| Title | Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): interim and final analyses of a double-blind, randomised, phase 3 clinical trial |
| Authors | Zhou, Caicun Wang, Ziping Sun, Yuping Cao, Lejie Ma, Zhiyong Wu, Rong Yu, Yan Yao, Wenxiu Chang, Jianhua Chen, Jianhua Zhuang, Wu Cui, Jiuwei Chen, Xueqin Lu, You Shen, Hong Wang, Jingru Li, Peiqi Qin, Mengmeng Lu, Dongmei Yang, Jason |
| Affiliation | Tongji Univ, Shanghai Pulm Hosp, Dept Oncol, Sch Med, Shanghai 200433, Peoples R China Peking Univ, Dept Thorac Oncol, Key Lab Carcinogenesis & Translat Res, Minist Educ,Canc Hosp & Inst, Beijing, Peoples R China Jinan Cent Hosp, Dept Oncol, Jinan, Peoples R China Shandong Canc Hosp & Inst, Phase I Clin Res Ctr, Jinan, Peoples R China Univ Sci & Technol China, Affiliated Hosp 1, Anhui Prov Hosp, Dept Resp Med,Div Life Sci & Med, Hefei, Peoples R China Zhengzhou Univ, Henan Canc Hosp, Dept Resp Med, Affiliated Canc Hosp, Zhengzhou, Peoples R China China Med Univ, Huaxiang Branch Hosp, Shengjing Hosp, Dept Oncol, Shenyang, Peoples R China Harbin Med Univ, Dept Resp Med, Canc Hosp, Harbin, Peoples R China Sichuan Canc Hosp & Inst, Thorac Oncol, Chengdu, Peoples R China Fudan Univ, Dept Oncol, Shanghai Canc Ctr, Shanghai, Peoples R China Chinese Acad Med Sci, Dept Oncol, Shenzhen Ctr, Canc Hosp, Shenzhen, Peoples R China Hunan Canc Hosp, Dept Thorac Oncol, Changsha, Peoples R China Fujian Prov Canc Hosp, Dept Thorac Oncol, Fuzhou, Peoples R China First Hosp Jilin Univ, Pharmacol Base, Changchun, Peoples R China Zhejiang Univ, Sch Med, Affiliated Hangzhou Peoples Hosp 1, Dept Thorac Oncol,Canc Ctr, Hangzhou, Peoples R China Sichuan Univ, West China Hosp, Dept Thorac Oncol, Chengdu, Peoples R China Zhejiang Univ, Dept Oncol, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China CStone Pharmaceut, Clin Dev, Suzhou, Peoples R China |
| Keywords | NONSQUAMOUS NSCLC PLUS CHEMOTHERAPY ATEZOLIZUMAB CARBOPLATIN |
| Issue Date | Feb-2022 |
| Publisher | LANCET ONCOLOGY |
| Abstract | Background PD-1 inhibitor plus chemotherapy had been shown to be an effective first-line treatment for patients with metastatic non-small-cell lung cancer (NSCLC). However, there was no robust evidence showing a PD-L1 inhibitor combined with chemotherapy benefited patients with squamous and non-squamous NSCLC. GEMSTONE-302 aimed to evaluate the efficacy and safety of a PD-L1 inhibitor, sugemalimab, plus chemotherapy for patients with metastatic squamous or non-squamous NSCLC. Methods This randomised, double-blind, phase 3 trial was done in 35 hospitals and academic research centres in China. Eligible patients were aged 18-75 years, had histologically or cytologically confirmed stage IV squamous or non-squamous NSCLC without known EGFR sensitising mutations, ALK, ROS1, or RET fusions, no previous systemic treatment for metastatic disease, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned (2:1) to receive sugemalimab (1200 mg, intravenously, every 3 weeks) plus platinum-based chemotherapy (carboplatin [area under the curve (AUC) S mg/mL per min, intravenously] and paclitaxel [175 mg/m(2), intravenously] for squamous NSCLC, or carboplatin [AUC S mg/mL per min, intravenously] and pemetrexed [500 mg/m(2), intravenously] for non-squamous NSCLC; sugemalimab group) or placebo plus the same platinum-based chemotherapy regimens for squamous or non-squamous NSCLC as in the sugemalimab group; placebo group) for up to four cycles, followed by maintenance therapy with sugemalimab or placebo for squamous NSCLC, and intravenous sugemalimab 500 mg/m(2) or matching placebo plus pemetrexed for non-squamous NSCLC. Randomisation was done by an interactive voice-web-response system via permuted blocks (block size was a mixture of three and six with a random order within each stratum) and stratified by ECOG performance status, PD-L1 expression, and tumour pathology. The investigators, patients, and the sponsor were masked to treatment assignment. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Safety was analysed in all patients who received at least one treatment dose. Results reported are from a prespecified interim analysis (ie, when the study met the primary endpoint) and an updated analysis (prespecified final analysis for progression-free survival) with a longer follow-up. This study is registered with ClinicalTrials.gov (NCT03789604), is closed to new participants, and follow-up is ongoing. Findings Between Dec 13, 2018, and May 15, 2020, 846 patients were assessed for eligibility; 367 were ineligible, and the remaining 479 patients were randomly assigned to the sugemalimab group (n=320) or placebo group (n=159). At the preplanned interim analysis (data cutoff June 8, 2020; median follow-up 8.6 months [IQR 6.1-11.4]), GEMSTONE-302 met its primary endpoint, with significantly longer progression-free survival in the sugemalimab group compared with the placebo group (median 7.8 months [95% CI 6.9-9.0] vs 4.9 months [4.7-5.0]; stratified hazard ratio [Hit] 0.50 [95% CI 0.39-0.64], p<0.0001]). At the final analysis (March 15, 2021) with a median follow-up of 17.8 months (IQR 15.1-20.9), the improvement in progression-free survival was maintained (median 9.0 months [95% CI 7.4-10.8] vs 4.9 months [4.8-5.1]; stratified HR 0.48 [95% CI 0.39-0.60], p<0.0001). The most common grade 3 or 4 any treatment-related adverse events were neutrophil count decreased (104 p3%1 of 320 with sugemalimab vs 52 [33%] of 159 with placebo), white blood cell count decreased (45 [14%] vs 27 117%1), anaemia (43 113%1 vs 18 [11%]), platelet count decreased (33 [10%] vs 15 [9%]), and neutropenia (12 [4%] vs seven [4%]). Any treatment-related serious adverse events occurred in 73 (23%) patients in the sugemalimab group and 31 (20%) patients in the placebo group. Any treatment-related deaths were reported in ten (3%) patients in the sugemalimab group (pneumonia with respiratory failure in one patient; myelosuppression with septic shock in one patient; pneumonia in two patients; respiratory failure, abdominal pain, cardiac failure, and immune-mediated pneumonitis in one patient each; the other two deaths had an unspecified cause) and in two (1%) patients in the placebo group (pneumonia and multiple organ dysfunction syndrome). Interpretation Sugernalimab plus chemotherapy showed a statistically significant and clinically meaningful progression-free survival improvement compared with placebo plus chemotherapy, in patients with previously untreated squamous and non-squamous metastatic NSCLC, regardless of PD-Li expression, and could be a new first-line treatment option for both squamous and non-squamous metastatic NSCLC. Copyright (C) 2022 Elsevier Ltd. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/637716 |
| ISSN | 1470-2045 |
| DOI | 10.1016/S1470-2045(21)00650-1 |
| Indexed | SCI(E) |
| Appears in Collections: | 北京肿瘤医院 |
