Jing Huang1, Jianming Xu2, Yun Chen3, Wu Zhuang4, Yiping Zhang5, Zhendong Chen6, Jia Chen7, Helong Zhang8, Zuoxing Niu9, Qingxia Fan10, Lizhu Lin11, Kangsheng Gu12, Ying Liu13, Yi Ba14, Zhanhui Miao15, Xiaodong Jiang16, Ming Zeng17, Jianhua Chen18, Zhichao Fu19, Lu Gan20, Jun Wang21, Xianbao Zhan22, Tianshu Liu23, Zhiping Li24, Lin Shen25, Yongqian Shu26, Tao Zhang27, Qing Yang27, Jianjun Zou27. 1. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 2. Department of Gastrointestinal Oncology, Cancer Center, Fifth Medical Center General Hospital of PLA, Beijing, China. Electronic address: jmxu2003@yahoo.com. 3. Department of Radiation Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China. 4. Department of Thoracic Medical Oncology, Fujian Province Cancer Hospital, Fuzhou, China. 5. Department of Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou, China. 6. Oncology Department, The Second Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China. 7. Department of Oncology, Jiangsu Cancer Hospital, Nanjing, China. 8. Oncology Department, Tangdu Hospital of the Fourth Military Medical University, Xi'an, China. 9. Internal Medicine Ward 4, Shandong Cancer Hospital, Jinan, China. 10. Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 11. Oncology Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. 12. Medical Oncology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China. 13. Medical Oncology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China. 14. Medical Oncology, Tianjin Cancer Hospital, Tianjin, China. 15. Oncology Department, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China. 16. Oncology Department, The First People's Hospital of Lianyungang, Lianyungang, China. 17. Oncology Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China. 18. Department of Medical Oncology, Cancer Hospital of Central South University, Changsha, China. 19. Department of Radiotherapy, 900 Hospital of the Joint Logistics Team, Fuzhou, China. 20. The Oncology Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. 21. Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China. 22. Department of Medical Oncology, Changhai Hospital, Second Military Medical University, Shanghai, China. 23. Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China. 24. Integrated Chinese and Western Medical Oncology, Jiangxi Cancer Hospital, Nanchang, China. 25. Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China. 26. Medical Oncology, Jiangsu Province Hospital, Nanjing, China. 27. Jiangsu Hengrui Medicine, Shanghai, China.
Abstract
BACKGROUND:Patients with advanced or metastatic oesophageal squamous cell carcinoma have poor prognosis and few treatment options after first-line therapy. We aimed to assess efficacy and safety of the anti-PD-1 antibody camrelizumab versus investigator's choice of chemotherapy in previously treated patients. METHODS: ESCORT is a randomised, open-label, phase 3 study of patients aged 18 to 75 years with a histological or cytological diagnosis of advanced or metastatic oesophageal squamous cell carcinoma done at 43 hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had progressed on, or were intolerant to, first-line standard therapy. Patients were randomly assigned (1:1) to camrelizumab (200 mg every 2 weeks) or chemotherapy with docetaxel (75 mg/m2 every 3 weeks) or irinotecan (180 mg/m2 every 2 weeks), all given intravenously. Central randomisation was done using the Randomization and Trial Supply Management system with block size randomly generated as four or six and stratified by disease and ECOG performance status. The primary endpoint was overall survival, assessed in randomised patients who had received at least one dose of treatment. Safety was assessed in all treated patients. The trial is registered with ClinicalTrials.gov, NCT03099382, and is closed to new participants. FINDINGS:From May 10, 2017, to July 24, 2018, 457 (75%) of 607 screened patients were randomly assigned to treatment, of whom 228 received camrelizumab treatment and 220 received chemotherapy. As of data cutoff on May 6, 2019, with a median follow-up time of 8·3 months (IQR 4·1-12·8) in the camrelizumab group and 6·2 months (3·6-10·1) in the chemotherapy group, median overall survival was 8·3 months (95% CI 6·8-9·7) in the camrelizumab group and 6·2 months (5·7-6·9) in the chemotherapy group (hazard ratio 0·71 [95% CI 0·57-0·87]; two-sided p=0·0010). The most common treatment-related adverse events of grade 3 or worse were anaemia (camrelizumab vs chemotherapy: six [3%] vs 11 [5%]), abnormal hepatic function (four [2%] vs one [<1%]), and diarrhoea (three [1%] vs nine [4%]). Serious treatment-related adverse events occurred in 37 (16%) of 228 patients in the camrelizumab group, and in 32 (15%) of 220 patients in the chemotherapy group. Ten treatment-related deaths occurred, seven (3%) in the camrelizumab group (three deaths from unknown causes, one enterocolitis, one hepatic function abnormal, one pneumonitis, and one myocarditis) and three (1%) in the chemotherapy group (two deaths from unknown causes, and one gastrointestinal haemorrhage). INTERPRETATION: Second-line camrelizumab significantly improved overall survival in patients with advanced or metastatic oesophageal squamous cell carcinoma compared with chemotherapy, with a manageable safety profile. It might represent a potential option of standard second-line treatment for patients with oesophageal squamous cell carcinoma in China. FUNDING: Jiangsu Hengrui Medicine.
