for improvement of outcomes as well. I would like to point out that no new safety concerns were identified. Dr. Neeraj Agarwal: So, it looks like the key message from this abstract is that with longer follow-up, the combination of nivolumab and cabozantinib maintains a meaningful long-term efficacy benefit over sunitinib, supporting its use for newly diagnosed patients with advanced or metastatic renal cell carcinoma.   Let's move on to Abstract 363, which compares nivolumab with ipilimumab to sunitinib in first-line advanced renal cell carcinoma. What would you like to tell us about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Yes, Neeraj. The title of this abstract is "Nivolumab plus Ipilimumab versus Sunitinib for the First-Line Treatment of Advanced RCC: Long-Term Follow-Up Data from the Phase 3 CheckMate 214 Trial." In this abstract, Dr. Tannir and colleagues report outcomes with the longest median follow-up in first-line advanced RCC setting for any clinical trial. So the median follow-up now is about 18 months. The primary endpoints were OS, PFS, and objective response rates, as assessed by an independent review according to RECIST 1.1 criteria in the intermediate to poor risk IMDC risk group, which is the intent-to-treat (ITT) analysis, while secondary outcomes included the same outcomes in the ITT population of patients. Although the progression-free survival was similar in both arms, the combination of nivolumab-ipilimumab reduced the risk of death by 28% compared to sunitinib in the ITT population of patients. When stratifying the results by IMDC risk groups, the combination arm of nivolumab-ipilimumab showed significant improvement in the intermediate to poor risk group, but there was no difference in the favorable risk group. But in the study, no new safety signals were identified. Dr. Neeraj Agarwal: Thank you, Jeanny, for such a comprehensive description of the results of these two studies. I'd like to add that the median overall survival of patients with metastatic renal cell carcinoma in the ITT population in the CheckMate 214 trial has now reached 53 months, which would have been unimaginable just a decade ago. This is wonderful news for our patients. So the key takeaway from these two abstracts would be that immune checkpoint inhibitor-based combinations remain the backbone of first-line advanced renal cell carcinoma treatment.  Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. This is wonderful news for all of our patients, especially for those who are being treated for first-line therapy.  Now, let's move on to the bladder cancer abstracts. We have two exciting abstracts from the UNITE database. What are your insights on Abstract 537, titled "Outcomes in Patients with Advanced Urethral Carcinoma Treated with Enfortumab Vedotin After Switch-Maintenance of Avelumab in the UNITE Study"? Dr. Neeraj Agarwal: As our listeners know, enfortumab vedotin is an antibody-drug conjugate that binds to a protein called Nectin 4 expressed on bladder cancer cells. In this abstract, Dr. Amanda Nizam and colleagues describe outcomes in 49 patients receiving third-line enfortumab vedotin after prior progression on platinum-based therapy and maintenance avelumab. At a median follow-up of 8.5 months, the median progression-free survival was 7 months and the median overall survival was 13.3 months with enfortumab vedotin in this treatment-refractory setting, the objective response rates were 54%. The message of this study is that enfortumab vedotin is an effective salvage therapy regimen for those patients who have already progressed on earlier lines of therapies, including platinum-based and immunotherapy regimens. Dr. Jeanny Aragon-Ching: Thank you, Neeraj, for that comprehensive review.  I want to focus on another patient population in the UNITE database, which is the use of fibroblast growth factor receptor (FGFR) alterations. Can you tell us more about the sequencing now of erdafitinib and enfortumab vedotin in these patients with metastatic urothelial cancer, as discussed in Abstract 616? Dr. Neeraj Agarwal: Sure, Jeanny. As a reminder, erdafitinib is a fibroblast growth factor receptor kinase inhibitor approved for patients with locally advanced or metastatic urothelial carcinoma harboring FGFR2 or FGFR3 alterations after progression on platinum-based chemotherapy. However, the optimal sequencing of therapies in these patients is unclear, especially with enfortumab vedotin being approved in the salvage therapy setting and now in the frontline therapy setting.  So in this retrospective study, all patients with metastatic urothelial carcinoma had FGFR2 or FGFR3 alterations. Dr. Cindy Jiang and colleagues report outcomes in 24 patients receiving enfortumab vedotin after erdafitinib, 15 patients receiving erdafitinib after enfortumab vedotin, and 55 patients receiving enfortumab vedotin only. This is a multicenter national study. Interestingly, patients receiving both agents had a longer overall survival in a multivariate analysis, regardless of the treatment sequencing, than patients receiving enfortumab vedotin alone or only with a hazard ratio of 0.52. The objective response rate of enfortumab vedotin in the enfortumab vedotin monotherapy arm was 49%. When these agents were sequenced, the objective response with enfortumab vedotin was 32% after erdafitinib and 67% when used before erdafitinib. Dr. Jeanny Aragon-Ching: Thank you so much, Neeraj. I think these are important real-world data results, but I would like to point out that larger and prospective studies are still needed to confirm these findings, especially regarding the outcome of erdafitinib after enfortumab vedotin, particularly when the latter is used in the first-line setting. Dr. Neeraj Agarwal: I totally agree, Jeanny. Now, let's discuss some abstracts related to disparities in the management of patients with genitourinary cancers.  Dr. Jeanny Aragon-Ching: Sure, actually, I would like to discuss 2 abstracts related to disparities in patients with prostate cancer. So the first one, Abstract 265, titled "Patient-Provider Rurality and Outcomes in Older Men with Prostate Cancer." In this study, Dr. Stabellini, Dr. Guha and the team used a SEER Medicare-linked database that included more than 75,000 patients with prostate cancer. The primary outcome was all-cause mortality, with secondary outcomes included prostate cancer-specific mortality. The investigators showed that the all-cause mortality risk was 44% higher in patients with prostate cancer from rural areas who had a provider from a non-metropolitan area compared to those who were in a metropolitan area and had a provider also from a metropolitan area. Dr. Neeraj Agarwal: Those are very important data and highlight the healthcare disparities among the rural population with prostate cancer that still exist.  So what is your key takeaway from Abstract 267, titled "Rural-Urban Disparities in Prostate Cancer Survival," which is a population-based study? Dr. Jeanny Aragon-Ching: Of course. This abstract discusses, actually, a very similar issue regarding access to healthcare among rural versus urban patients. In this study, Dr. Hu and Hashibe and colleagues and team at the Huntsman Cancer Institute assessed all-cause death and prostate cancer-related death risk in a retrospective study in which patients with prostate cancer based on rural versus urban residencies looked at 18,000 patients diagnosed with prostate cancer between 2004 and 2017. 15% lived in rural counties. Similar to the prior abstract we talked about, patients living in rural areas had about a 19% higher risk of all-cause mortality and a 21% higher risk of prostate cancer-specific mortality in comparison to patients living in urban areas. Dr. Neeraj Agarwal: So Jeanny, we can say that both of these abstracts, led by different groups of investigators, highlight that patients with prostate cancer living in rural areas have inferior survival outcomes compared to those living in urban areas, and it is time to focus on the disparities experienced by the rural population with prostate cancer.  Dr. Jeanny Aragon-Ching: Yeah, absolutely Neeraj. I concur with your thoughts.  So, any final thoughts before we wrap up the podcast today? Dr. Neeraj Agarwal: Yes, before concluding, Jeanny, I want to express my gratitude for your participation and the valuable insights you have shared today. Your contributions are always appreciated, and I sincerely thank you for taking the time to join us today.   As we bring this podcast to a close, I would like to highlight the significant advances happening in the treatment of patients with genitourinary cancers during our upcoming 2024 ASCO GU meeting. Many studies featuring practice-impacting data will be presented by investigators from around the globe. I encourage our listeners to not only participate at this event to celebrate these achievements, but to also play a role in disseminating these cutting-edge findings to practitioners worldwide. By doing so, we can collectively maximize the benefit for patients around the world.  And thank you to our listeners for joining us 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 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. Guest speakers express their own opinions, experience, and conclusions. Guest statements on the podcast do not necessarily reflect 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. Jeanny Aragon-Ching    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. Jeanny Aragon-Ching:    Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono  Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,   Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics. 

