期刊
NEW ENGLAND JOURNAL OF MEDICINE
卷 378, 期 14, 页码 1277-1290出版社
MASSACHUSETTS MEDICAL SOC
DOI: 10.1056/NEJMoa1712126
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资金
- Bristol-Myers Squibb
- Ono Pharmaceutical
- Memorial Sloan Kettering Cancer Center [P30 CA008748]
- Pfizer
- Novartis
- Eisai
- Exelixis
- Genentech/Roche
- Epizyme
- Mirati Therapeutics
- Argos Therapeutics
- Nektar
- Oncorena
- Merck
- Array BioPharma
- Genentech BioOncology
- Prometheus Laboratories
- Merck Sharp Dohme
- Astellas Pharma
- Bayer
- AstraZeneca
- Genentech
- Peloton Therapeutics
- Tracon Pharmaceuticals
- Cerulean Pharma
- Foundation Medicine
- GlaxoSmithKline
- Corvus Pharmaceuticals
- Acceleron Pharma
- Aveo Pharmaceuticals
- Dendreon
- Eli Lilly
- Clovis Oncology
- Horizon Pharma
- Inovio Pharmaceuticals
- SynerGene Therapeutics
- Ipsen
- Sanofi
- EUSA Pharma
- Janssen
- Celldex Therapeutics
- Bayer HealthCare
- Hexal
- Apogepha
- Intuitive Surgical
- Sanofi-Aventis
- Amgen
- MedUpdate
- Novartger Ingelheim
- Taiho Pharmaceutical
- Mylan
- Merrimack Pharmaceuticals
- AbbVie
- BioMarin Pharmaceutical
- Daiichi Sankyo
- Abraxis BioScience
- Asana BioSciences
- AB Science
- Mediis
- Boehrinvation
- ImClone
- LEO Pharma
- Millennium Pharmaceuticals
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.
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