Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

作者：Robert J. Motzer, Bernard Escudier, Ray McDermott, Saby George, Hans J. Hammers, Sandhya Srinivas, Scott S. Tykodi, Jeffrey A. Sosman, Giuseppe Procopio, Elizabeth R. Plimack, Daniel Castellano, Toni K. Choueiri, Howard Gurney, Frede Donskov, Petri Bono, John Wagstaff, Thomas Gauler, Takeshi Ueda, Yoshihiko Tomita, Fabio A.B. Schutz, Christian Kollmannsberger, James Larkin, Alain Ravaud, Jason S. Simon, Li-An Xu, Ian M. Waxman, Padmanee Sharma · 发表于：New England Journal of Medicine · 年份：2015 · DOI：10.1056/nejmoa1510665 · 被引用次数：5954 · 研究领域：Renal cell carcinoma treatment、Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis

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, 0.7...