Cabozantinib plus nivolumab and ipilimumab in previously untreated, advanced renal cell carcinoma: final results and biomarker analyses from the phase III COSMIC-313 study.
Summary
The phase III COSMIC-313 study investigated the addition of cabozantinib to nivolumab and ipilimumab in previously untreated patients with advanced renal cell carcinoma. Final results confirmed a significant progression-free survival (PFS) benefit for the triplet regimen (16.6 months vs 11.2 months for the doublet). However, no significant improvement in overall survival (OS) was observed. Exploratory biomarker analyses suggest that patients with higher levels of M2-like macrophages might experience improved PFS and OS with the triplet therapy.
Analysis
Clinique: This phase III study demonstrates a progression-free survival benefit (HR 0.82) with the addition of cabozantinib to nivolumab and ipilimumab for advanced renal cell carcinoma. However, the lack of overall survival benefit is a critical point that limits immediate clinical impact on standard treatment guidelines. The safety profile is manageable but with higher grade 3/4 toxicity for the triplet regimen (75% vs 43%). The discovery of a potential predictive biomarker, M2-like macrophages, could justify future clinical trials to validate this personalized approach, with a potential clinical impact in 3-5 years if validated.