{
  "abstract": "Abstract Objective To compare camrelizumab plus capecitabine and oxaliplatin followed by camrelizumab plus apatinib (camre+CAPOX followed by camre+apa), CAPOX alone, and camrelizumab plus CAPOX followed by camrelizumab (camre+CAPOX followed by camre) as initial treatment for gastric or gastro-oesophageal junction adenocarcinoma.Design Randomised, open label, phase 3 study.Setting 75 hospitals in China, 13 March 2019 to 16 August 2021.Participants 885 adults (≥18 years) with previously untreated, human epidermal growth factor receptor 2 (HER2) negative, unresectable, locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma.Interventions Patients were randomised (2:2:1) to receive camre+CAPOX followed by camre+apa, CAPOX only, or camre+CAPOX followed by camre, stratified by Eastern Cooperative Oncology Group performance status, peritoneal metastasis, and programmed death ligand 1 (PD-L1) combined positive score. Assignment to camre+CAPOX followed by camre was introduced midway through enrolment.Main outcome measures The primary endpoint was overall survival for camre+CAPOX followed by camre+apa versus CAPOX alone in the PD-L1 positive population (combined positive score >1) and the overall population who received at least one dose of study drug. Comparisons of camre+CAPOX followed by camre versus CAPOX alone and of camre+CAPOX followed by camre+apa versus camre+CAPOX–camre were descriptive. Safety was assessed in all patients who received at least one dose of study drug.Results 352 patients received camre+CAPOX followed by camre+apa, 349 received CAPOX alone, and 177 received camre+CAPOX followed by camre. At the time of data cut off, 454 of 592 (76.7%) deaths had occurred in the PD-L1 positive population and 709 of 878 (80.8%) in the overall population. Overall survival was longer with camre+CAPOX followed by camre+apa than with CAPOX alone in the PD-L1 positive population (median 15.0 v 12.5 months; hazard ratio 0.80 (95% CI 0.65 to 0.98); one sided P=0.02) and in the overall population (median 13.5 v 12.1 months; hazard ratio 0.80 (0.68 to 0.94); one sided P=0.004). Use of camre+CAPOX followed by camre also showed longer overall survival versus CAPOX in the PD-L1 positive population (median 15.3 v 12.5 months; hazard ratio 0.76 (0.58 to 0.97); one sided nominal P=0.01) and overall population (median 14.2 v 12.1 months; hazard ratio 0.80 (0.65 to 0.98); one sided nominal P=0.02). No overall survival benefit was observed with camre+CAPOX followed by camre+apa versus camre+CAPOX followed by camre. Treatment related adverse events of grade ≥3 occurred in 239 of 352 (67.9%) patients in the camre+CAPOX followed by camre+apa group, 158 of 349 (45.3%) in the CAPOX alone group, and 83 of 177 (46.9%) in the camre+CAPOX followed by camre group.Conclusions Initial treatment with camrelizumab plus CAPOX followed by camrelizumab based maintenance was associated with longer overall survival than CAPOX alone in human epidermal growth factor receptor 2 (HER2) negative, unresectable, locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Exploratory comparisons between the two camrelizumab based regimens showed no additional survival benefit, with higher rates of treatment related adverse events of grade ≥3 and treatment discontinuations when apatinib was added during maintenance.Trial registration ClinicalTrials.gov NCT03813784",
  "authors": [
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, China",
        "Beijing Key Laboratory of Cell and Gene Therapy for Solid Tumour, Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, China"
      ],
      "name": "Zhi Peng"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Harbin Medical University Cancer Hospital, Harbin, China"
      ],
      "name": "Yanqiao Zhang"
    },
    {
      "affiliations": [
        "Department of Abdominal Oncology, Hubei Cancer Hospital, Wuhan, China"
      ],
      "name": "Huiting Xu"
    },
    {
      "affiliations": [
        "Department of Digestive Tumour, Gansu Provincial Cancer Hospital, Lanzhou, China"
      ],
      "name": "Yan Yang"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Shanxi Provincial Cancer Hospital, Taiyuan, China",
        "Shanxi Hospital, Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, China"
      ],
      "name": "Mudan Yang"
    },
    {
      "affiliations": [
        "Department of Oncology, Second Affiliated Hospital of Anhui Medical University, Hefei, China"
      ],
      "name": "Mingjun Zhang"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Jilin Cancer Hospital, Changchun, China"
      ],
      "name": "Ying Cheng"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Henan Cancer Hospital, Zhengzhou, China"
      ],
      "name": "Xiaobing Chen"
    },
    {
      "affiliations": [
        "Division of Life Sciences and Medicine, First Affiliated Hospital of USTC, Hefei, China"
      ],
      "name": "Yueyin Pan"
    },
    {
      "affiliations": [
        "Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"
      ],
      "name": "Feng Wang"
    },
    {
      "affiliations": [
        "Department of Oncology, Affiliated Hospital of Chengde Medical College, Chengde, China"
      ],
      "name": "Qingshan Li"
    },
    {
      "affiliations": [
        "Department of Oncology, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China"
      ],
      "name": "Nong Xu"
    },
    {
      "affiliations": [
        "Department of Oncology, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan, China"
      ],
      "name": "Likun Liu"
    },
    {
      "affiliations": [
        "Department of Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, China"
      ],
      "name": "Kangsheng Gu"
    },
    {
      "affiliations": [
        "Department of Oncology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China"
      ],
      "name": "Juxiang Xiao"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Fourth Hospital of Hebei Medical University, Shijiazhuang, China"
      ],
      "name": "Ruixing Zhang"
    },
    {
      "affiliations": [
        "Department of Surgery (Third Division), Fourth Hospital of Hebei Medical University, Shijiazhuang, China"
      ],
      "name": "Qun Zhao"
    },
    {
      "affiliations": [
        "Department of Gastrointestinal Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"
      ],
      "name": "Jian Chen"
    },
    {
      "affiliations": [
        "Cancer Centre, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China"
      ],
      "name": "Lizhu Lin"
    },
    {
      "affiliations": [
        "Department of Abdominal Oncology, Fujian Provincial Cancer Hospital, Fuzhou, China"
      ],
      "name": "Yigui Chen"
    },
    {
      "affiliations": [
        "Department of Oncology, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China",
        "Guangdong Gastrointestinal Hospital, Guangzhou, China"
      ],
      "name": "Yanhong Deng"
    },
    {
      "affiliations": [
        "Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China"
      ],
      "name": "Shirong Cai"
    },
    {
      "affiliations": [
        "Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals, Shanghai, China"
      ],
      "name": "Bin Bai"
    },
    {
      "affiliations": [
        "Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals, Shanghai, China"
      ],
      "name": "Yiru Wang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, China",
        "Beijing Key Laboratory of Cell and Gene Therapy for Solid Tumour, Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, China"
      ],
      "name": "Lin Shen"
    }
  ],
  "title": "Camrelizumab plus CAPOX with camrelizumab based maintenance versus CAPOX alone as initial treatment for gastric or gastro-oesophageal junction adenocarcinoma: randomised phase 3 trial",
  "uid": "d9c5ef52-422d-54b0-a3d6-a6cf89060eb6"
}