First-line cabozantinib plus nivolumab and ipilimumab for intermediate or poor risk advanced renal cell carcinoma

Cabozantinib plus nivolumab (C+N) and nivolumab plus ipilimumab (N+I) are both standard of care for first-line advanced renal cell carcinoma (aRCC). The multinational phase 3 COSMIC-313 trial evaluates C+N+I versus placebo (P)+N+I for previously untreated intermediate (75% of patients) or poor risk (25%) clear cell aRCC. The primary endpoint was progression-free survival by blinded independent radiology review. This endpoint was met with median PFS not reached with C+N+I versus 11.3 months with P+N+I (HR 0.73; p=0.013). Grade 3 or 4 treatment-related adverse events occurred in 73% with C+N+I versus 41% with P+N+I. Grade 5 TRAEs occurred in 1% in each arm, and TRAEs leading to discontinuation in 12% versus 5%. The authors conclude that C+N+I significantly improved PFS versus P+N+I in previously untreated intermediate or poor risk aRCC. Safety was consistent with known profiles of the treatment components. Follow-up for OS is ongoing.