Dr Weber discusses the FDA approval of adjuvant nivolumab for patients with completely resected stage IIB/C melanoma, key efficacy data from the CheckMate76K trial, and potential future directions for PD-1 inhibitor–based combinations in the melanoma treatment paradigm.

Check out our free downloads at nascentmc.com: Implementing AMA Style – 8 Things to Get Right in Your Next Project Needs Assessments – 7 Essentials for Getting Funded Working With Your Medical Writer – 8 Ways to Get the Most out of Them See the full write ups for today's episode at nascentmc.com/podcast  Here are the highlights: BIMZELX (bimekizumab) for Moderate-to-Severe Plaque Psoriasis: The FDA approved BIMZELX for treating moderate-to-severe plaque psoriasis, making it the first psoriasis treatment targeting interleukin 17A and interleukin 17F. The approval follows data from Phase 3 trials and comes after a prior delay due to COVID-related travel restrictions. Neoadjuvant Pembrolizumab for NSCLC: The FDA approved pembrolizumab for neoadjuvant and post-surgical adjuvant treatment in patients with resectable non-small cell lung cancer, adding to its indications in multiple tumor types. The approval was based on the phase 3 KEYNOTE-671 trial data. Adjuvant Nivolumab for Stage IIB/C Melanoma: The FDA granted approval to nivolumab for adjuvant treatment of melanoma in patients aged 12 and older with resected stage IIB or IIC disease, addressing the need to reduce the risk of recurrence. This is supported by the CheckMate76K trial data. Zilucoplan for Myasthenia Gravis: UCB Pharma's zilucoplan, a complement C5 inhibitor, received FDA approval for treating myasthenia gravis (MG), demonstrating rapid improvements in MG-specific efficacy outcomes based on the phase 3 RAISE study. IDP-126 (Cabtreo) First Triple-Combination Drug for Acne: Cabtreo, a triple combination topical gel for acne, received FDA approval as the first fixed-dosed, triple-combination treatment for patients aged 12 and older with acne vulgaris. Penbraya Meningococcal Vaccine in Adolescents: The FDA approved Penbraya, a vaccine covering the five most common serogroups causing meningococcal disease in adolescents, based on Phase 2 and Phase 3 trial data. It's administered as a two-dose series. Voxzogo in Dwarfism: Vosoritide (Voxzogo) was expanded for use in children under 5 with achondroplasia, the most common form of short-limbed dwarfism, after demonstrating safety and efficacy in this age group. QLOSI for blurry age-related near vision: The FDA approved QLOSI, a preservative-free eye solution, for the treatment of presbyopia, improving near visual acuity by pupil modulation and increasing depth of field. Maxigesic IV for Post-Op Pain: Maxigesic IV, a combination of paracetamol and ibuprofen, gained FDA approval for post-operative pain management, offering faster pain relief and reduced opioid usage. Xphozah for Chronic Kidney Disease: Tenapanor (Xphozah) was approved as an add-on therapy for patients with chronic kidney disease who can't tolerate or respond adequately to phosphate binders, based on phase 3 trial data, addressing high blood phosphorus levels. Zymfentra infliximab biosimilar for ulcerative colitis and Crohn's disease: Zymfentra, a subcutaneous infliximab biosimilar, received FDA approval for maintenance therapy in adults with moderately to severely active ulcerative colitis and Crohn's disease, based on LIBERTY-UC and LIBERTY-CD study findings.  Intro and outro music Garden Of Love by Pk jazz Collective    

In this podcast from ESMO 2023, UROONCO BCa associate editor Dr. Laura Mertens (NL) talks with Dr. Michiel Van Der Heijden (NL) on his abstract “Nivolumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin alone for previously untreated unresectable or metastatic urothelial carcinoma: results from the phase 3 CheckMate 901 trial”. Dr. Van Der Heijden shares details on the design of the trial and the late-breaking results that he presented at ESMO 2023. Primary endpoints were met with overall survival (OS) and progression-free survival (PFS). Dr. Van Der Heijden also talks about the secondary endpoints, such as complete response rate, durability. For more details on this trial, you can read this abstract on the UROONCO Bladder Cancer educational platform.

This week we discuss the continued push to introduce 2nd generation androgen inhibitors earlier into treatment with the EMBARK trial. Nivolumab and pembrolizumab, pemrolizumab and nivolumab. Again and again. Their role (and approvals) for adjuvant melanoma make sense. But what to think about their use for NSCLC in the neoadjuvant setting? West commentary: https://dailynews.ascopubs.org/do/should-induction-chemoimmunotherapy-lead-us-broaden-our-definition-resectability-nsclc

Discussing two important lymphoma studies, POLARIX which led to the approval of Polatuzumab in DLBCL patients and SWOG S1826 comparing Nivolumab vs. BV with AVD in Hodgkin's Lymphoma patients with Dr. Jonathan Friedberg. In discussion with the lead author, Dr. Jonathan Friedberg - Director of Wilmot Cancer Institute, Professor of Medicine at University of Rochester Medical Center, and Editor-in-Chief at Journal of Clinical Oncology (JCO).

