Benmelstobart With or Without Anlotinib After Chemoradiotherapy for Unresectable Non−Small Cell Lung Cancer
Yongling Ji, Qiwen Li, Long Chen, Qingsong Pang, Ou Jiang, Yuanyuan Chen, Jin Wang, Hong Ge, Yufeng Cheng, Rongrong Zhou, Xiangjiao Meng, Xuhong Min, Hui Wang, Haihua Yang, Yue Xie, Anping Zheng, Jie Li, Bing Xia, Desheng Hu, Xi Zhang, Fang Peng, Wenhui Li, Baoqing Chen, Rui Li, Shuohan Zheng, Ling Cai, Shubi Li, Yujin Xu, Wei Feng, Xiaojing Lai, Liming Sheng, Xiaojiang Sun, Zhun Wang, Min Fang, Yang Yang, Yin Yang, Ming ChenImportance
Consolidation immunotherapy improves outcomes after chemoradiotherapy for unresectable stage III non–small cell lung cancer (NSCLC). Disease progression remains common, and more effective consolidation strategies are needed.
Objective
To evaluate the efficacy and safety of benmelstobart with or without anlotinib as consolidation therapy after chemoradiotherapy for unresectable stage III NSCLC.
Design, Setting, and Participants
This multicenter double-blind phase 3 randomized clinical trial took place at 42 centers in China from 2020 to 2023 among patients with unresectable stage III NSCLC without progression after concurrent or sequential chemoradiotherapy. In stage 1, patients were randomized 1:1:1 to 2 active regimens or placebo; in stage 2, additional patients were randomized 1:1 between the active regimens to power their direct comparison. Data cutoffs were November 30, 2023, for stage 1 and July 8, 2024, for the pooled analysis. Data analysis was performed from January 17 to March 23, 2025.
Interventions
Patients were randomized to receive benmelstobart plus anlotinib, benmelstobart plus anlotinib placebo, or their matching placebos.
Main Outcomes and Measures
Primary end point was independent review committee (IRC)−assessed progression-free survival (PFS).
Results
Of 553 participants (median [IQR] age, 62 [56-67] years; 495 male individuals [89.5%]), 390 were randomized in stage 1 and 163 in stage 2. In stage 1, median PFS was 15.1 months (95% CI, 9.4-21.7) with benmelstobart plus anlotinib, 9.7 months (95% CI, 6.0-34.4) with benmelstobart alone, and 4.2 months (95% CI, 3.2-6.8) with placebo. The hazard ratios (HRs) were 0.49 (95% CI, 0.36-0.66; P < .001) for benmelstobart plus anlotinib vs placebo and 0.53 (95% CI, 0.39-0.72; P < .001) for benmelstobart vs placebo. In the pooled stage 1 and 2 analysis, median PFS was 17.4 (95% CI, 12.5-24.8) months with benmelstobart plus anlotinib and 11.2 (95% CI, 7.0-20.7) months with benmelstobart alone (HR, 0.82; 95% CI, 0.63-1.08; P = .12). Grade 3 to 5 treatment-related adverse events occurred in 48.8%, 29.4%, and 19.7% in the benmelstobart plus anlotinib, benmelstobart alone, and placebo groups, respectively; grade 5 events occurred in 7.2%, 1.4%, and 1.5%, respectively.
Conclusions and Relevance
This randomized clinical trial found that benmelstobart with or without anlotinib significantly improved PFS compared with placebo. Adding anlotinib did not significantly improve PFS compared with benmelstobart alone and increased severe and fatal treatment-related adverse events.
Trial Registration
ClinicalTrials.gov Identifier: