Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial

doi:10.1016/S1470-2045(21)00630-6

	Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial
	Zhou, Qing 28; Chen, Ming 26,27; Jiang, Ou 25; Pan, Yi 28; Hu, Desheng 2; Lin, Qin 1; Wu, Gang 24; Cui, Jiuwei 23; Chang, Jianhua 21,22; Cheng, Yufeng 20
刊名	LANCET ONCOLOGY
	2022-02-01
卷号	23
ISSN号	1470-2045
DOI	10.1016/S1470-2045(21)00630-6
通讯作者	Wu, Yi-Long(syylwu@live.cn)
英文摘要	Background A substantial proportion of patients with unresectable stage III non-small-cell lung cancer (NSCLC) cannot either tolerate or access concurrent chemoradiotherapy, so sequential chemoradiotherapy is commonly used. We assessed the efficacy and safety of sugemalimab, an anti-PD-L1 antibody, in patients with stage III NSCLC whose disease had not progressed after concurrent or sequential chemoradiotherapy. Methods GEMSTONE-301 is a randomised, double-blind, placebo-controlled, phase 3 trial in patients with locally advanced, unresectable, stage III NSCLC, done at 50 hospitals or academic research centres in China. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 who had not progressed after concurrent or sequential chemoradiotherapy. We randomly assigned patients (2:1, using an interactive voice-web response system) to receive sugemalimab 1200 mg or matching placebo, intravenously every 3 weeks for up to 24 months. Stratification factors were ECOG performance status, previous chemoradiotherapy, and total radiotherapy dose. The investigators, trial coordination staff, patients, and study sponsor were masked to treatment allocation. The primary endpoint was progression-free survival as assessed by blinded independent central review (BICR) in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of assigned study treatment. The study has completed enrolment and the results of a preplanned analysis of the primary endpoint are reported here. The trial is registered with ClinicalTrials.gov, NCT03728556. Findings Between Aug 30, 2018 and Dec 30, 2020, we screened 564 patients of whom 381 were eligible. Study treatment was received by all patients randomly assigned to sugemalimab (n=255) and to placebo (n=126). At data cutoff (March 8, 2021), median follow-up was 14.3 months (IQR 6.4-19-4) for patients in the sugemalimab group and 13.7 months (7.1-18-4) for patients in the placebo group. Progression-free survival assessed by BICR was significantly longer with sugemalimab than with placebo (median 9.0 months [95% CI 8.1-14.1] vs 5.8 months [9s% CI 4.2-6.6]; stratified hazard ratio 0.64 [95% CI 0-48-0.85], p=0-0026). Grade 3 or 4 treatment-related adverse events occurred in 22 (9%) of 255 patients in the sugemalimab group versus seven (6%) of 126 patients in the placebo group, the most common being pneumonitis or immune-mediated pneumonitis (seven 13%1 of 255 patients in the sugemalimab group vs one (<1%1 of 126 in the placebo group). Treatment-related serious adverse events occurred in 38 (15%) patients in the sugemalimab group and 12 (10%) in the placebo group. Treatment-related deaths were reported in four (2%) of 255 patients (pneumonia in two patients, pneumonia with immune-mediated pneumonitis in one patient, and acute hepatic failure in one patient) in the sugemalimab group and none in the placebo group. Interpretation Sugemalimab after definitive concurrent or sequential chemoradiotherapy could be an effective consolidation therapy for patients with stage III NSCLC whose disease has not progressed after sequential or concurrent chemoradiotherapy. Longer follow-up is needed to confirm this conclusion. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
资助项目	CStone Pharmaceuticals ; National Key Research and Development Program of China
WOS关键词	8TH EDITION ; NSCLC ; CS1001 ; CHEMOTHERAPY ; DURVALUMAB ; MUTATIONS ; PLATINUM ; ANTIBODY
WOS研究方向	Oncology
语种	英语
出版者	ELSEVIER SCIENCE INC
WOS记录号	WOS:000751827100025
资助机构	CStone Pharmaceuticals ; National Key Research and Development Program of China
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/127476]
专题	中国科学院合肥物质科学研究院
通讯作者	Wu, Yi-Long
作者单位	1.Xiamen Univ, Affiliated Hosp 1, Xiamen, Peoples R China 2.Hubei Canc Hosp, Wuhan, Peoples R China 3.CStone Pharmaceut Suzhou, Shanghai, Peoples R China 4.Jiangxi Canc Hosp, Nanchang, Jiangxi, Peoples R China 5.Linyi Canc Hosp, Linyi, Shandong, Peoples R China 6.China Three Gorges Univ, Yichang Cent Peoples Hosp, Coll Clin Med Sci 1, Yichang, Peoples R China 7.China Med Univ, Shengjing Hosp, Shenyang, Peoples R China 8.Army Med Ctr PLA, Chongqing, Peoples R China 9.China Med Univ, Hosp 1, Shenyang, Peoples R China 10.Army Med Univ, Xinqiao Hosp, Chongqing, Peoples R China
推荐引用方式 GB/T 7714	Zhou, Qing,Chen, Ming,Jiang, Ou,et al. Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial[J]. LANCET ONCOLOGY,2022,23.
APA	Zhou, Qing.,Chen, Ming.,Jiang, Ou.,Pan, Yi.,Hu, Desheng.,...&Wu, Yi-Long.(2022).Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial.LANCET ONCOLOGY,23.
MLA	Zhou, Qing,et al."Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial".LANCET ONCOLOGY 23(2022).