BACKGROUND: Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was 
associated with encouraging overall survival in uncontrolled studies involving 
previously treated patients with advanced renal-cell carcinoma. This randomized, 
open-label, phase 3 study compared nivolumab with everolimus in patients with 
renal-cell carcinoma who had received previous treatment.
METHODS: A total of 821 patients with advanced clear-cell renal-cell carcinoma 
for which they had received previous treatment with one or two regimens of 
antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg 
of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg 
everolimus tablet orally once daily. The primary end point was overall survival. 
The secondary end points included the objective response rate and safety.
RESULTS: The median overall survival was 25.0 months (95% confidence interval 
[CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 
23.1) with everolimus. The hazard ratio for death with nivolumab versus 
everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.002), which met the 
prespecified criterion for superiority (P≤0.0148). The objective response rate 
was greater with nivolumab than with everolimus (25% vs. 5%; odds ratio, 5.98 
[95% CI, 3.68 to 9.72]; P<0.001). The median progression-free survival was 4.6 
months (95% CI, 3.7 to 5.4) with nivolumab and 4.4 months (95% CI, 3.7 to 5.5) 
with everolimus (hazard ratio, 0.88; 95% CI, 0.75 to 1.03; P=0.11). Grade 3 or 4 
treatment-related adverse events occurred in 19% of the patients receiving 
nivolumab and in 37% of the patients receiving everolimus; the most common event 
with nivolumab was fatigue (in 2% of the patients), and the most common event 
with everolimus was anemia (in 8%).
CONCLUSIONS: Among patients with previously treated advanced renal-cell 
carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events 
occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; 
CheckMate 025 ClinicalTrials.gov number, NCT01668784.).