Nivolumab in Previously Untreated Melanoma without BRAF Mutation

作者：Caroline Robert, Georgina V. Long, Benjamin Brady, Caroline Dutriaux, Michele Maio, Laurent Mortier, Jessica C. Hassel, Piotr Rutkowski, Catriona M. McNeil, Ewa Kalinka‐Warzocha, Kerry J. Savage, Micaela Hernberg, Célèste Lebbé, J. Charles, Catalin Mihalcioiu, Vanna Chiarion‐Sileni, Cornelia Mauch, Francesco Cognetti, Ana Arance, Henrik Schmidt, Dirk Schadendorf, Helen Gogas, L. Lundgren-Eriksson, Christine E. Horak, Brian J. Sharkey, Ian M. Waxman, Victoria Atkinson, Paolo A. Ascierto · 发表于：New England Journal of Medicine · 年份：2014 · DOI：10.1056/nejmoa1412082 · 被引用次数：5397 · 研究领域：Melanoma and MAPK Pathways、Cancer Immunotherapy and Biomarkers、Cutaneous Melanoma Detection and Management

BACKGROUND: Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma. The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study. METHODS: We randomly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab (at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazine-matched placebo every 3 weeks) or dacarbazine (at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks). The primary end point was overall survival. RESULTS: At 1 year, the overall rate of survival was 72.9% (95% confidence interval [CI], 65.5 to 78.9) in the nivolumab group, as compared with 42.1% (95% CI, 33.0 to 50.9) in the dacarbazine group (hazard ratio for death, 0.42; 99.79% CI, 0.25 to 0.73; P<0.001). The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group (hazard ratio for death or progression of disease, 0.43; 95% CI, 0.34 to 0.56; P<0.001). The objective response rate was 40.0% (95% CI, 33.3 to 47.0) in the nivolumab group versus 13.9% (95% CI, 9.5 to 19.4) in the dacarbazine group (odds ratio, 4.06; P<0.001). The survival benefit with nivolumab versus dacarbazine was observed across prespecified subgroups, including subgroups def...