Caicun Zhou1, Gongyan Chen2, Yunchao Huang3, Jianying Zhou4, LiZhu Lin5, Jifeng Feng6, Zhehai Wang7, Yongqian Shu8, Jianhua Shi9, Yi Hu10, QiMing Wang11, Ying Cheng12, Fengying Wu13, Jianhua Chen14, Xiaoyan Lin15, Yongsheng Wang16, Jianan Huang17, Jiuwei Cui18, Lejie Cao19, Yunpeng Liu20, Yiping Zhang21, Yueyin Pan22, Jun Zhao23, LiPing Wang24, Jianhua Chang25, Qun Chen26, Xiubao Ren27, Wei Zhang28, Yun Fan21, Zhiyong He29, Jian Fang30, Kangsheng Gu31, XiaoRong Dong32, Tao Zhang33, Wei Shi33, Jianjun Zou33. 1. Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China. Electronic address: caicunzhoudr@163.com. 2. Department of Respiratory Medicine, Harbin Medical University Cancer Hospital, Harbin, China. 3. Department of Thoracic Surgery Oncology, Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center, Kunming, China. 4. Respiratory Medicine, The First Affiliated Hospital of Zhejiang University, Hangzhou, China. 5. Oncology Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. 6. Department of Thoracic Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China. 7. Department of Respiratory, Shandong Cancer Hospital & Institute, Jinan, China. 8. Department of Oncology, Jiangsu Province Hospital, Nanjing, China. 9. Department of Medical Oncology, Linyi Cancer Hospital, Linyi, China. 10. Oncology Department, General Hospital of Chinese People's Liberation Army, Beijing, China. 11. Respiratory Medicine, Henan Cancer Hospital, Zhengzhou, China. 12. Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, China. 13. Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China. 14. Department of Medical Oncology-Chest, Hunan Cancer Hospital, Changsha, China. 15. Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, China. 16. Department of Thoracic Medical Oncology, West China Hospital, Sichuan University, Chengdu, China. 17. Department of Respiration, First Affiliated Hospital of Suzhou University, Suzhou, China. 18. Department of Medical Oncology, The First Bethune Hospital of Jilin University, Changchun, China. 19. Pulmonary and Critical Care Medicine, The First Affiliated Hospital University of Science Technology of China, Hefei, China. 20. Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China. 21. Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China. 22. Department of Tumor Chemotherapy, The First Affiliated Hospital University of Science Technology of China, Hefei, China. 23. Department of Thoracic Medical Oncology, Peking University Cancer Hospital & Institute, Beijing, China. 24. Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 25. Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. 26. Department of Oncology, Fuzhou Pulmonary Hospital of Fujian, Fuzhou, China. 27. Department of Biotherapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China. 28. Pneumology Department, The First Affiliated Hospital of Nanchang University, Nanchang, China. 29. Department of Thoracic Oncology, Fujian Cancer Hospital, Fuzhou, China. 30. Department of Thoracic Oncology II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China. 31. Department of Medical Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. 32. Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 33. Clinical Research & Development, Jiangsu Hengrui Medicine, Shanghai, China.
Abstract
BACKGROUND:Immunotherapy combined with chemotherapy has been shown to be efficacious as treatment for advanced non-squamous non-small-cell lung cancer (NSCLC) without targetable genetic aberrations; however, there is scarce evidence of the effectiveness of the combinations in the Asian population. We evaluated camrelizumab plus chemotherapy againstnon-squamous NSCLC in China. METHODS: We did a randomised, open-label, multicentre, phase 3 trial (CameL) in 52 hospitals in China for patients with non-squamous NSCLC without EGFR and ALK alteration. Eligible patients were aged 18-70 years and had no previous systemic chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (version 1.1). Patients were randomly assigned (1:1) to receive 4-6 cycles of carboplatin (area under curve 5 mg/mL per min) plus pemetrexed (500 mg/m2) with or without camrelizumab (200 mg) every 3 weeks, followed by maintenance therapy with camrelizumab plus pemetrexed or pemetrexed alone. Medication was administered intravenously on day 1 of each 3-week treatment cycle. Randomisation was done using a centralised interactive web-response system with the block size randomly generated as four or six and stratified by sex and smoking history. The two primary endpoints were progression-free survival per blinded independent central review, in all patients and in patients who were PD-L1 positive. Primary analysis was done in the full analysis set that included all randomly assigned patients who received at least one dose of the study treatment. Herein, due to the primary endpoint being met at the interim analysis, we reported the findings of prespecified interim analysis, which only included confirmatory statistical testing for progression-free survival in all patients. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT03134872 (follow-up is ongoing). FINDINGS:Between May 12, 2017, and June 6, 2018, of the 419 patients who were randomly assigned, seven did not receive assigned treatment and 412 received either camrelizumab plus chemotherapy (n=205) or chemotherapy alone (n=207). At interim analysis, median follow-up duration was 11·9 months (IQR 9·0-14·9). Progression-free survival in this interim analysis was significantly prolonged with camrelizumab plus chemotherapy than with chemotherapy alone (median 11·3 months [95% CI 9·6-15·4] vs 8·3 months [6·0-9·7]; hazard ratio 0·60 [0·45-0·79]; one-sided p=0·0001). Most common grade 3 or worse treatment-related adverse events were decreased neutrophil count (78 [38%] patients in the camrelizumab plus chemotherapy group vs 63 [30%] patients in the chemotherapy alone group), decreased white blood cell count (40 [20%] vs 30 [14%]), anaemia (38 [19%] vs 23 [11%]), and decreased platelet count (34 [17%] vs 24 [12%]). Serious treatment-related adverse events occurred in 74 (36%) patients in the camrelizumab plus chemotherapy group and 27 (13%) patients in the chemotherapy alone group. INTERPRETATION: The primary endpoint was met at the interim analysis, showing a statistically significant and clinically meaningful improvement in progression-free survival with camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in all patients, supporting camrelizumab plus carboplatin and pemetrexed as a first-line treatment option for Chinese patients with advanced non-squamous NSCLC without EGFR and ALK alterations. The trial is being continued to collect long-term outcomes in all patients and carry out confirmatory statistical testing for progression-free survival in the PD-L1-positive population. FUNDING: Jiangsu Hengrui Medicine.
