The Absolute Effect / Renal Cell Carcinoma / Medical
In previously treated advanced clear-cell RCC, does nivolumab improve survival compared with everolimus?
821 patients with advanced clear-cell RCC previously treated with one or two antiangiogenic regimens; randomized open-label phase III trial.
Nivolumab 3 mg/kg IV every 2 weeks versus everolimus 10 mg orally once daily.
Median overall survival was 25.0 vs 19.6 months; HR for death 0.73 (98.5% CI 0.57–0.93), p=0.002. Investigator-assessed objective response was 25% vs 5%, an absolute increase of 20 percentage points (NNT ≈ 5 for one additional response; response is not a survival endpoint).
Median PFS was 4.6 vs 4.4 months, HR 0.88 (95% CI 0.75–1.03), p=0.11.
Grade 3–4 treatment-related adverse events occurred in 19% with nivolumab versus 37% with everolimus: absolute reduction 18 points. Treatment-specific immune toxicities require separate clinical consideration.
CheckMate 025 established a survival benefit for PD-1 blockade over everolimus despite little difference in median PFS, illustrating why OS and response should not be inferred from PFS alone.
CheckMate 025 established nivolumab over everolimus after prior antiangiogenic therapy in advanced clear-cell RCC. Its role is now interpreted within a treatment landscape transformed by first-line immune-checkpoint inhibitor combinations; it is not a direct comparison against current first-line IO–TKI regimens or evidence for ICI rechallenge after progression on prior ICI. Subsequent therapy should be chosen according to previous ICI/TKI exposure, disease tempo, IMDC risk, comorbidity and current guidance.
CheckMate 025 primary report ↗ · EAU RCC disease-management guidance ↗