Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial

作者：Zhihao Lü, Junye Wang, Yongqian Shu, Lianke Liu, Li Ren Kong, Lei Yang, Buhai Wang, Guogui Sun, Yinghua Ji, Guochun Cao, Hu Liu, Tongjian Cui, Na Li, Wensheng Qiu, Gaofeng Li, Xinfang Hou, Hui Luo, Liying Xue, Yanqiao Zhang, Wenbin Yue, Zheng Liu, Xiuwen Wang, Shegan Gao, Yueyin Pan, Marie‐Pierre Galais, Aziz Zaanan, Zhuo Ma, Haoyu Li, Yan Wang, Lin Shen · 发表于：BMJ · 年份：2022 · DOI：10.1136/bmj-2021-068714 · 被引用次数：493 · 研究领域：Esophageal Cancer Research and Treatment、Cancer Immunotherapy and Biomarkers、Head and Neck Cancer Studies

Abstract Objective To evaluate sintilimab versus placebo in combination with chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil) as first line treatment of unresectable locally advanced, recurrent, or metastatic oesophageal squamous cell carcinoma. Design Multicentre, randomised, double blind, phase 3 trial. Setting 66 sites in China and 13 sites outside of China between 14 December 2018 and 9 April 2021. Participants 659 adults (aged ≥18 years) with advanced or metastatic oesophageal squamous cell carcinoma who had not received systemic treatment. Intervention Participants were randomised 1:1 to receive sintilimab or placebo (3 mg/kg in patients weighing <60 kg or 200 mg in patients weighing ≥60 kg) in combination with cisplatin 75 mg/m 2 plus paclitaxel 175 mg/m 2 every three weeks. The trial was amended to allow investigators to choose the chemotherapy regimen: cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil (800 mg/m 2 continuous infusion on days 1-5). Main outcome measures Overall survival in all patients and in patients with combined positive scores of ≥10 for expression of programmed cell death ligand 1. Results 659 patients were randomly assigned to sintilimab (n=327) or placebo (n=332) with chemotherapy. 616 of 659 patients (93%) received sintilimab or placebo in combination with cisplatin plus paclitaxel and 43 of 659 patients (7%) received sintilimab or placebo in combination with cisplatin plus 5-fluorouracil. At the interim ana...