Drs Sapna Patel and Yana Najjar analyze the data and share their approach to frontline therapy. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/989035). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134 https://pubmed.ncbi.nlm.nih.gov/36166727/ Sequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated BRAF-Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial https://pubmed.ncbi.nlm.nih.gov/36049147/ Long-Term Outcomes of Patients With Active Melanoma Brain Metastases Treated With Combination Nivolumab Plus Ipilimumab (CheckMate 204): Final Results of an Open-Label, Multicentre, Phase 2 Study https://pubmed.ncbi.nlm.nih.gov/34774225/ Health-related Quality of Life With Nivolumab Plus Relatlimab Versus Nivolumab Monotherapy in Patients With Previously Untreated Unresectable or Metastatic Melanoma: RELATIVITY-047 Trial https://pubmed.ncbi.nlm.nih.gov/37167764/ Overall Survival With Combined Nivolumab and Ipilimumab in Advanced Melanoma https://pubmed.ncbi.nlm.nih.gov/28889792/ Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial https://pubmed.ncbi.nlm.nih.gov/30811280/ Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915) https://pubmed.ncbi.nlm.nih.gov/36162037/ Single-Agent PD-1 Blockade Is "Treatment of Choice" for Desmoplastic Melanoma https://pubmed.ncbi.nlm.nih.gov/37071762/ Single-agent Pembrolizumab May Benefit Patients With Rare Type of Skin Cancer https://www.aacr.org/about-the-aacr/newsroom/news-releases/single-agent-pembrolizumab-may-benefit-patients-with-rare-type-of-skin-cancer/ Atezolizumab, Vemurafenib, and Cobimetinib as First-Line Treatment for Unresectable Advanced BRAFV600 Mutation-Positive Melanoma (Imspire150): Primary Analysis of the Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/32534646/ Overall Survival Benefit With Tebentafusp in Metastatic Uveal Melanoma https://pubmed.ncbi.nlm.nih.gov/34551229/ Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis https://pubmed.ncbi.nlm.nih.gov/28056206/ Single-Agent Anti-PD-1 or Combined With Ipilimumab in Patients With Mucosal Melanoma: An International, Retrospective, Cohort Study https://pubmed.ncbi.nlm.nih.gov/35716907/ CheckMate 067: Long-Term Outcomes in Patients With Mucosal Melanoma. https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.10019 A Randomized Phase 2 Trial of Encorafenib + Binimetinib + Nivolumab Vs Ipilimumab + Nivolumab In BRAFV600-Mutant Melanoma Brain Metastases https://www.swog.org/clinical-trials/s2000

There is ongoing progress in the urothelial carcinoma treatment landscape, but after radical resection, what adjuvant options are there for your patient? Special guest Shilpa Gupta, MD, joins us to discuss the various ways to individually approach the adjuvant treatment setting for your patients with radically resected urothelial carcinoma along with their multidisciplinary care team. Dr. Gupta is a genitourinary oncologist at the Cleveland Clinic. She has led several investigator-initiated trials in genitourinary cancers, help leadership roles within National Cancer Institute Trials, and is the chair of the Alliance-led phase 3 trial in bladder cancer, co-chair of the Southwest Chemotherapy Study Group (SWOG) S1206 trial in prostate cancer and SWOG champion of the Alliance A031701 trial in bladder cancer.Learn more about an adjuvant treatment option for patients with urothelial carcinoma.https://www.opdivohcp.com/efficacy/uc/adjuvantINDICATIONOPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.IMPORTANT SAFETY INFORMATIONSevere and Fatal Immune-Mediated Adverse ReactionsImmune-mediated adverse reactions listed herein may not include all possible severe and fatal immune- mediated adverse reactions.Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO. Early identification and management are essential to ensure safe use of OPDIVO. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment with OPDIVO. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.Withhold or permanently discontinue OPDIVO depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.Immune-Mediated PneumonitisOPDIVO can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (

