Panelists discuss how the 3-year follow-up data from the KEYNOTE-B61 study demonstrate that pembrolizumab plus lenvatinib represents a new standard of care for advanced non–clear cell renal cell carcinoma (RCC), achieving impressive response rates of approximately 51%, median progression-free survival of 17.9 months, and median overall survival of 41.5 months across various histological subtypes, including papillary, chromophobe, translocation, and unclassified RCC.
EP. 1: Introducing KEYNOTE-B61 in Non–Clear Cell RCC
September 12th 2025Panelists discuss how they will review the KEYNOTE-B61 phase 2 study examining pembrolizumab plus lenvatinib for previously untreated advanced non–clear cell renal cell carcinoma (RCC), including an overview of non–clear cell RCC and integration of the 3-year follow-up data into clinical practice.
EP. 2: Challenges in Treating Non–Clear Cell RCC
September 12th 2025Panelists discuss how non–clear cell renal cell carcinoma (RCC) represents a challenging, heterogeneous collection of rare tumors comprising 25% to 30% of all RCC cases, requiring careful histological review and individualized risk stratification based on tumor biology, disease tempo, and burden rather than traditional treatment algorithms used for clear cell RCC.
EP. 3: Study Design and Patient Population
September 19th 2025Panelists discuss how the KEYNOTE-B61 phase 2 single-arm study represents the largest prospective trial evaluating pembrolizumab plus lenvatinib as first-line treatment for advanced non–clear cell renal cell carcinoma (RCC), enrolling 158 patients across all major histological subtypes with an impressive median follow-up of 41.6 months and updated 3-year survival data.
EP. 4: Representativeness of Histologies in Clinical Practice
September 19th 2025Panelists discuss how the KEYNOTE-B61 study population truly represents real-world clinical practice, with papillary renal cell carcinoma (RCC) being the most common subtype followed by chromophobe, unclassified, and translocation RCC as the top 4 subtypes typically encountered in clinic, while rarer variants comprise only 2% to 3% of non–clear cell cases.
EP. 5: Efficacy Findings: Response and Disease Control Rates
September 26th 2025Panelists discuss how the KEYNOTE-B61 study demonstrated remarkable efficacy with a 50.6% objective response rate and 82% disease control rate across all non–clear cell renal cell carcinoma (RCC) histologies, representing a significant improvement over historical tyrosine kinase inhibitor (TKI) data that showed response rates below 30% and setting a new treatment benchmark for this patient population.
EP. 6: Durability of Response and Histology-Specific Insights
September 26th 2025Panelists discuss how the durability of response data was particularly compelling, with a median duration of response of approximately 2 years and 35% of patients maintaining responses at 3 years, especially noting the surprising 31% response rate in chromophobe renal cell carcinoma (RCC) despite this histology's historically poor responsiveness to immunotherapy due to low tumor mutational burden.
EP. 7: Progression-Free and Overall Survival Outcomes
October 3rd 2025Panelists discuss how the KEYNOTE-B61 study demonstrated impressive survival outcomes with a median progression-free survival (PFS) of 17.9 months and median overall survival (OS) of 41.5 months, effectively doubling the historical tyrosine kinase inhibitor (TKI) monotherapy benchmarks of 8 to 9 months PFS and 21 months OS in patients with non–clear cell renal cell carcinoma (RCC).
EP. 8: Managing Safety and Adverse Events in Practice
October 3rd 2025Panelists discuss how managing the safety profile of pembrolizumab plus lenvatinib requires proactive patient education and early toxicity identification, with approximately 25% of patients discontinuing therapy due to adverse events in both clinical trials and real-world practice, emphasizing the importance of distinguishing between tyrosine kinase inhibitor (TKI) and immunotherapy-related adverse events for appropriate management.
EP. 9: Clinical Implications and Future Directions
October 10th 2025Panelists discuss how pembrolizumab plus lenvatinib has established a new benchmark and become the preferred first-line treatment option for more than 95% of patients with non–clear cell renal cell carcinoma (RCC), according to national guidelines, demonstrating activity across all major histological subtypes despite the heterogeneous nature of these diseases, while acknowledging that specific rare histologies may still require tailored approaches.