Huiyan Luo1,2, Jin Lu3, Yuxian Bai4, Teng Mao5, Jun Wang6, Qingxia Fan7, Yiping Zhang8, Kuaile Zhao9, Zhendong Chen10, Shegan Gao11, Jiancheng Li12, Zhichao Fu13, Kangsheng Gu14, Zhihua Liu15, Lin Wu16, Xiaodong Zhang17, Jifeng Feng18, Zuoxing Niu19, Yi Ba20, Helong Zhang21, Ying Liu22, Li Zhang23, Xuhong Min24, Jing Huang25, Ying Cheng26, Dong Wang27, Yu Shen28, Qing Yang28, Jianjun Zou28, Rui-Hua Xu1,2. 1. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. 2. Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China. 3. Sichuan Cancer Hospital, Chengdu, China. 4. Harbin Medical University Cancer Hospital, Harbin, China. 5. Shanghai Chest Hospital, Shanghai, China. 6. The Fourth Hospital of Hebei Medical University, Shijiazhuang, China. 7. The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 8. Zhejiang Cancer Hospital, Hangzhou, China. 9. Fudan University Shanghai Cancer Center, Shanghai, China. 10. The Second Affiliated Hospital of Anhui Medical University, Hefei, China. 11. The First Affiliated Hospital of Henan University of Science & Technology, Luoyang, China. 12. Fujian Provincial Cancer Hospital, Fuzhou, China. 13. 900 Hospital of the Joint Logistics Support Force, Fuzhou, China. 14. The First Affiliated Hospital of Anhui Medical University, Hefei, China. 15. Jiangxi Provincial Cancer Hospital, Nanchang, China. 16. Hunan Cancer Hospital, Changsha, China. 17. Peking University Cancer Hospital and Institute, Beijing, China. 18. Jiangsu Cancer Hospital, Nanjing, China. 19. Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China. 20. Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. 21. The Second Affiliated Hospital of Air Force Medical University, Xi'an, China. 22. Henan Cancer Hospital, Zhengzhou, China. 23. Chongqing Three Gorges Central Hospital, Chongqing, China. 24. Anhui Chest Hospital, Hefei, China. 25. Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China. 26. Jilin Cancer Hospital, Changchun, China. 27. Army Medical Center of PLA, Chongqing, China. 28. Jiangsu Hengrui Pharmaceuticals Co, Ltd, Shanghai, China.
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.
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.
Authors: Leena Gandhi; Delvys Rodríguez-Abreu; Shirish Gadgeel; Emilio Esteban; Enriqueta Felip; Flávia De Angelis; Manuel Domine; Philip Clingan; Maximilian J Hochmair; Steven F Powell; Susanna Y-S Cheng; Helge G Bischoff; Nir Peled; Francesco Grossi; Ross R Jennens; Martin Reck; Rina Hui; Edward B Garon; Michael Boyer; Belén Rubio-Viqueira; Silvia Novello; Takayasu Kurata; Jhanelle E Gray; John Vida; Ziwen Wei; Jing Yang; Harry Raftopoulos; M Catherine Pietanza; Marina C Garassino Journal: N Engl J Med Date: 2018-04-16 Impact factor: 91.245
Authors: Barbara Burtness; Kevin J Harrington; Richard Greil; Denis Soulières; Makoto Tahara; Gilberto de Castro; Amanda Psyrri; Neus Basté; Prakash Neupane; Åse Bratland; Thorsten Fuereder; Brett G M Hughes; Ricard Mesía; Nuttapong Ngamphaiboon; Tamara Rordorf; Wan Zamaniah Wan Ishak; Ruey-Long Hong; René González Mendoza; Ananya Roy; Yayan Zhang; Burak Gumuscu; Jonathan D Cheng; Fan Jin; Danny Rischin Journal: Lancet Date: 2019-11-01 Impact factor: 79.321