Yunpeng Yang1, Zhehai Wang2, Jian Fang3, Qitao Yu4, Baohui Han5, Shundong Cang6, Gongyan Chen7, Xiaodong Mei8, Zhixiong Yang9, Rui Ma10, Minghong Bi11, Xiubao Ren12, Jianying Zhou13, Baolan Li14, Yong Song15, Jifeng Feng16, Juan Li17, Zhiyong He18, Rui Zhou19, Weimin Li20, You Lu21, Yingyi Wang22, Lijun Wang23, Nong Yang24, Yan Zhang25, Zhuang Yu26, Yanqiu Zhao27, Conghua Xie28, Ying Cheng29, Hui Zhou30, Shuyan Wang30, Donglei Zhu30, Wen Zhang31, Li Zhang32. 1. Medical Oncology Department, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China. 2. Medical Oncology Department, Shandong Cancer Hospital, Jinan, Shandong, People's Republic of China. 3. Department of Thoracic Oncology II, Peking University Cancer Hospital, Beijing, People's Republic of China. 4. Department of Respiratory Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning City, Guangxi, People's Republic of China. 5. Department of Respiration, Shanghai Chest Hospital, Shanghai, People's Republic of China. 6. Department of Oncology, The Henan Province Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China. 7. Department of Respiration, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, People's Republic of China. 8. Department of Respiration, Anhui Provincial Hospital, Hefei, Anhui, People's Republic of China. 9. Department of Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People's Republic of China. 10. Medical Oncology Department of Thoracic Cancer, Liaoning Cancer Hospital, Shenyang, Liaoning, People's Republic of China. 11. Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People's Republic of China. 12. Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China. 13. Department of Respiratory Diseases, The First Affiliated Hospital College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China. 14. Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing, People's Republic of China. 15. Department of Respiratory and Critical Care Medicine, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, Jiangsu, People's Republic of China. 16. Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu, People's Republic of China. 17. Department of Medical Oncology, Sichuan Cancer Hospital, Chengdu, Sichuan, People's Republic of China. 18. Department of Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian, People's Republic of China. 19. Department of Respiration, Xiangya Second Hospital, Changsha, Hunan, People's Republic of China. 20. Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. 21. Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. 22. Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. 23. Department of Tumor Radiotherapy, The Second Affiliated Hospital of Xingtai Medical College, Xingtai, Hebei, People's Republic of China. 24. Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, Hunan, People's Republic of China. 25. Department of Oncology IV, First Hospital of Shijiazhuang, Shijiazhuang, Hebei, People's Republic of China. 26. Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People's Republic of China. 27. Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China. 28. Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China. 29. Department of Medical Oncology, Jilin Cancer Hospital, Changchun, Jilin, People's Republic of China. 30. Medical Science and Strategy Oncology, Innovent Biologics, Inc., Shanghai, People's Republic of China. 31. Department of Biostatistics and Information, Innovent Biologics, Inc., Shanghai, People's Republic of China. 32. Medical Oncology Department, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China. Electronic address: zhangli@sysucc.org.cn.
Abstract
INTRODUCTION: Sintilimab, an anti-programmed death 1 antibody, plus pemetrexed and platinum had revealed promising efficacy for nonsquamous NSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to compare the efficacy and safety of sintilimab with placebo, both in combination with such chemotherapy (ClinicalTrials.gov: NCT03607539). METHODS: A total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC without sensitizing EGFR or anaplastic lymphoma kinase genomic aberration were randomized (2:1 ratio) to receive either sintilimab 200 mg or placebo plus pemetrexed and platinum once every 3 weeks for four cycles, followed by sintilimab or placebo plus pemetrexed therapy. Crossover or treatment beyond disease progression was allowed. The primary end point was progression-free survival (PFS) as judged by an independent radiographic review committee. RESULTS: As of November 15, 2019, the median follow-up was 8.9 months. The median PFS was significantly longer in the sintilimab-combination group than that in the placebo-combination group (8.9 versus 5.0 mo; hazard ratio, 0.482, 95% confidence interval [CI]: 0.362-0.643; p < 0.00001). The confirmed objective response rate was 51.9% (95% CI: 45.7%-58.0%) in the sintilimab-combination group and 29.8% (95% CI: 22.1%-38.4%) in placebo-combination group. The incidence of grade 3 or higher adverse events was 61.7% in sintilimab-combination group and 58.8% in placebo-combination group. CONCLUSIONS: In Chinese patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC, the addition of sintilimab to chemotherapy with pemetrexed and platinum resulted in considerably longer PFS than with chemotherapy alone with manageable safety profiles.
INTRODUCTION: Sintilimab, an anti-programmed death 1 antibody, plus pemetrexed and platinum had revealed promising efficacy for nonsquamous NSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to compare the efficacy and safety of sintilimab with placebo, both in combination with such chemotherapy (ClinicalTrials.gov: NCT03607539). METHODS: A total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC without sensitizing EGFR or anaplastic lymphoma kinase genomic aberration were randomized (2:1 ratio) to receive either sintilimab 200 mg or placebo plus pemetrexed and platinum once every 3 weeks for four cycles, followed by sintilimab or placebo plus pemetrexed therapy. Crossover or treatment beyond disease progression was allowed. The primary end point was progression-free survival (PFS) as judged by an independent radiographic review committee. RESULTS: As of November 15, 2019, the median follow-up was 8.9 months. The median PFS was significantly longer in the sintilimab-combination group than that in the placebo-combination group (8.9 versus 5.0 mo; hazard ratio, 0.482, 95% confidence interval [CI]: 0.362-0.643; p < 0.00001). The confirmed objective response rate was 51.9% (95% CI: 45.7%-58.0%) in the sintilimab-combination group and 29.8% (95% CI: 22.1%-38.4%) in placebo-combination group. The incidence of grade 3 or higher adverse events was 61.7% in sintilimab-combination group and 58.8% in placebo-combination group. CONCLUSIONS: In Chinese patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC, the addition of sintilimab to chemotherapy with pemetrexed and platinum resulted in considerably longer PFS than with chemotherapy alone with manageable safety profiles.