JCO PO author Dr. Brandon Huffman shares insights into his JCO PO article, “Analysis of Circulating Tumor DNA to Predict Risk of Recurrence in Patients With Esophageal and Gastric Cancers” and discusses the article's findings of ctDNA levels in the preoperative, postoperative, and surveillance settings in patients with EGC. Host Dr. Rafeh Naqash and Dr. Huffman discuss ctDNA assessments, treatment paradigms and interventions, and tumor-informed assays. TRANSCRIPT Dr. Abdul Rafeh Naqash: Hello, and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, social media editor for JCO Precision Oncology, and I'm also an Assistant Professor in Medical Oncology at the OU Stephenson Cancer Center. Today, I am excited to be joined by Dr. Brandon Huffman. Dr. Huffman is a gastrointestinal medical oncologist, and he's also an instructor in medicine at the Dana-Farber Cancer Institute at the Harvard Medical School. He's the lead author on today's JCO Precision article, "Analysis of Circulating Tumor DNA to Predict Risk of Recurrence in Patients with Esophageal and Gastric Cancers."   Our guest's disclosures will be linked in the transcript.   Dr. Huffman, welcome to our podcast and thanks for joining us today. Dr. Brandon Huffman: Of course. Thanks for having me. Dr. Abdul Rafeh Naqash: For the sake of this discussion, we'll refer to each other using our first names. So, Brandon, exciting to have you today. We're going to talk about this very interesting topic on circulating tumor DNA and how your team used the ctDNA assessment in patients with esophageal and gastric cancers. For the sake of the listeners, could we start by asking you what are the current treatment paradigms for early-stage esophagogastric cancers? Since you practice this on a daily basis, what is the current approach, briefly, which will play into how this study looked at ctDNA in the context of early-stage esophagogastric cancers? Dr. Brandon Huffman: Yes, definitely. Thanks first for having me. Thanks for highlighting our work, and I'm really excited to talk with you about our manuscript and research today. To answer your question about how to treat localized esophagogastric cancer, it's a little bit more specific depending on where in the esophagus, GE junction or stomach where the tumors arise. For instance, we treat esophageal and upper gastroesophageal junction cancers with, often, chemoradiation, neoadjuvantly, and that is followed by surgery. And if there's a pathologic incomplete response, then many patients will get Adjuvant Nivolumab, a PD-one inhibitor, whereas the lower the tumor is in the upper GI tract, most often, perioperative chemotherapy is used for the lower GEJ and gastric cancers. Dr. Abdul Rafeh Naqash: Thank you so much. And I know, I think to some extent, if I remember correctly, immunotherapy has been incorporated into this paradigm. Is that a fair assessment? Dr. Brandon Huffman: That's exactly right. So, excitingly, we treat patients with neoadjuvant chemo or chemoradiation, and surgery is really the crux of the treatment paradigm for esophagogastric cancers in general. However, recently the CheckMate 577 clinical trial for the use of adjuvant Navolumab showed an improvement in disease-free survival in patients who had an incomplete path response. They used one year of Nivolumab compared to placebo. So it has recently become a standard of care where I practice, and I feel like a common practice around the country. Dr. Abdul Rafeh Naqash: Thank you so much. Now, going to the premise of this paper where you and your team basically looked at circulating tumor DNA as a prognostic marker in these patients that had early-stage esophagogastric cancers, was there a specific reason why you wanted to look at the early stage? What was the rationale for evaluating this biomarker in this patient population? Dr. Brandon Huffman: So, esophageal and gastric cancers affect a large number of patients every year. And unfortunately, despite our best efforts with curative intent therapy, over 50% recur within three years. So we know that there are pre surgical risk factors such as a larger bulky primary tumor or lymph node-positive disease that increase the risk for progression or recurrence after surgery. And we know, in addition, in other GI malignancies and other malignancies such as colorectal cancer, for instance, that the presence of circulating tumor DNA after surgical resection of localized tumors is associated with an increased risk of recurrence. So this has actually led to clinical trials investigating whether or not ctDNA can be integrated into the decision-making for adjuvant colorectal cancer treatment, such as ongoing trials such as the BESPOKE trial, COBRA, DYNAMIC trials that have recently been reported. The use of ctDNA is being used in other malignancies. And to give you a little bit of background, this project started when I was seeing patients with Dr. Sam Klempner at Mass General during my fellowship, where I was in the combined Dana-Farber/Mass General program. And he and others had begun collecting serial plasma samples on every patient we saw with esophagus, gastroesophageal junction and gastric cancers to assess for the presence or absence of ctDNA. And we used the tumor-informed ctDNA assay from Signatera, which, for those who aren't familiar, this is a ctDNA platform where a panel is built from the results of whole exome sequencing on the patient's FFPE tumor. The panel includes 16 patient-specific somatic single nucleotide variants for each patient, and it's new for each patient. Once that panel is built, the cell free DNA is tested from a plasma sample. And if there are two or more of the tumor-specific variants present, then they're considered ctDNA positive. So some of those colorectal cancer trials that I mentioned before are using this assay, and we wanted to investigate whether or not this high-risk population could be further assessed for risk of recurrence. Dr. Abdul Rafeh Naqash: Excellent. Thank you so much. And I know that a lot of these ctDNA based assessments have made inroads into the GI malignancy space, lesser in the other tumor types. I think we are all trying to catch up to what you guys are doing in the early-stage colon cancer space or the early-stage esophagogastric cancer space. So it's definitely very a interesting avenue to assess minimal residual or molecular residual disease. Now, going back to the methodology, I found it very interesting, and I think it's very important for listeners especially to understand the context of ctDNA assessments because I think a majority of oncologists are used to the liquid biopsy aspect. But this is not necessarily the liquid biopsy. It's somewhat different. So what I've understood, and I'd like to ask you to explain in the context of tumor-informed and tumor uninformed assays, what are the assays that are available, and how do they differ in terms of serial monitoring? And why is this ctDNA-based assessment somewhat different or more patient-customizable than our regular liquid biopsy assays, which are also blood based but not tumor-informed? Dr. Brandon Huffman: That is the question of the hour. And many different research projects are ongoing to try and identify which one is better, if one is better. I know that there are some commercial assays, for instance, that are not tumor-informed. They take a blood sample and then test for cell free DNA. The risk behind that is it's testing for common genetic mutations from a next-generation sequencing panel platform. And it may also detect CHIP variants or clonal hematopoiesis of indeterminate potential variants that aren't related to the underlying solid tumor malignancy. So a tumor-informed assay, for instance, such as the one that we used in this study, uses the patient's tumor and sequences it with whole exome sequencing and identifies very specific variants within the tumor that are only present within the tumor because they compare it also with a normal blood sample from the patient at the same time. And so they pick tumor-informed specific variants that then they test for on their assay. And that increases the sensitivity of the ctDNA assay so that you can really try to understand, is this cell free DNA that we are detecting related to the tumor or can we ignore it potentially? I don't know if we can necessarily ignore it in all honesty because it could affect- there's a lot of ongoing work that is looking at the risk of CHIP. But overall, this is specific for the primary tumor that we were investigating. Dr. Abdul Rafeh Naqash: I definitely agree with you there. I think the important point, as you mentioned, is that using the whole exome approach, in the blood and the tumor, you're able to eliminate the CHIP variants or the germline variants that may not be contributing. And that way you're able to specifically look at certain genetic alterations that eventually, I think using PCR-based approaches, you identify the same and quantify the same in the blood serially. And that's how this tumor-informed assay is somewhat unique and different. Now, going to the crux of this study, could you tell us a little about the patient population? I think you stratified patients. You had a pre-operative cohort, you had an MRD cohort, you had a surveillance cohort, and you had a cohort where you assessed ctDNA positivity at any time point. So, several different cohorts, and you assess recurrence-free survival in those cohorts. Could you tell us a little bit more about how you evaluated these cohorts? What were the selection criteria, and how many patient samples did you have for these different cohorts? Dr. Brandon Huffman: Absolutely. So, we aimed to determine the feasibility of testing ctDNA in patients with gastroesophageal cancer. And so, there were several clinicians from over 70 institutions across the United States who began prospectively collecting serial plasma samples for the presence or absence of the tumor-informed ctDNA. And they included patients from stages one through stage four, gastroesophageal cancer specifically, they included patients who were stages one through four with gastroesophageal cancer. They were collected at the discretion of the ordering clinicians and then incorporated into their routine clinical care as they saw fit. Within this dataset, we have a subset, a large number of patients that is unique to this dataset, specifically in that we have clinical outcomes, treatment, and follow-up data for the patients that were reported on the main findings in the paper. So, overall, we collected and analyzed over 900 plasma samples in almost 300 patients with gastroesophageal cancer, esophageal, gastroesophageal junction and gastric cancers. And in many of the analyses, we lumped them all together. But then we also wanted to separate it out because, as I mentioned before, the treatment paradigm does differ amongst a more proximal esophageal tumor compared to a distal gastric cancer. So, we focused a majority of our analyses on the detection of ctDNA and localized disease, which included 212 patients with stages one through three gastroesophageal cancer. And I would say we had three major findings. Most of the patients who were tested beforehand, which was a small subset, as I mentioned, this was pragmatic at the discretion of the ordering clinician, but most of the patients who were tested beforehand had positive preoperative ctDNA present. Of the patients who were tested for postoperative ctDNA at any time point, and then specifically within the different subsets of populations that we talked about, postoperative ctDNA was associated with at least a tenfold increased risk of recurrence in all subsets. And ctDNA detection postoperatively was independently associated with recurrence when controlling for age, sex, tumor location, and microsatellite status. So, a few of the populations that we wanted to test for, one in particular was the molecular residual disease, or MRD window. We labeled this MRD window as the time from surgical resection until 16 weeks. So, if patients were ctDNA positive within that window, we counted that in the primary outcome. And the reason that we chose the MRD window, in addition to this time point of 16 weeks - I should say that the 16 weeks is without any therapy