Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer

作者：Charles S. Fuchs, Toshihiko Doi, Raymond Woo-Jun Jang, Kei Muro, Taroh Satoh, Manuela Machado, Weijing Sun, Shadia Ibrahim Jalal, Manish A. Shah, Jean-Phillipe Metges, Marcelo Garrido, Talia Golan, Mario Mandalà, Zev A. Wainberg, Daniel V.T. Catenacci, Atsushi Ohtsu, Kohei Shitara, Ravit Geva, Jonathan Scott Bleeker, Andrew H. Ko, Geoffrey Yuyat Ku, Philip Philip, Peter C. Enzinger, Yung‐Jue Bang, Diane J. Levitan, Jiangdian Wang, Minori Koshiji Rosales, Rita P. Dalal, Harry H. Yoon · 发表于：JAMA Oncology · 年份：2018 · DOI：10.1001/jamaoncol.2018.0013 · 被引用次数：1837 · 研究领域：Gastric Cancer Management and Outcomes、Cancer Immunotherapy and Biomarkers、Esophageal Cancer Research and Treatment

Importance: Therapeutic options are needed for patients with advanced gastric cancer whose disease has progressed after 2 or more lines of therapy. Objective: To evaluate the safety and efficacy of pembrolizumab in a cohort of patients with previously treated gastric or gastroesophageal junction cancer. Design, Setting, and Participants: In the phase 2, global, open-label, single-arm, multicohort KEYNOTE-059 study, 259 patients in 16 countries were enrolled in a cohort between March 2, 2015, and May 26, 2016. Median (range) follow-up was 5.8 (0.5-21.6) months. Intervention: Patients received pembrolizumab, 200 mg, intravenously every 3 weeks until disease progression, investigator or patient decision to withdraw, or unacceptable toxic effects. Main Outcomes and Measures: Primary end points were objective response rate and safety. Objective response rate was assessed by central radiologic review per Response Evaluation Criteria in Solid Tumors, version 1.1, in all patients and those with programmed cell death 1 ligand 1 (PD-L1)-positive tumors. Expression of PD-L1 was assessed by immunohistochemistry. Secondary end points included response duration. Results: Of 259 patients enrolled, most were male (198 [76.4%]) and white (200 [77.2%]); median (range) age was 62 (24-89) years. Objective response rate was 11.6% (95% CI, 8.0%-16.1%; 30 of 259 patients), with complete response in 2.3% (95% CI, 0.9%-5.0%; 6 of 259 patients). Median (range) response duration was 8.4 (1.6+ to 17.3+)...