Treatment Considerations in Non-Clear Cell Renal Cell Carcinom

Dr. Voss and Dr. Serzan turn to non-clear cell renal cell carcinoma (RCC), highlighting the heterogeneity of these tumors and the ongoing unmet need for more effective treatment strategies. Dr. Serzan discusses how advances in molecular characterization, including somatic and germline testing, have provided greater insight into distinct non-clear cell subtypes, including papillary, chromophobe, translocation, unclassified, and molecularly defined RCC. He reviews contemporary phase 2 evidence evaluating IO-TKI combinations in these populations, focusing on the cabozantinib plus nivolumab study and the KEYNOTE-B61 study of lenvatinib plus pembrolizumab. Dr. Serzan highlights the final analysis of the cabozantinib plus nivolumab study presented at ASCO 2026, including encouraging activity across several non-clear cell subtypes and particularly notable responses among patients with FH-deficient RCC. In contrast, no objective responses were observed among the small chromophobe RCC cohort, although most patients achieved stable disease. Dr. Voss notes the tumor shrinkage observed in chromophobe RCC while emphasizing differences in activity across non-clear cell subtypes.