Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer

作者：Kohei Shitara, Eric Van Cutsem, Yung‐Jue Bang, Charles S. Fuchs, Lucjan Wyrwicz, Keun‐Wook Lee, Iveta Kudaba, Marcelo Garrido, Hyun Cheol Chung, Jeeyun Lee, Hugo R. Castro, Wasat Mansoor, Maria Ignez Braghiroli, Nina Karaseva, Christian Caglevic, Luis J. Villanueva-Rivera, Eray Goekkurt, Hironaga Satake, Peter C. Enzinger, María Alsina, Al B. Benson, Joseph Chao, Andrew H. Ko, Zev A. Wainberg, Uma Kher, Sukrut Shah, Soonmo Peter Kang, Josep Tabernero · 发表于：JAMA Oncology · 年份：2020 · DOI：10.1001/jamaoncol.2020.3370 · 被引用次数：1167 · 研究领域：Gastric Cancer Management and Outcomes、Cancer Immunotherapy and Biomarkers、Esophageal Cancer Research and Treatment

Importance: Safe and effective therapies for untreated, advanced gastric/gastroesophageal junction (G/GEJ) cancer remain an unmet need. Objective: To evaluate the antitumor activity of pembrolizumab, pembrolizumab plus chemotherapy, or chemotherapy alone in patients with untreated, advanced G/GEJ cancer with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or greater. Design, Setting, and Participants: The phase 3 KEYNOTE-062 randomized, controlled, partially blinded interventional trial enrolled 763 patients with untreated, locally advanced/unresectable or metastatic G/GEJ cancer with PD-L1 CPS of 1 or greater from 200 centers in 29 countries between September 18, 2015, and May 26, 2017. Interventions: Patients were randomized 1:1:1 to pembrolizumab 200 mg, pembrolizumab plus chemotherapy (cisplatin 80 mg/m2/d on day 1 plus fluorouracil 800 mg/m2/d on days 1 to 5 or capecitabine 1000 mg/m2 twice daily), or chemotherapy plus placebo, every 3 weeks. Main Outcomes and Measures: Primary end points were overall survival (OS) and progression-free survival (PFS) in patients with PD-L1 CPS of 1 or greater or 10 or greater. Results: A total of 763 patients were randomized to pembrolizumab (n = 256), pembrolizumab plus chemotherapy (n = 257), or chemotherapy (n = 250). The median (range) age of all patients in the study cohort was 62 (20-87) years; 554 of 763 (72.6%) were men. At final analysis, after a median (range) follow-up of 29.4 (22.0-41.3) months, pemb...