Pembrolizumab versus Ipilimumab in Advanced Melanoma

作者：Caroline Robert, Jacob Schachter, Georgina V. Long, Ana Arance, Jean‐Jacques Grob, Laurent Mortier, Adil Daud, Matteo S. Carlino, Catriona M. McNeil, Michal Lotem, James Larkin, Paul Lorigan, Bart Neyns, Christian U. Blank, Omid Hamid, Christine Mateus, Ronnie Shapira‐Frommer, Michele Kosh, Honghong Zhou, Nageatte Ibrahim, Scot Ebbinghaus, Antoni Ribas · 发表于：New England Journal of Medicine · 年份：2015 · DOI：10.1056/nejmoa1503093 · 被引用次数：5938 · 研究领域：Cancer Immunotherapy and Biomarkers、Cutaneous Melanoma Detection and Management、Melanoma and MAPK Pathways

BACKGROUND: The immune checkpoint inhibitor ipilimumab is the standard-of-care treatment for patients with advanced melanoma. Pembrolizumab inhibits the programmed cell death 1 (PD-1) immune checkpoint and has antitumor activity in patients with advanced melanoma. METHODS: In this randomized, controlled, phase 3 study, we assigned 834 patients with advanced melanoma in a 1:1:1 ratio to receive pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks or four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks. Primary end points were progression-free and overall survival. RESULTS: The estimated 6-month progression-free-survival rates were 47.3% for pembrolizumab every 2 weeks, 46.4% for pembrolizumab every 3 weeks, and 26.5% for ipilimumab (hazard ratio for disease progression, 0.58; P<0.001 for both pembrolizumab regimens versus ipilimumab; 95% confidence intervals [CIs], 0.46 to 0.72 and 0.47 to 0.72, respectively). Estimated 12-month survival rates were 74.1%, 68.4%, and 58.2%, respectively (hazard ratio for death for pembrolizumab every 2 weeks, 0.63; 95% CI, 0.47 to 0.83; P=0.0005; hazard ratio for pembrolizumab every 3 weeks, 0.69; 95% CI, 0.52 to 0.90; P=0.0036). The response rate was improved with pembrolizumab administered every 2 weeks (33.7%) and every 3 weeks (32.9%), as compared with ipilimumab (11.9%) (P<0.001 for both comparisons). Responses were ongoing in 89.4%, 96.7%, and 87.9% of patients, respectively, after a media...