Toripalimab Plus Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Lung Cancer
Year: 2024
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Importance: Patients with extensive-stage small cell lung cancer (ES-SCLC) have poor prognoses and unmet medical needs. Objective: 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. Design, Setting, and Participants: 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. Interventions: 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. Main Outcomes and Measures: 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. Results: 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). Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT04012606.
Source: JAMA Oncology
Authors: Ying Cheng, Wei Zhang, Lin Wu, Caicun Zhou, Donglin Wang, Bing Xia, Minghong Bi, Xiuhua Fu, Chong Li, Dongqing Lv, Yanqiu Zhao, Gongyan Chen, Tienan Yi, Jianan Huang, Min Li, Runxiang Yang, Xiaoping Huang, Ye Wang, Mingjun Zhang, Yueyin Pan, Yilan Sun, Sheng Hu, Xiqin Zhang, Min Zhou, Jian Fang, Faguang Jin, Yunpeng Liu, Yinyin Li, Zhihong Zhang, Jie Hu, Laiyu Liu, Rui Wang, Yan Li, Kangsheng Gu, Cuimin Ding, Qingxia Fan, Guojun Zhang, Yongxing Chen, Liyan Jiang, Wei-E. Zheng, Shaoshui Chen, Cheng Huang, Zhigang Han, Hong Yang, Jianfang Wang, Baocheng Wang, Huita Wu, Yongxing Bao, Manxiang Li, Xianming Luo, Shanshan Gu, Wenbo Yu, Kai Xu, Simo Zhang, Jianjun Yu
Institutions: Jilin Province Tumor Hospital, First Affiliated Hospital of Nanchang University, Central South University, Hunan Cancer Hospital, Tongji University, Shanghai Pulmonary Hospital, Chongqing University, Chongqing Cancer Hospital, Hangzhou Cancer Hospital, Zhejiang University, First Affiliated Hospital of Bengbu Medical College, Inner Mongolia Medical University, Soochow University, The First People's Hospital of Changzhou, Zhengzhou University, Henan Cancer Hospital, Harbin Medical University, Hubei University of Arts and Science, Xiangyang Central Hospital, First Affiliated Hospital of Soochow University, First Affiliated Hospital of Xi'an Jiaotong University, Xiangya Hospital Central South University, Sichuan University, West China Hospital of Sichuan University, Second Affiliated Hospital of Anhui Medical University, University of Science and Technology of China, Anhui Provincial Hospital, Zhejiang Provincial People's Hospital, Hubei Cancer Hospital, Shandong Tumor Hospital, Guangzhou Medical University Cancer Hospital, Peking University Cancer Hospital, Tang Du Hospital, Chinese People's Liberation Army, People's Liberation Army Air Force, Air Force Medical University, First Hospital of China Medical University, Shandong Provincial QianFoShan Hospital, Shandong First Medical University, Fudan University, Zhongshan Hospital, Nanfang Hospital, Southern Medical University, First Affiliated Hospital of Anhui Medical University, Hebei Medical University, Fourth Hospital of Hebei Medical University, First Affiliated Hospital of Zhengzhou University, Hainan General Hospital, Shanghai Jiao Tong University, Shanghai Chest Hospital, Ruian People's Hospital, Binzhou Medical University, Fujian Provincial Cancer Hospital, Xinjiang Medical University, Tumor Hospital of Xinjiang Medical University, Inner Mongolia People's Hospital, Shaoxing People's Hospital, Xiamen University, Zhongshan Hospital of Xiamen University, First Affiliated Hospital of Xinjiang Medical University, Junshi Biosciences (China), TopAlliance Biosciences (United States)
Language: English
Topic: Lung Cancer Research Studies
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4404348564