RCT Entities:
BACKGROUND:Patients with advanced or metastatic oesophageal squamous cell carcinoma have poor prognosis and few treatment options after first-line therapy. We aimed to assess efficacy and safety of the anti-PD-1 antibody camrelizumab versus investigator's choice of chemotherapy in previously treated patients. METHODS: ESCORT is a randomised, open-label, phase 3 study of patients aged 18 to 75 years with a histological or cytological diagnosis of advanced or metastatic oesophageal squamous cell carcinoma done at 43 hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had progressed on, or were intolerant to, first-line standard therapy. Patients were randomly assigned (1:1) to camrelizumab (200 mg every 2 weeks) or chemotherapy with docetaxel (75 mg/m2 every 3 weeks) or irinotecan (180 mg/m2 every 2 weeks), all given intravenously. Central randomisation was done using the Randomization and Trial Supply Management system with block size randomly generated as four or six and stratified by disease and ECOG performance status. The primary endpoint was overall survival, assessed in randomised patients who had received at least one dose of treatment. Safety was assessed in all treated patients. The trial is registered with ClinicalTrials.gov, NCT03099382, and is closed to new participants. FINDINGS: From May 10, 2017, to July 24, 2018, 457 (75%) of 607 screened patients were randomly assigned to treatment, of whom 228 received camrelizumab treatment and 220 received chemotherapy. As of data cutoff on May 6, 2019, with a median follow-up time of 8·3 months (IQR 4·1-12·8) in the camrelizumab group and 6·2 months (3·6-10·1) in the chemotherapy group, median overall survival was 8·3 months (95% CI 6·8-9·7) in the camrelizumab group and 6·2 months (5·7-6·9) in the chemotherapy group (hazard ratio 0·71 [95% CI 0·57-0·87]; two-sided p=0·0010). The most common treatment-related adverse events of grade 3 or worse were anaemia (camrelizumab vs chemotherapy: six [3%] vs 11 [5%]), abnormal hepatic function (four [2%] vs one [<1%]), and diarrhoea (three [1%] vs nine [4%]). Serious treatment-related adverse events occurred in 37 (16%) of 228 patients in the camrelizumab group, and in 32 (15%) of 220 patients in the chemotherapy group. Ten treatment-related deaths occurred, seven (3%) in the camrelizumab group (three deaths from unknown causes, one enterocolitis, one hepatic function abnormal, one pneumonitis, and one myocarditis) and three (1%) in the chemotherapy group (two deaths from unknown causes, and one gastrointestinal haemorrhage). INTERPRETATION: Second-line camrelizumab significantly improved overall survival in patients with advanced or metastatic oesophageal squamous cell carcinoma compared with chemotherapy, with a manageable safety profile. It might represent a potential option of standard second-line treatment for patients with oesophageal squamous cell carcinoma in China. FUNDING: Jiangsu Hengrui Medicine.
Authors: Linlin Xiao; Yvonne M Mowery; Brian G Czito; Yajing Wu; Guangbin Gao; Chang Zhai; Jianing Wang; Jun Wang Journal: Front Oncol Date: 2021-04-29 Impact factor: 6.244
Authors: Laercio Lopes da Silva; Pedro Nazareth Aguiar; Robin Park; Eduardo Edelman Saul; Benjamin Haaland; Gilberto de Lima Lopes Journal: Cancers (Basel) Date: 2021-05-26 Impact factor: 6.639