Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma

作者：James Larkin, Vanna Chiarion‐Sileni, René González, Jean‐Jacques Grob, C. Lance Cowey, Christopher D. Lao, Dirk Schadendorf, Reinhard Dummer, Michael Smylie, Piotr Rutkowski, Pier Francesco Ferrucci, Andrew Hill, John Wagstaff, Matteo S. Carlino, John B.A.G. Haanen, Michele Maio, Iván Márquez‐Rodas, Grant A. McArthur, Paolo A. Ascierto, Georgina V. Long, Margaret K. Callahan, Michael A. Postow, Kenneth F. Grossmann, Mario Sznol, Brigitte Dréno, Lars Bastholt, Arvin Yang, Linda M. Rollin, Christine E. Horak, F. Stephen Hodi, Jedd D. Wolchok · 发表于：New England Journal of Medicine · 年份：2015 · DOI：10.1056/nejmoa1504030 · 被引用次数：8241 · 研究领域：Cancer Immunotherapy and Biomarkers、Melanoma and MAPK Pathways、Immunotherapy and Immune Responses

BACKGROUND: Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma. METHODS: We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone. Progression-free survival and overall survival were coprimary end points. Results regarding progression-free survival are presented here. RESULTS: The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1-negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8...