Sintilimab versus docetaxel as second-line treatment in advanced or metastatic squamous non-small-cell lung cancer: an open-label, randomized controlled phase 3 trial (ORIENT-3)
Corresponding Author
Yuankai Shi
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, P. R. China
Correspondence
Yuankai Shi, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, P. R. China.
Email: [email protected]
Jifeng Feng, Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, 42 Baiziting, Xuanwu District, Nanjing, Jiangsu 210009, P. R. China.
Email: [email protected]
Search for more papers by this authorLin Wu
Department II of Thoracic Medicine, Hunan Cancer Hospital, Changsha, Hunan, P. R. China
Search for more papers by this authorXinmin Yu
Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, P. R. China
Search for more papers by this authorPuyuan Xing
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, P. R. China
Search for more papers by this authorYan Wang
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, P. R. China
Search for more papers by this authorJianying Zhou
Department of Respiratory Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P. R. China
Search for more papers by this authorAirong Wang
The Third Department of Chemotherapy, Weihai Municipal Hospital, Weihai, Shandong, P. R. China
Search for more papers by this authorJianhua Shi
Department of Medical Oncology, Linyi Cancer Hospital, Linyi, Shandong, P. R. China
Search for more papers by this authorYi Hu
Oncology Department, General Hospital of Chinese People's Liberation Army, Beijing, P. R. China
Search for more papers by this authorZiping Wang
Department of Chest Medicine, Beijing Cancer Hospital, Beijing, P. R. China
Search for more papers by this authorGuangyu An
Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, P. R. China
Search for more papers by this authorYong Fang
Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, P. R. China
Search for more papers by this authorSanyuan Sun
Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou Medical University, Xuzhou, Jiangsu, P. R. China
Search for more papers by this authorCaicun Zhou
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, P. R. China
Search for more papers by this authorChangli Wang
Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P. R. China
Search for more papers by this authorFeng Ye
Department of Medical Oncology, Cancer Hospital, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, The Third Clinical Medical College, Fujian Medical University, Xiamen, Fujian, P. R. China
Search for more papers by this authorXingya Li
Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China
Search for more papers by this authorJunye Wang
Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, Shandong, P. R. China
Search for more papers by this authorMengzhao Wang
Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China
Search for more papers by this authorYunpeng Liu
Department of Medical Oncology, Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, Liaoning, P. R. China
Search for more papers by this authorYanqiu Zhao
Department of Internal Medicine, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China
Search for more papers by this authorYing Yuan
Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, P. R. China
Search for more papers by this authorCorresponding Author
Jifeng Feng
Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, P. R. China
Correspondence
Yuankai Shi, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, P. R. China.
Email: [email protected]
Jifeng Feng, Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, 42 Baiziting, Xuanwu District, Nanjing, Jiangsu 210009, P. R. China.
Email: [email protected]
Search for more papers by this authorZhendong Chen
Department of Oncology, The Second Hospital of Anhui Medical University, Hefei, Anhui, P. R. China
Search for more papers by this authorJindong Shi
Department of Respiratory Medicine, Shanghai Fifth’ People's Hospital, Fudan University, Shanghai, P. R. China
Search for more papers by this authorTao Sun
Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, P. R. China
Search for more papers by this authorGang Wu
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
Search for more papers by this authorYongqian Shu
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P. R. China
Search for more papers by this authorQisen Guo
Department of Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Shandong Cancer Hospital and Institute, Jinan, Shandong, P. R. China
Search for more papers by this authorYi Zhang
Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, P. R. China
Search for more papers by this authorYong Song
Department of Respiratory and Critical Care Medicine, The General Hospital of the Eastern Theater Command of PLA, Nanjing, Jiangsu, P. R. China
Search for more papers by this authorShucai Zhang
Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, P. R. China
Search for more papers by this authorYuan Chen
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
Search for more papers by this authorWei Li
Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, P. R. China
Search for more papers by this authorHongrui Niu
Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, P. R. China
Search for more papers by this authorWenwei Hu
Department of Oncology, The First People's Hospital of Changzhou, Changzhou, Jiangsu, P. R. China
Search for more papers by this authorLijun Wang
Department of Tumor Radiotherapy, The Second Affiliated Hospital of Xingtai Medical College, Xingtai, Hebei, P. R. China
Search for more papers by this authorJianan Huang
Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China
Search for more papers by this authorYang Zhang
Department of Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, P. R. China
Search for more papers by this authorYing Cheng
Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, Jilin, P. R. China
Search for more papers by this authorZhengdong Wu
Department of Oncology, Jiangsu Taizhou People's Hospital, Taizhou, Jiangsu, P. R. China
Search for more papers by this authorBo Peng
New Drug Biology and Translational Medicine, Innovent Biologics, Inc., Suzhou, Jiangsu, P. R. China
Search for more papers by this authorJiya Sun
New Drug Biology and Translational Medicine, Innovent Biologics, Inc., Suzhou, Jiangsu, P. R. China
Search for more papers by this authorChristoph Mancao
New Drug Biology and Translational Medicine, Innovent Biologics, Inc., Suzhou, Jiangsu, P. R. China
Search for more papers by this authorYanqi Wang
Medical Science and Strategy Oncology, Innovent Biologics, Inc., Suzhou, Jiangsu, P. R. China
Search for more papers by this authorLuyao Sun
Medical Science and Strategy Oncology, Innovent Biologics, Inc., Suzhou, Jiangsu, P. R. China
Search for more papers by this authorCorresponding Author
Yuankai Shi
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, P. R. China
Correspondence
Yuankai Shi, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, P. R. China.
