BACKGROUND: Nivolumab plus ipilimumab produced objective responses in patients 
with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared 
nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell 
advanced renal-cell carcinoma.
METHODS: We randomly assigned adults in a 1:1 ratio to receive either nivolumab 
(3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) 
intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per 
kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks 
(6-week cycle). The coprimary end points were overall survival (alpha level, 
0.04), objective response rate (alpha level, 0.001), and progression-free 
survival (alpha level, 0.009) among patients with intermediate or poor 
prognostic risk.
RESULTS: A total of 1096 patients were assigned to receive nivolumab plus 
ipilimumab (550 patients) or sunitinib (546 patients); 425 and 422, 
respectively, had intermediate or poor risk. At a median follow-up of 25.2 
months in intermediate- and poor-risk patients, the 18-month overall survival 
rate was 75% (95% confidence interval [CI], 70 to 78) with nivolumab plus 
ipilimumab and 60% (95% CI, 55 to 65) with sunitinib; the median overall 
survival was not reached with nivolumab plus ipilimumab versus 26.0 months with 
sunitinib (hazard ratio for death, 0.63; P<0.001). The objective response rate 
was 42% versus 27% (P<0.001), and the complete response rate was 9% versus 1%. 
The median progression-free survival was 11.6 months and 8.4 months, 
respectively (hazard ratio for disease progression or death, 0.82; P=0.03, not 
significant per the prespecified 0.009 threshold). Treatment-related adverse 
events occurred in 509 of 547 patients (93%) in the nivolumab-plus-ipilimumab 
group and 521 of 535 patients (97%) in the sunitinib group; grade 3 or 4 events 
occurred in 250 patients (46%) and 335 patients (63%), respectively. 
Treatment-related adverse events leading to discontinuation occurred in 22% and 
12% of the patients in the respective groups.
CONCLUSIONS: Overall survival and objective response rates were significantly 
higher with nivolumab plus ipilimumab than with sunitinib among intermediate- 
and poor-risk patients with previously untreated advanced renal-cell carcinoma. 
(Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 214 
ClinicalTrials.gov number, NCT02231749 .).