Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma
Authors: Huiyan Luo, Jin Lu, Yuxian Bai, Teng Mao, Jun Wang, Qingxia Fan, Yiping Zhang, Kuaile Zhao, Zhendong Chen, Shegan Gao, Jiancheng Li, Zhichao Fu, Kangsheng Gu, Zhihua Liu, Lin Wu, Xiaodong Zhang, Jifeng Feng, Zuoxing Niu, Yi Ba, Helong Zhang, Ying Liu, Li Zhang, Xuhong Min, Jing Huang, Ying Cheng, Dong Wang, Yu Shen, Qing Yang, Jianjun Zou, Rui-Hua Xu, Xianglin Yuan, Dong Ma, Li Liu, Feng Ye, Tianshu Liu, Xiuwen Wang, Likun Liu, Bing Xia, Fengming Ran, Sanyuan Sun, Zhanhui Miao, Jun Bie, Yong Gao, Junyan Yu, Li Chen, Yifu He, Wei Ren, Suxia Luo, Guangqiang Zhao, Youen Lin, Long Chen, Zhiyuan Guo, Chunhong Hu, Ying Wang, Nong Xu, Baofu Chen, Xianbao Zhan, Yuping Chen, Hongda Lu, Shukui Qin, Guolei Wang, Liming Chen, Li Bai, Jingdong Zhang
Journal: JAMA (2021)

<h3>Importance</h3> Standard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti–programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma. <h3>Objective</h3> To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma. <h3>Design, Setting, and Participants</h3> This randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020). A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized. <h3>Interventions</h3> Patients were randomized 1:1 to receive either camrelizumab 200 mg (n = 298) or placebo (n = 298), combined with up to 6 cycles of paclitaxel (175 mg/m<sup>2</sup>) and cisplatin (75 mg/m<sup>2</sup>). All treatments were given intravenously every 3 weeks. <h3>Main Outcomes and Measures</h3> Coprimary end points were overall survival (significance threshold, 1-sided<i>P</i> &lt; .02) and progression-free survival (significance threshold, 1-sided<i>P</i> &lt; .005). <h3>Results</h3> Of the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumab-chemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided<i>P</i> = .001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided<i>P</i> &lt; .001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively. <h3>Conclusions and Relevance</h3> Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03691090