Email: [email protected]
Jifeng Feng, Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, 42 Baiziting, Xuanwu District, Nanjing, Jiangsu 210009, P. R. China.
Email: [email protected]
Search for more papers by this authorLin Wu
Department II of Thoracic Medicine, Hunan Cancer Hospital, Changsha, Hunan, P. R. China
Search for more papers by this authorXinmin Yu
Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, P. R. China
Search for more papers by this authorPuyuan Xing
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, P. R. China
Search for more papers by this authorYan Wang
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, P. R. China
Search for more papers by this authorJianying Zhou
Department of Respiratory Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P. R. China
Search for more papers by this authorAirong Wang
The Third Department of Chemotherapy, Weihai Municipal Hospital, Weihai, Shandong, P. R. China
Search for more papers by this authorJianhua Shi
Department of Medical Oncology, Linyi Cancer Hospital, Linyi, Shandong, P. R. China
Search for more papers by this authorYi Hu
Oncology Department, General Hospital of Chinese People's Liberation Army, Beijing, P. R. China
Search for more papers by this authorZiping Wang
Department of Chest Medicine, Beijing Cancer Hospital, Beijing, P. R. China
Search for more papers by this authorGuangyu An
Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, P. R. China
Search for more papers by this authorYong Fang
Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, P. R. China
Search for more papers by this authorSanyuan Sun
Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou Medical University, Xuzhou, Jiangsu, P. R. China
Search for more papers by this authorCaicun Zhou
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, P. R. China
Search for more papers by this authorChangli Wang
Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P. R. China
Search for more papers by this authorFeng Ye
Department of Medical Oncology, Cancer Hospital, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, The Third Clinical Medical College, Fujian Medical University, Xiamen, Fujian, P. R. China
Search for more papers by this authorXingya Li
Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China
Search for more papers by this authorJunye Wang
Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, Shandong, P. R. China
Search for more papers by this authorMengzhao Wang
Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China
Search for more papers by this authorYunpeng Liu
Department of Medical Oncology, Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, Liaoning, P. R. China
Search for more papers by this authorYanqiu Zhao
Department of Internal Medicine, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China
Search for more papers by this authorYing Yuan
Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, P. R. China
Search for more papers by this authorCorresponding Author
Jifeng Feng
Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, P. R. China
Correspondence
Yuankai Shi, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, P. R. China.
Email: [email protected]
Jifeng Feng, Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, 42 Baiziting, Xuanwu District, Nanjing, Jiangsu 210009, P. R. China.
