机构：[1]Department of Oncology, Jilin Cancer Hospital, Changchun, China. [2]Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China. [3]Second Department of Thoracic Medical Oncology, Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China. [4]Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. [5]Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, China. [6]Department of Oncology, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou, China. [7]Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China. [8]Department of Respiratory, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China. [9]Department of Respiration, First People's Hospital of Changzhou, Third Affiliated Hospital of Soochow University, Changzhou, China. [10]Department of Respiratory Medicine, Taizhou Hospital, Taizhou, China. 台州恩泽医疗中心台州医院[11]Department of Respiratory Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China. 河南省肿瘤医院[12]First Department of Internal Medicine, Harbin Medical University Affiliated Cancer Hospital, Harbin, China. [13]Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Sciences, Xiangyang, China. [14]Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China. [15]Department of Respiratory Medicine, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha, China. [16]The Second Department of Medical Oncology, Yunnan Cancer Hospital, Kunming, China. [17]Department of Medical Oncology, Chongqing University Three Gorges Hospital, Chongqing, China. [18]Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China. 四川大学华西医院[19]Department of Oncology, Second Affiliated Hospital of Anhui Medical University Hefei, Hefei, China. [20]Department of Tumor Chemotherapy, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Hefei, China. [21]Department of Respiratory Disease, Zhejiang Provincial People's Hospital, Hangzhou, China. [22]Ward I Chest Medicine, Hubei Cancer Hospital, Wuhan, China. [23]Department of Respiratory Medicine, Shandong Cancer Hospital and Institute, Jinan, China. [24]Second Department of Internal Medicine, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China. [25]Second Department of Thoracic Oncology, Beijing Cancer Hospital, Beijing, China. [26]Department of Respiratory Medicine, Tangdu Hospital, The Second Affiliated Hospital of the Chinese People's Liberation Army Air Force Medical University, Xi'an, China. [27]Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China. [28]First Department of Oncology, Shenyang the Tenth People's Hospital, Shenyang, China. [29]Department of Respiratory Medicine, Anhui Provincial Cancer Hospital, Hefei, China. [30]Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China. [31]Department of Respiratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China. [32]Department of Medical Oncology, Anhui Chest Hospital, Hefei, China. [33]Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. [34]Department of Medical Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. [35]Department of Respiratory Medicine, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, China. 河北医科大学第四医院[36]Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. [37]Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. [38]Department of Respiratory, Hainan General Hospital, Haikou, China. [39]Department of Respiratory Medicine, Shanghai Chest Hospital, Jiao Tong University, Shanghai, China. [40]Department of Medical Oncology, Ruian People's Hospital, Ruian, China. [41]Department of Oncology, Binzhou Medical University Hospital, Binzhou, China. [42]Department of Pneumology, Fujian Provincial Cancer Hospital, Fuzhou, China. [43]Pulmonary Medicine, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, China. [44]Department of Oncology, Inner Mongolia Autonomous Region People's Hospital, Hohhot, China. [45]Department of Oncology, Shaoxing People's Hospital, Shaoxing, China. [46]Department of Oncology, The 960th Hospital of People's Liberation Army, Jinan, China. 中国人民解放军联勤保障部队第九六〇医院[47]Department of Oncology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China. [48]Department of Oncology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. [49]Department of Respiratory, First Affiliated Hospital of Xian Jiaotong University, Xi'an, China. [50]Shanghai Junshi Biosciences Co Ltd, Shanghai, China. [51]TopAlliance Biosciences Inc, Rockville, Maryland.
Patients with extensive-stage small cell lung cancer (ES-SCLC) have poor prognoses and unmet medical needs.To evaluate the efficacy and safety of toripalimab plus etoposide and platinum-based chemotherapy (EP) vs placebo plus EP as a first-line treatment for patients with ES-SCLC.This multicenter, double-blind, placebo-controlled phase 3 randomized clinical trial (EXTENTORCH study) enrolled patients from September 26, 2019, to May 20, 2021, and was conducted at 49 sites in China. Eligible patients had histologically or cytologically confirmed ES-SCLC without previous systemic antitumor therapy for ES-SCLC. Data were analyzed between May 6, 2023, and June 1, 2024.Patients were randomized (1:1) to receive toripalimab, 240 mg, or placebo plus EP every 3 weeks for up to 4 to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxic effects, or up to 2 years of treatment.The primary end points were investigator-assessed progression-free survival (PFS) and overall survival (OS). Whole-exome sequencing results identified correlative biomarkers for clinical efficacy.Among 595 screened patients, 442 eligible patients were randomized (median [range] age, 63 [30-77] years; 366 [82.8%] male); 223 patients were randomized to toripalimab plus EP, and 219 to placebo plus EP. By April 20, 2023, the median (range) survival follow-up was 13.7 (0.0-42.7) months. Compared with placebo, toripalimab improved investigator-assessed PFS (hazard ratio [HR], 0.67 [95% CI, 0.54-0.82]; P < .001), and significantly reduced the risk of death (HR, 0.80 [95% CI, 0.65-0.98]; P = .03). The median OS was 14.6 (95% CI, 12.9-16.6) months in the toripalimab group vs 13.3 (95% CI, 11.8-14.4) months in the placebo group. Whole-exome sequencing results from 300 patients identified low intratumor heterogeneity, HLA-A11+ HLA-B62- haplotype, wild-type KMT2D and COL4A4, or sequence variations in CTNNA2 or SCN4A correlated with favorable PFS and OS in the toripalimab group. No new safety signals were observed. Grade 3 or higher treatment-emergent adverse event incidence was similar between the toripalimab and placebo safety set groups (199 of 222 patients [89.6%] vs 193 of 216 patients [89.4%], respectively).In this phase 3 randomized clinical trial, adding toripalimab to first-line chemotherapy demonstrated significant improvements in PFS and OS for patients with ES-SCLC. The treatment exhibited an acceptable safety profile, supporting this combination regimen as a new treatment option for patients with ES-SCLC.ClinicalTrials.gov Identifier: NCT04012606.
基金：
This work was supported by
Shanghai Junshi Biosciences Co Ltd.
第一作者机构：[1]Department of Oncology, Jilin Cancer Hospital, Changchun, China.
通讯作者：
推荐引用方式(GB/T 7714)：
Cheng Ying,Zhang Wei,Wu Lin,et al.Toripalimab Plus Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Lung Cancer: The Phase 3 EXTENTORCH Randomized Clinical Trial[J].JAMA Oncology.2025,11(1):16-25.doi:10.1001/jamaoncol.2024.5019.
APA：
Cheng Ying,Zhang Wei,Wu Lin,Zhou Caicun,Wang Donglin...&Yu Jianjun.(2025).Toripalimab Plus Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Lung Cancer: The Phase 3 EXTENTORCH Randomized Clinical Trial.JAMA Oncology,11,(1)
MLA：
Cheng Ying,et al."Toripalimab Plus Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Lung Cancer: The Phase 3 EXTENTORCH Randomized Clinical Trial".JAMA Oncology 11..1(2025):16-25
医学