RCT Entities:
BACKGROUND: Immunotherapy combined with chemotherapy has been shown to be efficacious as treatment for advanced non-squamous non-small-cell lung cancer (NSCLC) without targetable genetic aberrations; however, there is scarce evidence of the effectiveness of the combinations in the Asian population. We evaluated camrelizumab plus chemotherapy against non-squamous NSCLC in China. METHODS: We did a randomised, open-label, multicentre, phase 3 trial (CameL) in 52 hospitals in China for patients with non-squamous NSCLC without EGFR and ALK alteration. Eligible patients were aged 18-70 years and had no previous systemic chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (version 1.1). Patients were randomly assigned (1:1) to receive 4-6 cycles of carboplatin (area under curve 5 mg/mL per min) plus pemetrexed (500 mg/m2) with or without camrelizumab (200 mg) every 3 weeks, followed by maintenance therapy with camrelizumab plus pemetrexed or pemetrexed alone. Medication was administered intravenously on day 1 of each 3-week treatment cycle. Randomisation was done using a centralised interactive web-response system with the block size randomly generated as four or six and stratified by sex and smoking history. The two primary endpoints were progression-free survival per blinded independent central review, in all patients and in patients who were PD-L1 positive. Primary analysis was done in the full analysis set that included all randomly assigned patients who received at least one dose of the study treatment. Herein, due to the primary endpoint being met at the interim analysis, we reported the findings of prespecified interim analysis, which only included confirmatory statistical testing for progression-free survival in all patients. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT03134872 (follow-up is ongoing). FINDINGS: Between May 12, 2017, and June 6, 2018, of the 419 patients who were randomly assigned, seven did not receive assigned treatment and 412 received either camrelizumab plus chemotherapy (n=205) or chemotherapy alone (n=207). At interim analysis, median follow-up duration was 11·9 months (IQR 9·0-14·9). Progression-free survival in this interim analysis was significantly prolonged with camrelizumab plus chemotherapy than with chemotherapy alone (median 11·3 months [95% CI 9·6-15·4] vs 8·3 months [6·0-9·7]; hazard ratio 0·60 [0·45-0·79]; one-sided p=0·0001). Most common grade 3 or worse treatment-related adverse events were decreased neutrophil count (78 [38%] patients in the camrelizumab plus chemotherapy group vs 63 [30%] patients in the chemotherapy alone group), decreased white blood cell count (40 [20%] vs 30 [14%]), anaemia (38 [19%] vs 23 [11%]), and decreased platelet count (34 [17%] vs 24 [12%]). Serious treatment-related adverse events occurred in 74 (36%) patients in the camrelizumab plus chemotherapy group and 27 (13%) patients in the chemotherapy alone group. INTERPRETATION: The primary endpoint was met at the interim analysis, showing a statistically significant and clinically meaningful improvement in progression-free survival with camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in all patients, supporting camrelizumab plus carboplatin and pemetrexed as a first-line treatment option for Chinese patients with advanced non-squamous NSCLC without EGFR and ALK alterations. The trial is being continued to collect long-term outcomes in all patients and carry out confirmatory statistical testing for progression-free survival in the PD-L1-positive population. FUNDING: Jiangsu Hengrui Medicine.
Authors: Brijesh V Patel; Shlomi Haar; Rhodri Handslip; John R Prowle; Zudin Puthucheary; Aldo A Faisal; Chaiyawan Auepanwiriyakul; Teresa Mei-Ling Lee; Sunil Patel; J Alex Harston; Feargus Hosking-Jervis; Donna Kelly; Barnaby Sanderson; Barbara Borgatta; Kate Tatham; Ingeborg Welters; Luigi Camporota; Anthony C Gordon; Matthieu Komorowski; David Antcliffe Journal: Intensive Care Med Date: 2021-05-11 Impact factor: 17.440