postoperatively, so they have not been treated with any chemo or immunotherapy in this window. We thought that this MRD window was an interesting research topic because the CheckMate 577 Adjuvant Nivolumab clinical trial identified that 16 weeks was the window in which patients could be enrolled up until that timepoint to receive adjuvant nivolumab. So, we're thinking from a future project standpoint, a future clinical trial, perhaps, that if we have identified that patients who are ctDNA positive within this timepoint window, is there an increased risk for recurrence? Because if there is, then perhaps nivolumab intervention will decrease that risk or something that is escalated further. And that's a question that we don't have the answer for, a question that our data can't answer adequately. But it's an interesting one that I see the future questions that can be answered from these data. Dr. Abdul Rafeh Naqash: Thank you so much. And I agree with you there that this is a very intriguing approach of finding out whether treatment escalation has to be done based on ctDNA positivity, but also, conversely, treatment de-escalation, which there is a lot of emphasis being laid on, especially in the early phase trial in lung cancer, especially in the early setting when targeted therapies or immunotherapies are approved for one to three years, depending on what kind of therapy you're looking at. In those individuals that perhaps have negative ctDNA after one year, maybe therapy de-escalation would be a reasonable approach. So, definitely more interesting clinical trial ideas in this space focusing on ctDNA assessments. Now, one of the questions that comes to my mind is, when you use ctDNA-based assessments, initially, the patient gets biopsied, and it usually takes four to six weeks for ctDNA-based assessments to come back--I'm talking about tumor-informed assay results to come back, in my personal experience. So, could that potentially, or in your practice, how do you mitigate those delays? If you're trying to schedule a patient for surgery, for example, does that cause any delays in any care because you're trying to get the assessment done, or does your workflow proceed as planned and then you get the results and then subsequently you perhaps make a decision based on their ctDNA assessment? Dr. Brandon Huffman: At the present time, we are trying to gather more data to understand what we should do with the results that we're receiving. And I think the starting point of collecting serially to just understand the process is helpful. One of the questions we wanted to know that we weren't able to answer with this dataset was: is there lead time? In many cases, ctDNA detection can occur even a year prior to radiographic recurrence. In our case, because this was a pragmatic, clinically at the discretion of the investigators when they decided to test patients for ctDNA, there is heterogeneity among those who are ctDNA positive, and when they get their radiographic imaging, maybe they were moved up. I know in our practice with Dr. Klempner, when I was seeing these patients with him, it was a flag for us to order scans earlier in a patient that we might not have historically ordered so that we could then see, is there something intervenable? Maybe there was a positive lymph node on PET imaging that we could radiate or that wasn't included in the neoadjuvant radiation, for instance. So, we could not predict the lead time from positivity to radiographic recurrence, but I think that that's the hope is that we detected micrometastatic disease, my hope is that we can intervene in the future. But these data aren't able to quite answer that question perfectly. Dr. Abdul Rafeh Naqash: Sure. And there's definitely caveats to doing this in a pragmatic manner based on investigator assessments. Now, another question I was thinking of is, when you do do these ctDNA based assessments, and since these are tumor-informed, meaning you biopsy the tumor initially, you identify certain single nucleotide variants and those are the ones that you basically barcode and do PCR assessments using blood. We've learned time and again that tumors can change based on the kind of therapy that you give the patient. So, if your tumor is seeing FOLFOX nivolumab, or all the other novel therapies that you guys give in the setting, is there a chance that the tumor changes over time and you may not be able to capture those newer single-nucleotide variants that are coming up? It's just a provocative question, but I wanted to see what your thoughts are on that. Dr. Brandon Huffman: It's a great question. I don't entirely know the answer. I'll just be forthright about that. I do think that when designing these assays, they try to choose the more clonal rather than subclonal variants. And so the hope is that, despite the heterogeneity that we know occurs in esophagogastric cancers, we can eliminate that possibility. But you're right, there's no perfect way of knowing that. Dr. Abdul Rafeh Naqash: I really appreciate you using that word subclonal versus clonal. I think that perhaps makes a difference there. But again, more to do in this field to understand how the tumor evolves and whether it's the clonal mutation, subclonal mutation that needs to be followed. But definitely a lot of interesting work in this space that's ongoing, and, like you mentioned, there are ongoing trials, and both in the neoadjuvant adjuvant space, this field is definitely moving fast in the right direction. I briefly want you to highlight that one patient case study example that you had. And this was a patient with oligometastatic disease recurrence where you used the ctDNA assessment. And I do some of this in my daily practice, and I really found it useful to have this sort of a patient case example that elaborates in the bigger picture of how this kind of assessment works in a real-life scenario. So it's not just data, it's a patient's trajectory over the course of time where the treating physician was able to use this assay. Could you tell us a little bit more about this individual example here? Dr. Brandon Huffman: Yeah, absolutely. So this was a 56-year-old man that we saw in clinic with stage three esophageal adenocarcinoma, and was treated with the standard neoadjuvant cross chemoradiation, had an R0 resection with residual disease with a significant treatment effect. And there were lymph nodes that were positive on surgical resection with 39 lymph nodes removed. The patient recovered well and was followed with the standard of care radiographic and clinical surveillance. We also were looking for ctDNA, and what we noted was that there were, often you find these undulating pulmonary nodules that come and go, and they may or may not be infectious, and maybe there's one that's sub-centimeter that slowly grows, and what we found was that at about five months post-surgery, there was a positive ctDNA MRD, and we repeated it at short interval and noted a rising value, which this assay will give you a quantitative value. Once we did that, we ordered imaging and saw a nine-millimeter pulmonary nodule and ultimately biopsied it. It was there in the right upper lobe, and it was positive for metastatic adenocarcinoma. So we treated the patient with the standard FOLFOX plus Nivolumab and actually did SBRT, stereotactic body radiotherapy, to the lung metastasis. And his ctDNA became undetectable. So because FOLFOX is toxic, we transitioned to a maintenance of Nivolumab and he was on maintenance therapy for several months and had no radiographic evidence of disease and remained ctDNA negative for twelve months. So we biopsied the right upper lobe lung lesion. It was positive for metastatic adenocarcinoma, and then after a multidisciplinary discussion, we treated him with SBRT and then FOLFOX and Nivolumab and then dropped down to Nivolumab maintenance once his ctDNA was undetectable. That highlights the fact that this was an isolated recurrence, which we continued to monitor, and then he had another site of disease a few months later, and we did SBRT to that area while he maintained on just Nivolumab, and the ctDNA came down as well.   So I think, although it doesn't prove anything necessarily, other than demonstrating there is a correlation with the newly diagnosed metastatic disease, it does note that you can use this in dynamic ways, and if it really helps patients live longer, although this is anecdotal--who knows? If we hadn't done SBRT to that area, it was 9 mm. We could have waited until it grew, but then maybe some subclonal, more aggressive metastasis could have really put this patient in a much tougher situation. So it's an interesting case example, and there are several others that we could have put in here that are pretty similar. Dr. Abdul Rafeh Naqash: Thank you so much for highlighting that case. I couldn't agree more that there is a certain aspect to the ctDNA assessment, where in individuals like the example that you've highlighted here, this can provide lead time potentially and help with earlier management of perhaps more like oligometastatic disease rather than diffuse disease burden. And in that context, one of the questions that I was going to ask you, based on your data, was there any correlation of tumor burden preoperatively and ctDNA positivity after surgery that you guys were able to identify or thinking of identifying? Dr. Brandon Huffman: Unfortunately, with our data set, we weren't able to look at that assessment of comparing the overall tumor burden to the quantitative value. But it's an interesting one because we know that in other malignancies, for instance, if there is a correlation of overall disease burden, it also depends on the tumor type, but we also know that perhaps patients will respond differently to chemo or immunotherapy if they have a lower tumor burden, if they have a lower ctDNA value, potentially. I think that's an interesting question for a future project. Dr. Abdul Rafeh Naqash: Thank you so much, Brandon. We do like to talk a little bit about the person behind the work. So tell us a little bit more about yourself, your training, your interests, and some little advice for other early-career investigators who might be looking into a similar space and hopefully get inspired by the kind of work that you've done or are planning to do. Dr. Brandon Huffman: Sure. So, as I mentioned, when I started this project, I was in fellowship. I was seeing patients with Dr. Sam Klempner at Mass General, where I saw patients with him for a year, and as part of my clinical training in the Dana-Farber/Mass General HemOnc Fellowship. Since that time, I have graduated fellowship. I'm a GI Medical Oncologist at Dana-Farber Cancer Institute, and in the GI division, I see patients with all GI malignancies, and I focus on the development of clinical trials in upper GI malignancies, along with investigating the use of circulating tumor DNA as a biomarker, hopefully, we can understand whether it's a predictive biomarker that we can intervene upon in the future. I think the greatest advice that I received and that I will give to all future trainees; I'm not sure that I'm qualified to tell this to all the junior investigators, but here it is: Find yourself a mentor who really cares and invests in you and your ideas. I have that with Sam, and this project was an incredible part of my development as a junior investigator. I've asked really interesting questions. There are more questions that can be answered from this data set, and I'm excited for the opportunity. Dr. Abdul Rafeh Naqash: Thank you so much, Brandon. Thanks for taking the time to speak with us today and thank you for choosing JCO Precision Oncology as a destination for your work. Hopefully, we'll see more of this subsequently in the years to come. Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating, a review, and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/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. 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. Guest Bio Dr. Brandon Huffman, MD, is a gastrointestinal medical oncologist and Instructor in Medicine at Dana-Farber Cancer Institute and Harvard Medical School.  Guest Disclosures Brandon M. Huffman Stock and Other Ownership Interests: Doximity

