Nivolumab in Combination With Platinum‐Based Doublet Chemotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer

作者：Naiyer A. Rizvi, Matthew D. Hellmann, Julie R. Brahmer, Rosalyn A. Juergens, Hossein Borghaei, Scott Gettinger, Laura Q.M. Chow, David E. Gerber, Scott A. Laurie, Jonathan W. Goldman, Frances A. Shepherd, Allen C. Chen, Yun Shen, Faith E. Nathan, Christopher Harbison, Scott Antonia · 发表于：Journal of Clinical Oncology · 年份：2016 · DOI：10.1200/jco.2016.66.9861 · 被引用次数：450 · 研究领域：Cancer Immunotherapy and Biomarkers、Lung Cancer Treatments and Mutations、Lung Cancer Research Studies

PURPOSE: Nivolumab, a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody, has demonstrated improved survival in previously treated patients with advanced non-small-cell lung cancer (NSCLC). CheckMate 012, a phase I, multicohort study, was conducted to explore the safety and efficacy of nivolumab as monotherapy or combined with current standard therapies in first-line advanced NSCLC. Here, we report results for nivolumab plus platinum-based doublet chemotherapy (PT-DC). PATIENTS AND METHODS: Patients (N = 56) received nivolumab (intravenously) plus PT-DC concurrently every 3 weeks for four cycles followed by nivolumab alone until progression or unacceptable toxicity. Regimens were nivolumab 10 mg/kg plus gemcitabine-cisplatin (squamous) or pemetrexed-cisplatin (nonsquamous) or nivolumab 5 or 10 mg/kg plus paclitaxel-carboplatin (all histologies). The primary objective was to assess safety and tolerability. Secondary objectives included objective response rate and 24-week progression-free survival rate (per Response Evaluation Criteria in Solid Tumors version 1.1); exploratory objectives included overall survival (OS) and response by tumor programmed death ligand-1 expression. RESULTS: No dose-limiting toxicities occurred during the first 6 weeks of treatment. Forty-five percent of patients (25 of 56 patients) reported grade 3 or 4 treatment-related adverse events (AEs); 7% of patients (n = 4) had pneumonitis. Twenty-one percent of patients (n...