First-line cabozantanib plus nivolumab and ipilimumab for advanced renal cell carcinoma: final results of COSMIC-313

Primary results from the multinational phase 3 COSMIC-313 trial demonstrated significantly longer progression-free survival (PFS) with first-line cabozantinib plus nivolumab and ipilimumab (triplet group) versus placebo plus nivolumab and ipilimumab (doublet group) among patients with advanced renal cell carcinoma (aRCC). Final results of the trial have now been published. After a median follow-up of 45.0 months, the updated median PFS in the triplet group was 16.6 months, compared with 11.2 months in the doublet group (HR 0.82; 95% CI 0.69-0.98) whereas there was no significant difference in overall survival (1.02; 0.85-1.23) and the safety profilewas consistent with the earlier analysis (grade 3-4 treatment-related adverse events in 75% versus 43%). Among patients with higher levels of M2-like macrophagesm the triplet regimen was associated with significantly improved PFS and OS compared with the doublet regimen. Responders in the triplet group exhibited elevated angiogenic signatures and reduced immune-related pathways, while responders in the doublet group had robust immune activation. The authors conclude that with longer follow-up, addition of cabozantinib to first-line nivolumab and ipilimumab continues to demonstrate a PFS benefit among patients with aRCC.