Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

作者：Martin Reck, Delvys Rodríguez‐Abreu, Andrew Robinson, Rina Hui, Tibor Csőszi, Andrea Fülöp, Maya Gottfried, Nir Peled, Ali Tafreshi, Sinéad Cuffe, Mary O’Brien, Suman Rao, Katsuyuki Hotta, Melanie A. Leiby, Gregory M. Lubiniecki, Yue Shentu, Reshma Rangwala, Julie R. Brahmer · 发表于：New England Journal of Medicine · 年份：2016 · DOI：10.1056/nejmoa1606774 · 被引用次数：10265 · 研究领域：Cancer Immunotherapy and Biomarkers、Lung Cancer Diagnosis and Treatment、Peptidase Inhibition and Analysis

BACKGROUND: Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1). METHODS: In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety. RESULTS: Median progression-free survival was 10.3 months (95% confidence interval [CI], 6.7 to not reached) in the pembrolizumab group versus 6.0 months (95% CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6 months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy group (hazard ratio for death, 0.60; 95% CI, 0.41 to 0.89; P=0.005). The respon...