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. (19th April 2022)

• Record Type: Journal Article
• Authors: Lu, Zhihao; Wang, Junye; Shu, Yongqian; Liu, Lianke; Kong, Li; Yang, Lei; Wang, Buhai; Sun, Guogui; Ji, Yinghua; Cao, Guochun; Liu, Hu; Cui, Tongjian; Li, Na; Qiu, Wensheng; Li, Gaofeng; Hou, Xinfang; Luo, Hui; Xue, Liying; Zhang, Yanqiao; Yue, Wenbin; Liu, Zheng; Wang, Xiuwen; Gao, Shegan; Pan, Yueyin; Galais, Marie-Pierre; Zaanan, Aziz; Ma, Zhuo; Li, Haoyu; Wang, Yan; Shen, Lin
• Other Names: author non-byline.; Pan Zhanyu author non-byline.; Zhang Shuqun author non-byline.; Lin Gen author non-byline.; Xie Yanru author non-byline.; Li Tao author non-byline.; Ren Tiejun author non-byline.; Li Weidong author non-byline.; Gu Kangsheng author non-byline.; Wang Shoufeng author non-byline.; He Wei author non-byline.; Xia Bing author non-byline.; Fan Yun author non-byline.; Liang Jun author non-byline.; Zhao Kuaile author non-byline.; Pan Hongming author non-byline.; Xu Nong author non-byline.; Cheng Ying author non-byline.; Gao Quanli author non-byline.; Sun Ping author non-byline.; Zang Aimin author non-byline.; Zheng Anping author non-byline.; Luo Zhiguo author non-byline.; Liu Tianshu author non-byline.; Ding Shubo author non-byline.; Xu Tianwen author non-byline.; Li Wei author non-byline.; Liu Fang author non-byline.; Cang Shundong author non-byline.; Wang Junsheng author non-byline.; Lin Xiaoyan author non-byline.; Jiang Da author non-byline.; Mao Rui author non-byline.; Ma Dong author non-byline.; Liu Yunpeng author non-byline.; Tao Min author non-byline.; Tang Yong author non-byline.; Chen Xi author non-byline.; Chen Ping author non-byline.; Feng Guosheng author non-byline.; Yang Zhenzhou author non-byline.; Zhang Guifang author non-byline.; Zhang Xuebang author non-byline.; Huang Yong author non-byline.; Lee Fa-Chyi author non-byline.; Dean Andrew author non-byline.; El Hajbi Farid author non-byline.; Ghiringhelli François author non-byline.; Borg Christophe author non-byline.; Tougeron David author non-byline.; Dahan Laetitia author non-byline.; Pernot Simon author non-byline.; Rivera Fernando author non-byline.; Pazo Cid Roberto Antonio author non-byline.; Vazquez Rivera Maria Francisca author non-byline.;
• Is Part Of: BMJ. Volume 377(2022)
• Publication Date: 2022-04-19
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Medicine; Periodicals; 610
• DOI: 10.1136/bmj-2021-068714
• Languages: English
• ISSNs: 0007-1447

Abstract

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 analysis, sintilimab with chemotherapy showed better overall survival compared with placebo and chemotherapy in all patients (median 16.7 v 12.5 months, hazard ratio 0.63, 95% confidence interval 0.51 to 0.78, P<0.001) and in patients with combined positive scores of ≥10 (17.2 v 13.6 months, 0.64, 0.48 to 0.85, P=0.002). Sintilimab and chemotherapy significantly improved progression free survival compared with placebo and chemotherapy in all patients (7.2 v 5.7 months, 0.56, 0.46 to 0.68, P<0.001) and in patients with combined positive scores of ≥10 (8.3 v 6.4 months, 0.58, 0.45 to 0.75, P<0.001). Adverse events related to treatment occurred in 321 of 327 patients (98%) in the sintilimab-chemotherapy group versus 326 of 332 (98%) patients in the placebo-chemotherapy group. Rates of adverse events related to treatment, grade ≥3, were 60% (196/327) and 55% (181/332) in the sintilimab-chemotherapy and placebo-chemotherapy groups, respectively. Conclusions: Compared with placebo, sintilimab in combination with cisplatin plus paclitaxel showed significant benefits in overall survival and progression free survival as first line treatment in patients with advanced or metastatic oesophageal squamous cell carcinoma. Similar benefits of sintilimab with cisplatin plus 5-fluorouracil seem promising. Trial registration: ClinicalTrials.gov NCT03748134 .