Featuring perspectives from Dr Matthew Lunning, including the following topics: •      Potential role of polatuzumab vedotin/R-CHP in therapy for previously untreated diffuse large B-cell lymphoma (DLBCL) (00:00) •      Association between metabolic tumor volume and clinical outcomes with loncastuximab tesirine in the LOTIS-2 trial and axicabtagene ciloleucel in the ZUMA-7 trial (10:54) •      Chimeric antigen receptor (CAR) T-cell therapies for large B-cell lymphomas: Activity, tolerability and patient selection (22:16) •      Efficacy of and durable complete responses with bispecific antibodies in patients with DLBCL (36:48) •      Five-year results and overall survival update from the Phase III AUGMENT study evaluating rituximab and lenalidomide (R2) versus rituximab and placebo for relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (42:44) •      Activity and safety of tazemetostat in combination with (R2) in patients with R/R follicular lymphoma (FL) (44:52) •      Long-term clinical outcomes with CAR T-cell therapies for patients with R/R FL (46:50) •      Available data with and ongoing studies of bispecific antibodies for R/R FL (50:23) •      Design and outcomes of the SHINE and TRIANGLE studies in mantle cell lymphoma (MCL); evolving role of transplantation for MCL (1:00:38) •      Real-time monitoring of minimal residual disease in patients receiving acalabrutinib with (R2) for treatment-naïve MCL (1:13:29) •      Assessment of durable responses after brexucabtagene autoleucel for R/R MCL in the ZUMA-2 trial (1:15:29) •      High complete response rates with glofitamab for patients with heavily pretreated MCL (1:19:00) •      Nivolumab with ICE (ifosfamide/carboplatin/etoposide) as first salvage therapy for patients with high-risk R/R Hodgkin lymphoma (1:21:04) •      Efficacy and safety of camidanlumab tesirine in patients with R/R classical Hodgkin lymphoma (1:23:07) •      Importance of brain-to-vein time in patients receiving CAR T-cell therapy (1:25:37) CME information and select publications

