Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer
Authors: Jianming Xu, Haiping Jiang, Yueyin Pan, Kangsheng Gu, Shundong Cang, Lei Han, Yongqian Shu, Jiayi Li, Junhui Zhao, Hongming Pan, Suxia Luo, Yanru Qin, Qunyi Guo, Yuxian Bai, Yang Ling, Jianwei Yang, Zhilong Yan, Lei Yang, Yong Tang, Yifu He, Liangming Zhang, Xinjun Liang, Zuoxing Niu, Jingdong Zhang, Yong Mao, Yingmei Guo, Bo Peng, Ziran Li, Ying Liu, Yan Wang, Hui Zhou, Hongmei Sun, Qi Wang, Junhe Li, Da Jiang, Weijian Guo, Jieer Ying, Shubin Wang, Aimin Zang, Shirong Cai, Chunhong Hu, Tao Zhang, Min Tao, Jun Liang, Qinsheng Mao, Minghui Zhang, Rui Mao, Hui Yang, Hongyu Zhang, Lin Shen, Jin Lu, Wenxin Li, Yamin Chen, Lei Chen, Zhixiang Zhuang, Chunmei Bai, Heli Liu, Jingtang Chen, Wangjun Liao, Meng Qiu, Rongfeng Song, Man Li, Suying Qian, Yunpeng Liu, Jiang Liu, Dong Wang, Xianli Yin, Zhiming Huang
Journal: JAMA (2023)

Importance Gastric and gastroesophageal junction cancers are diagnosed in more than 1 million people worldwide annually, and few effective treatments are available. Sintilimab, a recombinant human IgG4 monoclonal antibody that binds to programmed cell death 1 (PD-1), in combination with chemotherapy, has demonstrated promising efficacy. Objective To compare overall survival of patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancers who were treated with sintilimab with chemotherapy vs placebo with chemotherapy. Also compared were a subset of patients with a PD ligand 1 (PD-L1) combined positive score (CPS) of 5 or more (range, 1-100). Design, Setting, and Participants Randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 62 hospitals in China that enrolled 650 patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma between January 3, 2019, and August 5, 2020. Final follow-up occurred on June 20, 2021. Interventions Patients were randomized 1:1 to either sintilimab (n = 327) or placebo (n = 323) combined with capecitabine and oxaliplatin (the XELOX regimen) every 3 weeks for a maximum of 6 cycles. Maintenance therapy with sintilimab or placebo plus capecitabine continued for up to 2 years. Main Outcomes and Measures The primary end point was overall survival time from randomization. Results Of the 650 patients (mean age, 59 years; 483 [74.3%] men), 327 were randomized to sintilimab plus chemotherapy and 323 to placebo plus chemotherapy. Among the randomized patients, 397 (61.1%) had tumors with a PD-L1 CPS of 5 or more; 563 (86.6%) discontinued study treatment and 388 (59.7%) died; 1 patient (&amp;amp;lt;0.1%) was lost to follow-up. Among all randomized patients, sintilimab improved overall survival compared with placebo (median, 15.2 vs 12.3 months; stratified hazard ratio [HR], 0.77 [95% CI, 0.63-0.94]; P = .009). Among patients with a CPS of 5 or more, sintilimab improved overall survival compared with placebo (median, 18.4 vs 12.9 months; HR, 0.66 [95% CI, 0.50-0.86]; P = .002). The most common grade 3 or higher treatment-related adverse events were decreased platelet count (sintilimab, 24.7% vs placebo, 21.3%), decreased neutrophil count (sintilimab, 20.1% vs placebo, 18.8%), and anemia (sintilimab, 12.5% vs placebo, 8.8%). Conclusions and Relevance Among patients with unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma treated with first-line chemotherapy, sintilimab significantly improved overall survival for all patients and for patients with a CPS of 5 or more compared with placebo. Trial Registration ClinicalTrials.gov Identifier: NCT03745170