Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer

作者：Leena Gandhi, Delvys Rodríguez‐Abreu, Shirish M. Gadgeel, Emilio Esteban, Enriqueta Felip, Flávia De Angelis, Manuel Dómine, Philip R. Clingan, Maximilian J. Hochmair, Steven Powell, Susanna Y. Cheng, Helge Bischoff, Nir Peled, Francesco Grossi, Ross Jennens, Martin Reck, Rina Hui, Edward B. Garon, Michael Boyer, Belén Rubio‐Viqueira, Silvia Novello, Takayasu Kurata, Jhanelle E. Gray, John Vida, Ziwen Wei, Jing Yang, Harry Raftopoulos, M. Catherine Pietanza, Marina Chiara Garassino · 发表于：New England Journal of Medicine · 年份：2018 · DOI：10.1056/nejmoa1801005 · 被引用次数：6703 · 研究领域：Cancer Immunotherapy and Biomarkers、Lung Cancer Diagnosis and Treatment、Lung Cancer Treatments and Mutations

BACKGROUND: First-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial. METHODS: In this double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK mutations who had received no previous treatment for metastatic disease to receive pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy. Crossover to pembrolizumab monotherapy was permitted among the patients in the placebo-combination group who had verified disease progression. The primary end points were overall survival and progression-free survival, as assessed by blinded, independent central radiologic review. RESULTS: After a median follow-up of 10.5 months, the estimated rate of overall survival at 12 months was 69.2% (95% confidence interval [CI], 64.1 to 73.8) in the pembrolizumab-combination group versus 49.4% (95% CI, 42.1 to 56.2) in the plac...