Email: [email protected]
Search for more papers by this authorZhendong Chen
Department of Oncology, The Second Hospital of Anhui Medical University, Hefei, Anhui, P. R. China
Search for more papers by this authorJindong Shi
Department of Respiratory Medicine, Shanghai Fifth’ People's Hospital, Fudan University, Shanghai, P. R. China
Search for more papers by this authorTao Sun
Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, P. R. China
Search for more papers by this authorGang Wu
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
Search for more papers by this authorYongqian Shu
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P. R. China
Search for more papers by this authorQisen Guo
Department of Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Shandong Cancer Hospital and Institute, Jinan, Shandong, P. R. China
Search for more papers by this authorYi Zhang
Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, P. R. China
Search for more papers by this authorYong Song
Department of Respiratory and Critical Care Medicine, The General Hospital of the Eastern Theater Command of PLA, Nanjing, Jiangsu, P. R. China
Search for more papers by this authorShucai Zhang
Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, P. R. China
Search for more papers by this authorYuan Chen
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
Search for more papers by this authorWei Li
Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, P. R. China
Search for more papers by this authorHongrui Niu
Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, P. R. China
Search for more papers by this authorWenwei Hu
Department of Oncology, The First People's Hospital of Changzhou, Changzhou, Jiangsu, P. R. China
Search for more papers by this authorLijun Wang
Department of Tumor Radiotherapy, The Second Affiliated Hospital of Xingtai Medical College, Xingtai, Hebei, P. R. China
Search for more papers by this authorJianan Huang
Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China
Search for more papers by this authorYang Zhang
Department of Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, P. R. China
Search for more papers by this authorYing Cheng
Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, Jilin, P. R. China
Search for more papers by this authorZhengdong Wu
Department of Oncology, Jiangsu Taizhou People's Hospital, Taizhou, Jiangsu, P. R. China
Search for more papers by this authorBo Peng
New Drug Biology and Translational Medicine, Innovent Biologics, Inc., Suzhou, Jiangsu, P. R. China
Search for more papers by this authorJiya Sun
New Drug Biology and Translational Medicine, Innovent Biologics, Inc., Suzhou, Jiangsu, P. R. China
Search for more papers by this authorChristoph Mancao
New Drug Biology and Translational Medicine, Innovent Biologics, Inc., Suzhou, Jiangsu, P. R. China
Search for more papers by this authorYanqi Wang
Medical Science and Strategy Oncology, Innovent Biologics, Inc., Suzhou, Jiangsu, P. R. China
Search for more papers by this authorLuyao Sun
Medical Science and Strategy Oncology, Innovent Biologics, Inc., Suzhou, Jiangsu, P. R. China
Search for more papers by this authorTrial registration: NSCLC, NCT03150875. Registered May 12, 2017, https://clinicaltrials.gov/ct2/show/NCT03150875
Abstract
Background
Treatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer (sqNSCLC) after failure of first-line chemotherapy are limited. This study (ORIENT-3) aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second-line treatment in patients with locally advanced or metastatic sqNSCLC.
Methods
ORIENT-3 was an open-label, multicenter, randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first-line platinum-based chemotherapy. Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m2 of docetaxel intravenously every 3 weeks, stratified by the Eastern Cooperative Oncology Group performance status. The primary endpoint was overall survival (OS) in the full analysis set (FAS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety.
Results
Between August 25, 2017, and November 7, 2018, 290 patients were randomized. For FAS, 10 patients from the docetaxel arm were excluded. The median OS was 11.79 (n = 145; 95% confidence interval [CI], 10.28-15.57) months with sintilimab versus 8.25 (n = 135; 95% CI, 6.47-9.82) months with docetaxel (hazard ratio [HR]: 0.74; 95% CI, 0.56-0.96; P = 0.025). Sintilimab treatment significantly prolonged PFS (median 4.30 vs. 2.79 months; HR: 0.52; 95% CI, 0.39-0.68; P < 0.001) and showed higher ORR (25.50% vs. 2.20%, P < 0.001) and DCR (65.50% vs. 37.80%, P < 0.001) than the docetaxel arm. The median DoR was 12.45 (95% CI, 4.86-25.33) months in the sintilimab arm and 4.14 (95% CI, 1.41-7.23) months in the docetaxel arm (P = 0.045). Treatment-related adverse events of grade ≥ 3 were reported in 26 (18.1%) patients in the sintilimab arm and 47 (36.2%) patients in the docetaxel arm. Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors, including OVOL2 (HR: 0.35; P < 0.001) and CTCF (HR: 3.50; P < 0.001)，for sintilimab treatment.
Conclusions
Compared with docetaxel, sintilimab significantly improved the OS, PFS, and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC.
CONFLICT OF INTEREST
Disclosure: Bo Peng, Jiya Sun, Christoph Mancao, Yanqi Wang and Luyao Sun are full-time employees of Innovent Biologics,Inc. The other authors declare that they have no competing interests.
Open Research
DATA AVAILABILITY STATEMENT
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| cac212385-sup-0001-SuppMat.docx1.2 MB | Supporting information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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