Matt Galski presents his data. 

Description: Dr. Jasmin Jo interviews Dr. Michael Lim about his and his team's recent manuscript entitled: "Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter", published online in Neuro-Oncology in November 2022.

JCO PO author Dr. Shilpa Gupta, MD, Associate Professor of Medicine at the Cleveland Clinic and GU Medical Oncology Director, shares analysis on outcomes in real-world settings for metastatic urothelial carcinoma (mUC) patients. Host Dr. Rafeh Naqash and Dr. Gupta discuss the utility of tumor mutational burden (TMB) to determine treatment, and mUC patient response from immune checkpoint inhibitors (ICPI) as compared with carboplatin. Click here to read the article!   TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations. I am Dr. Rafeh Naqash, assistant professor of medicine at OU Stephenson Cancer Center. You're listening to the JCO Precision Oncology Conversations podcast.   Today I'll be talking with Dr. Shilpa Gupta, who is an associate professor of medicine at the Cleveland Clinic and also the GU Medical Oncology Director. And we'll be talking about their group's recent paper, ‘Tumor Mutational Burden as a Predictor of First-Line Immune Checkpoint Inhibitor Versus Carboplatin Benefit in Cisplatin-Unfit Patients With Urothelial Carcinoma'.   Full disclosures for our guest can be found on the article's publication page.   Hello and welcome to the podcast, Dr. Gupta. It's nice to have you here. For the sake of this podcast, we'll be referring to each other using our first names. So welcome and thanks for joining us today.   Dr. Shilpa Gupta: It's my pleasure to be here, Rafeh, I'm really excited about chatting about this paper with you. Thank you for the opportunity.   Dr. Rafeh Naqash: Thank you so much. So today we'll be discussing this interesting publication of yours, talking about biomarkers. And I often refer to biomarkers as the Pandora's Box for immune checkpoint inhibitors because definitely one size does not fit all. And reading through your paper, I saw a lot of interesting findings that you have defined in this publication. But for starters, what was the premise and background of why you wanted to study this question of tumor mutational burden as a biomarker in this patient population?   Dr. Shilpa Gupta: Yeah, that's a great question, Rafeh. The treatment paradigm for urothelial cancer patients has really evolved over the last many years. For example, patients who are eligible to receive cisplatin-based chemotherapy, that's the treatment of choice. And for patients who are not eligible to receive cisplatin due to a variety of reasons like chronic kidney disease, heart failure, peripheral neuropathy, poor performance status, or hearing loss, in the past, we used to treat them with gemcitabine and carboplatin, but outcomes were quite dismal with median overall survival less than six months or so. And then in 2017, the approval of pembrolizumab and atezolizumab as single agents was welcome news because these patients had more durable responses and survival was longer than historically with gemcitabine-carboplatin. And this is what became the standard of care based on the FDA expedited approval.   However, in 2018, the FDA restricted the use of immunotherapy only to those patients whose tumors had high PD-L1 or who were not eligible to receive carboplatin, based on the interim analysis from the phase three trials IMvigor130, which compared atezolizumab to gemcitabine-carboplatin, one of the cohorts for cis-ineligible patients, and KEYNOTE-361, which compared pembrolizumab to gemcitabine-carboplatin in the cis-ineligible cohort. And furthermore, recently, the FDA actually further restricted the label for pembrolizumab, because in the phase 3 study, even in high PD-L1 subgroups, pembrolizumab did worse than gemcitabine-carboplatin, regardless of their PD-L1 status. There were early deaths, lower response rates, and in the IMvigor130 study, we recently saw that atezolizumab was actually withdrawn for this indication altogether.   So there has been this attraction for PD-L1 for a long time, but now multiple studies in urothelial cancer have shown that PD-L1 is not a durable biomarker. And we wanted to see if there's other biomarkers which can be accessible at the point of care. And we wanted to study how tumor mutational burden can or cannot pan out as a treatment selection or complementary to clinical criteria. Right now, there's no biomarkers to guide treatment for patients in urothelial cancer for carboplatin or immunotherapy use. And that was the premise for the study.   Dr. Rafeh Naqash: Excellent. Thank you so much for that detailed understanding of why you decided to pursue this.   Now, from the listener standpoint when you define cisplatin-ineligible patients, in your practice, what is the percentage of patients that you see who are technically cisplatin-ineligible? Does comorbidity play an important role in determining which patients, or does it depend on your discussion with the patient? What are those factors that you would describe to define what cisplatin-ineligibility would constitute?   Dr. Shilpa Gupta: So historically, Matt Galsky and colleagues described cisplatin-ineligibility as patients with a creatinine clearance less than 60 mLs per minute, hearing loss greater than grade two, poor ECOG performance status two or higher, peripheral neuropathy, which is significant or significant heart failure. Now, those all make patients ineligible for cisplatin. Now, more recently, we know that we can safely give cisplatin as long as creatinine clearance is above 50. So for the real world, 50 is a threshold where we can use split dose cisplatin. And I'll say, given that bladder cancer or urothelial cancer is a disease of the elderly, median age being 71 years, a lot of our patients have these comorbidities, chronic kidney disease, diabetes, and whatnot, which precludes us from using cisplatin. So in the real world, I would say that around 50% of patients are ineligible to receive cisplatin.   Dr. Rafeh Naqash: Interesting. And that goes back to the point where not everything that resulted from clinical trials, or the data that we get, may not be exactly applicable to the real world patient population, as you have pointed out in this interesting paper. So going back to the manuscript now from a methodology perspective, what kind of data did you include to get to the results that we'll talk about next? What was the inclusion and what was the patient population in this analysis?   Dr. Shilpa Gupta: So the patient population basically were patients who had a confirmed diagnosis of metastatic urothelial cancer. And the databases we used were the US-wide Flatiron Foundation Medicine Clinical Genomic Database, which has patients who were listed as metastatic urothelial cancer. But in addition, they also had genomic testing performed from their tumors, and results were available. And we accessed the database between 2011 until April 2021. And all these patients had had genomic testing using Foundation Medicine assay. And this de-identified data was basically US-wide across 280 cancer clinics and that's around 800 sites of care. And there's a whole range of retrospective longitudinal clinical data that was available, derived from the electronic health records comprising patient-level structured and unstructured data and also their genomic information from the tumors. And there was clinical data including demographics, lab values, performance status, timing of treatment, exposure, as well as time of progression and survival.   We decided to include patients if they received a frontline single agent immunotherapy, no matter what it was, whether pembrolizumab, atezolizumab, Nivolumab, durvalumab or avelumab, or a carboplatin-based chemotherapy. And just for the readers, this is a retrospective review. So we just used these selected patients who got in these therapies. We also required that these patients had tumor mutational burden information available through the tissue biopsy and patients who received chemotherapy and immunotherapy together were excluded and details are present in the manuscript, but this was pretty much the broad selection criteria.   Dr. Rafeh Naqash: Thank you so much. And definitely a very representative patient population from a real world setting with different therapy and different other clinical variables that are relevant in the real world setting.   So from an analysis standpoint, you, from what I read, define both a predictive and a prognostic aspect to tumor mutational burden. Could you tell us more about those results and highlight some of the interesting findings from that perspective?   Dr. Shilpa Gupta: Yes, absolutely. So as you know, tumor mutation burden cut off of ten mutations per megabase is currently utilized by the FDA, whereby approval of pembrolizumab for tumor agnostic condition was made. So that's what we considered high versus low. And we found that in this, after propensity weighing in, the tumor mutational burden less than ten group, basically those patients did not benefit from checkpoint inhibitor single agent as compared to tumor mutational burden of ten or greater. And so basically, we found that patients who had tumor mutational burden ten or higher overall had more favorable progression-free survival time to next treatment, as well as overall survival when they got a single agent immune checkpoint inhibitor, as opposed to those who got carboplatin, and also when compared to those who had tumor mutational burden less than ten. So we also looked at PD-L1 information available from the genomic database, but it was only available for around 35% of patients and still we were able to see that PD-L1 did not correlate with any of these outcomes as we show in the paper.   Dr. Rafeh Naqash: I see. And as you mentioned, you show both time to treatment failure PFS being better in TMB high patients defined as ten mutations per megabase. I didn't specifically see results related to TMB high versus low in a carboplatin specific cohort. Is that analysis something that was looked at and trying to understand whether neoantigens in a platinum-based setting specifically make a difference whether high TMB is predictive there in the carboplatin setting. Was that looked at?   Dr. Shilpa Gupta: So yes, we looked at, in the Figure 4, for the comparison of the TMB and which we were looking at the checkpoint inhibitor versus chemo. So for TMB low the chemotherapy cohort had more favorable results. Is this what you were getting at?   