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Original Investigation
September 14, 2021

Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial

Author Affiliations
  • 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
  • 2Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China
  • 3Sichuan Cancer Hospital, Chengdu, China
  • 4Harbin Medical University Cancer Hospital, Harbin, China
  • 5Shanghai Chest Hospital, Shanghai, China
  • 6The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
  • 7The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
  • 8Zhejiang Cancer Hospital, Hangzhou, China
  • 9Fudan University Shanghai Cancer Center, Shanghai, China
  • 10The Second Affiliated Hospital of Anhui Medical University, Hefei, China
  • 11The First Affiliated Hospital of Henan University of Science & Technology, Luoyang, China
  • 12Fujian Provincial Cancer Hospital, Fuzhou, China
  • 13900 Hospital of the Joint Logistics Support Force, Fuzhou, China
  • 14The First Affiliated Hospital of Anhui Medical University, Hefei, China
  • 15Jiangxi Provincial Cancer Hospital, Nanchang, China
  • 16Hunan Cancer Hospital, Changsha, China
  • 17Peking University Cancer Hospital and Institute, Beijing, China
  • 18Jiangsu Cancer Hospital, Nanjing, China
  • 19Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China
  • 20Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
  • 21The Second Affiliated Hospital of Air Force Medical University, Xi'an, China
  • 22Henan Cancer Hospital, Zhengzhou, China
  • 23Chongqing Three Gorges Central Hospital, Chongqing, China
  • 24Anhui Chest Hospital, Hefei, China
  • 25Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China
  • 26Jilin Cancer Hospital, Changchun, China
  • 27Army Medical Center of PLA, Chongqing, China
  • 28Jiangsu Hengrui Pharmaceuticals Co, Ltd, Shanghai, China
JAMA. 2021;326(10):916-925. doi:10.1001/jama.2021.12836
Visual Abstract. Effect of Camrelizumab Plus Chemotherapy as a First-line Treatment for Esophageal Squamous Cell Carcinoma
Effect of Camrelizumab Plus Chemotherapy as a First-line Treatment for Esophageal Squamous Cell Carcinoma
Key Points

Question  Does the addition of camrelizumab to chemotherapy improve outcomes when used as first-line treatment for patients with advanced or metastatic esophageal squamous cell carcinoma?

Findings  In this randomized clinical trial that included 596 patients with advanced or metastatic esophageal squamous cell carcinoma, camrelizumab combined with chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival (15.3 vs 12.0 months, respectively; hazard ratio for death, 0.70) and progression-free survival (6.9 vs 5.6 months, respectively; hazard ratio for disease progression or death, 0.56).

Meaning  Among patients with advanced or metastatic esophageal squamous cell carcinoma, an initial treatment strategy of camrelizumab combined with chemotherapy, compared with placebo and chemotherapy, resulted in improved overall survival and progression-free survival.

Abstract

Importance  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.

Objective  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.

Design, Setting, and Participants  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.

Interventions  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/m2) and cisplatin (75 mg/m2). All treatments were given intravenously every 3 weeks.

Main Outcomes and Measures  Coprimary end points were overall survival (significance threshold, 1-sided P < .02) and progression-free survival (significance threshold, 1-sided P < .005).

Results  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 P = .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 P < .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.

Conclusions and Relevance  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.

Trial Registration  ClinicalTrials.gov Identifier: NCT03691090

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