Yunpeng Yang1, Jiya Sun2, Zhehai Wang3, Jian Fang4, Qitao Yu5, Baohui Han6, Shundong Cang7, Gongyan Chen8, Xiaodong Mei9, Zhixiong Yang10, Rui Ma11, Minghong Bi12, Xiubao Ren13, Jianying Zhou14, Baolan Li15, Yong Song16, Jifeng Feng17, Juan Li18, Zhiyong He19, Rui Zhou20, Weimin Li21, You Lu22, Hui Zhou23, Shuyan Wang23, Luyao Sun23, Oscar Puig24, Christoph Mancao2, Bo Peng2, Wenfeng Fang1, Wei Xu2, Li Zhang25. 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, People's Republic of China. 2. New Drug Biology and Translational Medicine, Innovent Biologics, Inc., Suzhou, People's Republic of China. 3. Medical Oncology Department, Shandong Cancer Hospital, Jinan, People's Republic of China. 4. Department of Thoracic Oncology II, Peking University Cancer Hospital, Beijing, People's Republic of China. 5. Department of Respiratory Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning City, People's Republic of China. 6. Department of Respiration, Shanghai Chest Hospital, Shanghai, People's Republic of China. 7. Department of Oncology, The Henan Province Hospital of Zhengzhou University, Zhengzhou, People's Republic of China. 8. Department of Respiration, Harbin Medical University Cancer Hospital, Harbin, People's Republic of China. 9. Department of Respiration, Anhui Provincial Hospital, Hefei, People's Republic of China. 10. Department of Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China. 11. Medical Oncology Department of Thoracic Cancer, Liaoning Cancer Hospital, Shenyang, People's Republic of China. 12. Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China. 13. Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China. 14. Department of Respiratory Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China. 15. Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing, People's Republic of China. 16. Department of Respiratory and Critical Care Medicine, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, People's Republic of China. 17. Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing, People's Republic of China. 18. Department of Medical Oncology, Sichuan Cancer Hospital, Chengdu, People's Republic of China. 19. Department of Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou, People's Republic of China. 20. Department of Respiration, Xiangya Second Hospital, Changsha, People's Republic of China. 21. Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China. 22. Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, People's Republic of China. 23. Medical Science and Strategy Oncology, Innovent Biologics, Inc., Suzhou, People's Republic of China. 24. Translational Medicine, Oncology Business Unit, Eli Lilly and Company, New York, New York. 25. Medical Oncology Department, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China. Electronic address: zhangli@sysucc.org.cn.
Abstract
INTRODUCTION: Sintilimab plus chemotherapy significantly prolonged progression-free survival (PFS) compared with chemotherapy alone in nonsquamous NSCLC in the ORIENT-11 study. Updated overall survival (OS) and PFS data and corresponding biomarker analyses are reported here. METHODS: In this study, a total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC were assigned to sintilimab plus chemotherapy combination treatment (combo) group or placebo plus chemotherapy treatment group. The patients were stratified by programmed death-ligand 1 (PD-L1) expression levels. Immune signature profiles from tumor RNA sequencing and PD-L1 immunohistochemistry were correlated with clinical outcome to identify predictive biomarkers. RESULTS: As of January 2021, with median follow-up of 22.9 months, median OS was significantly improved in the combo group compared with the placebo plus chemotherapy treatment group (not reached versus 16.8 mo; hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.45-0.79, p = 0.0003). High or medium immune cell infiltration was strongly associated with improved PFS in the combo group, in contrast to absent or low immune cell infiltration, which suggests that chemotherapy could not prime "immune deserts" to obtain benefit from programmed cell death protein-1 inhibition. In particular, high major histocompatibility complex (MHC) class II presentation pathway expression was significantly correlated with prolonged PFS (HR = 0.32, 95% CI: 0.19-0.54, p < 0.0001) and OS (HR = 0.36, 95% CI: 0.20-0.64, p = 0.0005) in the combo group. Importantly, patients with low or absent PD-L1 but high MHC class II expression could still benefit from the combo treatment. In contrast, MHC class I antigen presentation pathway was less relevant in this combination setting. CONCLUSIONS: The addition of sintilimab to chemotherapy resulted to significantly longer OS in nonsquamous NSCLC. Expression of MHC class II antigen presentation pathway could identify patients benefiting most from this combination.
INTRODUCTION: Sintilimab plus chemotherapy significantly prolonged progression-free survival (PFS) compared with chemotherapy alone in nonsquamous NSCLC in the ORIENT-11 study. Updated overall survival (OS) and PFS data and corresponding biomarker analyses are reported here. METHODS: In this study, a total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC were assigned to sintilimab plus chemotherapy combination treatment (combo) group or placebo plus chemotherapy treatment group. The patients were stratified by programmed death-ligand 1 (PD-L1) expression levels. Immune signature profiles from tumor RNA sequencing and PD-L1 immunohistochemistry were correlated with clinical outcome to identify predictive biomarkers. RESULTS: As of January 2021, with median follow-up of 22.9 months, median OS was significantly improved in the combo group compared with the placebo plus chemotherapy treatment group (not reached versus 16.8 mo; hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.45-0.79, p = 0.0003). High or medium immune cell infiltration was strongly associated with improved PFS in the combo group, in contrast to absent or low immune cell infiltration, which suggests that chemotherapy could not prime "immune deserts" to obtain benefit from programmed cell death protein-1 inhibition. In particular, high major histocompatibility complex (MHC) class II presentation pathway expression was significantly correlated with prolonged PFS (HR = 0.32, 95% CI: 0.19-0.54, p < 0.0001) and OS (HR = 0.36, 95% CI: 0.20-0.64, p = 0.0005) in the combo group. Importantly, patients with low or absent PD-L1 but high MHC class II expression could still benefit from the combo treatment. In contrast, MHC class I antigen presentation pathway was less relevant in this combination setting. CONCLUSIONS: The addition of sintilimab to chemotherapy resulted to significantly longer OS in nonsquamous NSCLC. Expression of MHC class II antigen presentation pathway could identify patients benefiting most from this combination.