Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial

作者：Miao‐Zhen Qiu, Do‐Youn Oh, Ken Kato, Tobias Arkenau, Josep Tabernero, Marcia Cruz Correa, Anastasia Zimina, Yuxian Bai, Jianhua Shi, Keun-Wook Lee, Jufeng Wang, Elena Poddubskaya, Hongming Pan, Sun Young Rha, Ruixing Zhang, Hidekazu Hirano, David R. Spigel, Kensei Yamaguchi, Yee Chao, Lucjan Wyrwicz, Umut Dişel, Roberto Pazo-Cid, Lorenzo Fornaro, Ludovic Evesque, Hongwei Wang, Yaling Xu, Jiang Li, Tao Sheng, Silu Yang, Liyun Li, Markus Moehler, Rui‐Hua Xu · 发表于：BMJ · 年份：2024 · DOI：10.1136/bmj-2023-078876 · 被引用次数：277 · 研究领域：Gastric Cancer Management and Outcomes、Esophageal Cancer Research and Treatment、Cancer Immunotherapy and Biomarkers

Abstract Objective To evaluate the efficacy and safety of tislelizumab added to chemotherapy as first line (primary) treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma compared with placebo plus chemotherapy. Design Randomised, double blind, placebo controlled, phase 3 study. Setting 146 medical centres across Asia, Europe, and North America, between 13 December 2018 and 28 February 2023. Participants 1657 patients aged ≥18 years with human epidermal growth factor receptor 2 negative locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma, regardless of programmed death-ligand 1 (PD-L1) expression status, who had not received systemic anticancer therapy for advanced disease. Interventions Patients were randomly (1:1) assigned to receive either tislelizumab 200 mg or placebo intravenously every three weeks in combination with chemotherapy (investigator’s choice of oxaliplatin and capecitabine, or cisplatin and 5-fluorouracil) and stratified by region, PD-L1 expression, presence or absence of peritoneal metastases, and investigator’s choice of chemotherapy. Treatment continued until disease progression or unacceptable toxicity. Main outcome measures The primary endpoint was overall survival, both in patients with a PD-L1 tumour area positivity (TAP) score of ≥5% and in all randomised patients. Safety was assessed in all those who received at least one dose of study treatment. Results Of 1657 patients screened b...