Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer – The ORIENT-16 Randomized Clinical Trial

Author(s): Jianming Xu, MD1; Haiping Jiang, MD2; Yueyin Pan, PhD3; Kangsheng Gu, MD4; Shundong Cang, MD5; Lei Han, MM6; Yongqian Shu, MD7; Jiayi Li, MM8; Junhui Zhao, MM9; Hongming Pan, MD10; Suxia Luo, MD11; Yanru Qin, MD12; Qunyi Guo, MM13; Yuxian Bai, MD14; Yang Ling, MD15; Jianwei Yang, MB16; Zhilong Yan, MM17; Lei Yang, MD18; Yong Tang, MM19; Yifu He, MD20; Liangming Zhang, MD21; Xinjun Liang, MD22; Zuoxing Niu, MM23; Jingdong Zhang, MD24; Yong Mao, MD25; Yingmei Guo, MSc26; Bo Peng, PhD26; Ziran Li, MD26; Ying Liu, MD26; Yan Wang, MD26; Hui Zhou, MD26; for the ORIENT-16 Investigators
Source: JAMA. 2023;330(21):2064-2074. doi:10.1001/jama.2023.19918
Maem Hussein MD

Dr. Maen Hussein's Thoughts

A different PD-1 inhibitor improves survival in patients with unresectable gastric of GEJ tumors, CPS >5, they also had maintenance capecitabine.

Confirming role for maintenance immunotherapy.


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.


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).


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.


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.


The primary end point was overall survival time from randomization.


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 (<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%).


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.

Author Affiliations

1The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China; 2The First Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China; 3Anhui Provincial Hospital, Hefei, China; 4The First Affiliated Hospital of Anhui Medical University, Hefei, China; 5Henan Provincial People’s Hospital, Zhengzhou, China; 6Affiliated Hospital of Jining Medical University, Jining, China; 7Jiangsu Provincial Hospital, Nanjing, China; 8The First Affiliated Hospital of Xiamen University, Xiamen, China; 9Qinghai University Affiliated Hospital, Xining, China; 10Sir Run Run Shaw Hospital School of Medicine, Zhejiang University, Hangzhou, China; 11Henan Cancer Hospital, Zhengzhou, China; 12The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; 13Taizhou Hospital of Zhejiang Province, Linhai, China; 14Harbin Medical University Cancer Hospital, Harbin, China; 15Changzhou Tumor Hospital, Changzhou, China; 16Fujian Provincial Cancer Hospital, Fuzhou, China; 17Ningbo First Hospital, Ningbo, China; 18Nantong Tumor Hospital, Nantong, China; 19The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China; 20Anhui Provincial Cancer Hospital, Hefei, China; 21Yantai Yuhuangding Hospital, Yantai, China; 22Hubei Cancer Hospital, Wuhan, China; 23Affiliated Cancer Hospital of Shandong First Medical University, Jinan, China; 24Liaoning Cancer Hospital, Shenyang, China; 25Affiliated Hospital of Jiangnan University, Wuxi, China; 26Innovent Biologics, Inc., Suzhou, Ch

Leave a Comment

Your email address will not be published. Required fields are marked *