Emerging Treatment Strategies in Non-Clear Cell Renal Cell Carcinom

Dr. Voss and Dr. Serzan continue their discussion of treatment strategies for non-clear cell renal cell carcinoma (RCC), focusing on evidence for IO-TKI and IO-IO approaches across different histologic subtypes. Dr. Serzan reviews KEYNOTE-B61, highlighting the activity observed with lenvatinib plus pembrolizumab across papillary, chromophobe, and unclassified RCC. Dr. Voss notes that although these phase 2 data are encouraging, interpretation is limited by relatively small patient populations and the absence of randomized comparisons in these studies. The experts discuss how response patterns across several non-clear cell subtypes appear encouraging relative to historical TKI monotherapy, while chromophobe RCC may demonstrate less sensitivity to immune checkpoint inhibitor-based approaches. Dr. Voss then reviews the randomized phase 2 SUNNIFORECAST trial evaluating ipilimumab plus nivolumab versus standard-of-care therapy in previously untreated non-clear cell RCC. The discussion also highlights emerging data in FH-deficient RCC, including reports of substantial activity with TKI-IO combinations, underscoring the growing importance of molecular characterization when considering treatment strategies for these less common RCC subtypes.