Dr. Rafeh Naqash: Yeah, I think what I was specifically trying to look at, like you have shown in the paper, is TMB is predictive of benefit with checkpoint inhibitors and is also prognostic in the checkpoint inhibitor setting. So my question was more whether it had a prognostic implication in a carboplatin specific cohort. So meaning high TMB, whether it correlated with better outcomes with carboplatin therapy versus low TMB. So if that was looked at.   Dr. Shilpa Gupta: We didn't look at that specifically, we only compared whether high TMB did better with the immunotherapy or chemotherapy.   Dr. Rafeh Naqash: And some of the correlation of this in my mind comes from some data that people have looked at in the lung cancer setting, whether high TMB makes a difference and for example, resected lung cancer patients, which usually gets platinum-based adjuvant therapies. So that's why I was wondering if there's any correlation there. But this is definitely interesting.   Now, my next question was going to be in your manuscript you mentioned around 30% of patients had tumor mutational burden more than or equal to ten. Did you identify any other unique characteristics from any other mutational standpoint or a PD-L1 standpoint in the high TMB cohort?   Dr. Shilpa Gupta: Yes. So PD-L1 didn't really stand out to be a very steady biomarker in our experience. And this is also what was reflected in the phase three trials like DANUBE where they looked at the durvalumab and tremelimumab, IMvigor130 or KEYNOTE-361. So that was pretty consistent that these studies also showed TMB to be more useful in exploratory analysis. Of course, these patients were not stratified based on that. And we also looked at other emerging biomarkers, for example, F-TBRS and angiogenesis gene expression signatures as well as tGE3. And we need to evaluate them in a separate study to see what pans out.   But for now, I think as far as in the real world, we are looking at a lot of genomic testing being done and right now we really don't know how to use that for making treatment decisions, right? PD-L1 has really phased out as of any utility whatsoever. And using TMB; I think in addition to the clinical characteristics, like when possible, we should be offering patients carboplatin. There's no doubt about that for cisplatin ineligible patients. But there's those patients who, if they're refusing chemotherapy and we really can't make a case for giving them single agent immunotherapy, I think TMB can come in handy to justify and make sure that we're not doing them a disservice by not giving carboplatin. And I think future trials need to use this biomarker in a prospective setting to further establish its utility.   Dr. Rafeh Naqash: Definitely, I agree it's a case-by-case situation from a patient standpoint to determine what therapy is appropriate for the patient and what is most realistic, what is the expectation that the patient has, from that treatment.   Now, from a TMB standpoint, one of the ongoing debates is if it is a binary cut off or whether it could be tertiles for a certain tumor type or quartiles. Was there any subanalysis or any subsequent study that your team would be looking at from a TMB cut off standpoint? Maybe a higher cut off would mean a better outcome and maybe lesser duration of therapy in those patients. Is that somewhat of a consideration?   Dr. Shilpa Gupta: Yeah, that's a great question, Rafeh. And I think the reason we stuck to it as a binary end point is because that's the FDA definition, so people don't try to extrapolate based on anything higher or lower. But yeah, that's a great question. And I know in lung cancer they're looking at different ranges. As far as urothelial cancer, we just stuck to the ten mutations per megabase for now.   Dr. Rafeh Naqash: Of course. And one of the other interesting things I really like to see in the paper is your figure specifically on the ECOG performance status and how clinical trials sometimes do not include patients on the higher ECOG performance status spectrum. And your study obviously had a good representation on that standpoint. What were some of the findings from the ECOG standpoint that were somewhat different in your cohort than what you would see in clinical trials in general?   Dr. Shilpa Gupta: Yes, as we've shown in Figure 5, the ECOG in real world, it was quite an eye opener to see that there was a considerable number of patients who were documented as ECOG performance status three. And if you see the ECOG performance status two bar was around 50% and ECOG performance status one was also lower than what has traditionally been included in the phase three trials. And in the phase three trials, there's hardly any patients with ECOG performance status two compared to what we saw in the real world. And very few patients, in fact, hardly any had ECOG performance status zero in our real world analysis. So clearly the trials need to be more inclusive, as has been the ASCO message all along. And it's always very surprising to see the big gap between the real world and the clinical trial patient population.   Dr. Rafeh Naqash: Definitely, I think more and more, especially cooperative group trials that you and many others are leading, are trying to be as inclusive as possible, which is important to get a better understanding of how these therapies do in different patient populations. And one of the questions I wanted to ask you, and I've seen this a few times in different checkpoint therapy treated tumors, is this initial rapid progression in some patients where the chemotherapy arm does better, but the immunotherapy arm kind of falls rapidly and then starts plateauing. In your clinical experience, have you seen that? And if yes, what are the features of some of those patients that have this rapid progression from a clinical and both from a biomarker standpoint?   Dr. Shilpa Gupta: That's a great question, Rafeh, and we do see that every now and then, and especially in my experience, we've seen that in women in particular who have bone metastases are really challenging to treat with immunotherapy. And sometimes we find that the disease just rapidly blows through immunotherapy and we really need to do more biomarker work to understand what determines these biomarkers of hyper-progression, so to speak. I know there's a lot of work going on in the field and we are also trying to understand these by serially collecting blood and circulating tumor DNA from our patients during their treatment journey.   Dr. Rafeh Naqash: Exactly. Definitely work in progress and another unique patient population where more needs to be done to understand what are the events that lead to these hyper-progression aspects, whether it's in the bone or brain or any other compartment in the body.   Well, this has been exciting and interesting, but before we end, we try to know a little bit more about the investigator, the author. So, Shilpa, can you tell us a little bit about your journey in oncology and your journey as a trainee, your journey as faculty, as a clinical trialist, as a successful clinical trialist? And any advice for junior investigators listening to this conversation?   Dr. Shilpa Gupta: Yeah, thank you for asking. I think oncology always struck me as a very exciting field back in my residency days, 2005, 2006. And at the time, so much was going on, like just drugs like bevasizumab were just coming around for colorectal cancer and in lung cancer drugs like EGFR inhibitors were coming around. And that kind of really excited me. And talking with my mentor at the time, who was a really well-renowned transplanter, he said to me that if he had to do it all over again, he would love to get into solid tumor oncology with all the excitement that's going on. I was drawn to oncology also because of, not only it's a learning experience every day, but it can be very gratifying to see amazing responses and patients living longer despite having advanced disease, and also provides a lot of challenges every day when every patient is not the same. So I think that was the reason why I was drawn to oncology and provides us an opportunity to really develop new therapies as opposed to some of the other specialties because of how challenging the patient population is.   And as far as my journey, you know, I've now been in the US for almost 18 years and have been in a variety of places, and I think it's been a very rewarding journey despite multiple bumps along the way. And I'm really glad to be doing what I'm doing and trying to advance the field, clinical trials, and learning from people around me.   Dr. Rafeh Naqash: Thank you so much for giving us a little glimpse into your journey and your experiences. And it's always inspiring to listen to successful investigators and also try to emulate in some ways what you have done and what you've achieved. And thank you again for coming on this podcast. And thank you for choosing JCO Precision Oncology as a destination for your manuscript, and hopefully we'll see more of the same from you and your group in the subsequent years to come and more in this field of biomarkers.   Thank you for listening to JCO Precision Oncology Conversations. You can find all our shows, including this one, at ASCO.org/podcasts or wherever you get your podcasts. To stay up to date, be sure to follow and share JCO PO content on Twitter @JCOPO_ASCO. All JCO PO articles and series can be found at ascopubs.org/journal/PO.     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. 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.     Guest Bio Shilpa Gupta, MD, is Associate Professor of Medicine at the Cleveland Clinic and GU Medical Oncology Director.   Guest disclosures Stock and Other Ownership Interests: Nektar, Moderna Therapeutics Honoraria: Bristol Myers Squibb Consulting or Advisory Role: Gilead Sciences, Guardant Health, AVEO, EMD Serono, Pfizer, Merck, Loxo/Lilly Speakers' Bureau: Bristol Myers Squib

Nizar Tannir describes this randomised phase 3 study presented at ESMO. 

Mohamed Allaf describes the results of this study from ESMO. 

Results from VESPER are now published, so we revisit neoadjuvant ddMVAC and its place as SOC in bladder cancer. Nivolumab nets a new approval with chemo for neoadjuvant treatment of NSCLC. A new CAR-T product is approved for multiple myeloma.