Pembrolizumab Plus Lenvatinib for Previously Untreated Advanced Non–Clear Cell Renal Cell Carcinoma: 3-Year Follow-Up of the Phase 2 KEYNOTE-B61 Study
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.
