Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial.

Autor:	Lu S; Department of Medical Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China., Zhang W; First Affiliated Hospital of Nanchang University, Nanchang, China., Wu L; Department of Thoracic Medical Oncology, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China., Wang W; Second Department of Thoracic Surgery, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China., Zhang P; Shanghai Pulmonary Hospital, Tong Ji University, Shanghai, China., Fang W; Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China., Xing W; Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China., Chen Q; Zhejiang Cancer Hospital, Hangzhou, China., Yang L; Shenzhen People's Hospital, Shenzhen Institute of Respiratory Diseases, Shenzhen, China., Mei J; West China Hospital, Sichuan University, Chengdu, China., Tan L; Zhongshan Hospital, Fudan University, Shanghai, China., Sun X; Cancer Hospital affiliated with Xinjiang Medical University, Urumqi, China., Xu S; Harbin Medical University Cancer Hospital, Harbin, China., Hu X; Tumor Hospital affiliated with Guangxi Medical University, Nanning, China., Yu G; Weifang People's Hospital, Weifang, China., Yu D; Second Affiliated Hospital of Nanchang University, Nanchang, China., Yang N; Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China., Chen Y; Cancer Hospital affiliated with Shantou University Medical College, Shantou, China., Shan J; Daping Hospital, Army Medical University, Chongqing, China., Xing L; Shandong Cancer Hospital and Institute, Jinan, China., Tian H; Qilu Hospital affiliated with Shandong University, Jinan, China., Zhang X; Tianjin Chest Hospital, Tianjin, China., Zhou M; Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China., Fang H; Anhui Chest Hospital, Hefei, China., Wu G; Meizhou People's Hospital (Huangtang Hospital), Meizhou, China., Liu Y; First Hospital of China Medical University, Shenyang., Ye M; Taizhou Hospital of Zhejiang Province, Taizhou, China., Cao L; Anhui Provincial Hospital, Hefei, China., Jiang J; First Affiliated Hospital of Xiamen University, Xiamen, China., Li X; First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Zhu L; Central Hospital affiliated with Shandong First Medical University, Jinan, China., Li D; Peking Union Medical College Hospital, Beijing, China., Kang M; Fujian Medical University Union Hospital, Fuzhou, China., Zhong A; Fuzhou Tuberculosis Control Hospital of Fujian, Fuzhou Pulmonary Hospital of Fujian, Fuzhou, China., Chen K; Beijing Cancer Hospital, Beijing, China., Wu N; Beijing Cancer Hospital, Beijing, China., Sun Q; Henan Provincial Chest Hospital, Zhengzhou, China., Ma H; First Affiliated Hospital of Soochow University, Suzhou, China., Cai K; Nanfang Hospital Southern Medical University, Guangzhou, China., Wang C; Tianjin Cancer Hospital, Tianjin, China., Lin G; Fujian Cancer Hospital, Fuzhou, China., Zhu K; Fujian Cancer Hospital, Fuzhou, China., Zhang Y; Nanjing Chest Hospital Medical School of Southern University, Nanjing, China., Zhang X; Affiliated Hospital of Medical College Qingdao University, Qingdao, China., Hu H; Fudan University Shanghai Cancer Center, Shanghai, China., Zhang W; Tonghua Central Hospital, Tonghua, China., Chen J; Tianjin Medical University General Hospital, Tianjin, China., Yang Z; Affiliated Hospital of Guangdong Medical University, Guangzhou, China., Hang X; Affiliated Hospital of Jiangnan University, Wuxi, China., Hu J; First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Huang Y; Yunnan Cancer Hospital, Kunming, China., Zhang Z; First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China., Zhang L; Jilin Province People's Hospital, Changchun, China., Zhang L; First Affiliated Hospital of Xinjiang Medical University, Urumqi, China., Liu L; West China Hospital, Sichuan University, Chengdu, China., Lin D; Beijing Cancer Hospital, Beijing, China., Zhang J; Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China., Chen G; Zhongshan Hospital, Fudan University, Shanghai, China., Li Y; Fudan University Shanghai Cancer Center, Shanghai, China., Zhu L; Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China., Wang W; Shanghai Junshi Biosciences, Shanghai, China., Yu W; Shanghai Junshi Biosciences, Shanghai, China., Cao D; Shanghai Junshi Biosciences, Shanghai, China., Keegan P; TopAlliance Biosciences, Rockville, Maryland., Yao S; Shanghai Junshi Biosciences, Shanghai, China.; TopAlliance Biosciences, Rockville, Maryland.
Jazyk:	angličtina
Zdroj:	JAMA [JAMA] 2024 Jan 16; Vol. 331 (3), pp. 201-211.
DOI:	10.1001/jama.2023.24735
Abstrakt:	Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.
Databáze:	MEDLINE
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