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)

作     者：Yuankai Shi Lin Wu Xinmin Yu Puyuan Xing Yan Wang Jianying Zhou Airong Wang Jianhua Shi Yi Hu Ziping Wang Guangyu An Yong Fang Sanyuan Sun Caicun Zhou Changli Wang Feng Ye Xingya Li Junye Wang Mengzhao Wang Yunpeng Liu Yanqiu Zhao Ying Yuan Jifeng Feng Zhendong Chen Jindong Shi Tao Sun Gang Wu Yongqian Shu Qisen Guo Yi Zhang Yong Song Shucai Zhang Yuan Chen Wei Li Hongrui Niu Wenwei Hu Lijun Wang Jianan Huang Yang Zhang Ying Cheng Zhengdong Wu Bo Peng Jiya Sun Christoph Mancao Yanqi Wang Luyao Sun 

作者机构：Department of Medical OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted DrugsBeijingP.R.China Department II of Thoracic MedicineHunan Cancer HospitalChangshaHunanP.R.China Department of Medical OncologyZhejiang Cancer HospitalHangzhouZhejiangP.R.China Department of Respiratory DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP.R.China The Third Department of ChemotherapyWeihai Municipal HospitalWeihaiShandongP.R.China Department of Medical OncologyLinyi Cancer HospitalLinyiShandongP.R.China Oncology DepartmentGeneral Hospital of Chinese People’s Liberation ArmyBeijingP.R.China Department of Chest MedicineBeijing Cancer HospitalBeijingP.R.China Department of OncologyBeijing Chao-Yang HospitalCapital Medical UniversityBeijingP.R.China Department of Medical OncologySir Run Run Shaw HospitalZhejiang UniversityHangzhouZhejiangP.R.China Department of Medical OncologyXuzhou Central HospitalXuzhou Medical UniversityXuzhouJiangsuP.R.China Department of Medical OncologyShanghai Pulmonary HospitalTongji UniversityShanghaiP.R.China Department of Lung CancerTianjin Medical University Cancer Institute and HospitalTianjinP.R.China Department of Medical OncologyCancer HospitalThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityThe Third Clinical Medical CollegeFujian Medical UniversityXiamenFujianP.R.China Department of Medical OncologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanP.R.China Department of OncologyAffiliated Hospital of Jining Medical UniversityJiningShandongP.R.China Department of Respiratory and Critical Care MedicinePeking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingP.R.China Department of Medical OncologyKey Laboratory of Anticancer Drugs and Biotherapy of Liaoning ProvinceThe First Hospital of China Medical UniversityShenyangLiaoningP.R.China Department of Internal MedicineHenan Cancer HospitalAffiliated Cancer Hospital of Zhengzhou UniversityZhengzhouHenanP.R.China Department of Medical OncologyThe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiangP.R.China Department of Medical OncologyJiangsu Cancer HospitalJiangsu Institute of Cancer ResearchThe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjingJiangsuP.R.China Department of OncologyThe Second Hospital of Anhui Medical UniversityHefeiAnhuiP.R.China Department of Respiratory MedicineShanghai Fifth’People’s HospitalFudan UniversityShanghaiP.R.China Department of Medical OncologyCancer Hospital of China Medical UniversityLiaoning Cancer Hospital&InstituteShenyangLiaoningP.R.China Cancer CenterUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Department of OncologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuP.R.China Department of OncologyShandong Cancer Hospital Affiliated to Shandong UniversityShandong Academy of Medical SciencesShandong Cancer Hospital and InstituteJinanShandongP.R.China Department of Thoracic SurgeryXuanwu HospitalCapital Medical UniversityBeijingP.R.China Department of Respiratory and Critical Care MedicineThe General Hospital of the Eastern Theater Command of PLANanjingJiangsuP.R.China Department of OncologyBeijing Chest HospitalCapital Medical UniversityBeijing Tuberculosis and Thoracic Tumor Research InstituteBeijingP.R.China Department of OncologyTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Cancer CenterThe First Hospital of Jilin UniversityChangchunJilinP.R.China Department of OncologyThe First Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenanP.R.China Department of OncologyThe First People’s Hospital of ChangzhouChangzhouJiangsuP.R.China Department of Tumor RadiotherapyThe Second Affiliated Hospital of Xingtai Medical CollegeXingtaiHebeiP.R.China Department of Respiratory MedicineThe First Affiliated Hospital of Soochow UniversitySuzhouJiangsuP.R.China Department of OncologyThe Second Hospital of Dalian Medical UniversityDalianLiaoningP.R.China Department of Thoracic OncologyJilin Cancer HospitalChangchunJilinP.R.China Department of OncologyJiangsu Taizhou People’s HospitalTaizhouJiangsuP.R.China New Drug Biology and Translational MedicineInnovent BiologicsInc.SuzhouJiangsuP.R.China Medical Science and Strategy OncologyInnovent BiologicsInc.SuzhouJiangsuP.R.China 

出 版 物：《Cancer Communications》 (癌症通讯（英文）)

年 卷 期：2022年第42卷第12期

页      面：1314-1330页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：funded by Innovent biologics,Inc. Eli Lilly and Company partly supported by China National Major Project for New Drug Innovation(2017ZX09304015). 

主　　题：Non-small cell lung cancer Carcinoma squamous cell Sintilimab Immunotherapy Survival Randomized controlled trial 

摘      要：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/m^(2) 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 fromthe docetaxel armwere excluded.Themedian 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;P0.001)and showed higher ORR(25.50%vs.2.20%,P0.001)and DCR(65.50%vs.37.80%,P0.001)than the docetaxel arm.The median DoRwas 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≥3were 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;P0.001)and CTCF(HR:3.50;P0.001),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.