Anlotinib combined with benmelstobart as a chemo-free first-line treatment in advanced esophageal squamous cell carcinoma: an exploratory multicenter, single-arm phase II clinical trial

作者：Xiangrui Meng, Xiuli Yang, Yonggui Hong, Wenkang Wang, Zhiye Zhang, Jin Xia, Yunfang Chen, Yue Zhou, Taiying Lu, Min Seob Song, Zhengzheng Shan, Tao Wu, Weilong Wu, Ling Shen, Lulu Guan, Mingying Ma, Lisen Wang, Xi Luo, Dao Xin, Yihui Ma, Guozhong Jiang, Yu Qi, Bing‐Hua Jiang, Daoyu Zhang, Biao Hu, Xiaoying Wu, Zuofu Peng, Feng Wang · 发表于：Molecular Cancer · 年份：2025 · DOI：10.1186/s12943-025-02376-w · 被引用次数：10 · 研究领域：Esophageal Cancer Research and Treatment、Lung Cancer Research Studies、Cancer Immunotherapy and Biomarkers

BACKGROUND: No combined antiangiogenic and PD-1/PD-L1 blockade therapy has been investigated as a chemo-free first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). This study evaluates the efficacy and safety of anlotinib combined with benmelstobart as a chemo-free treatment in previously untreated advanced ESCC, and identifies potential predictive biomarkers using next-generation sequencing (NGS). METHODS: ALTER-E-003, a single-arm, open-label phase II trial, enrolled patients with advanced ESCC across five Chinese centers. Patients received oral anlotinib 12 mg daily on days 1-14 per three-week cycle, with benmelstobart 1200 mg infused on day 1 of each cycle for up to 24 months. Thereafter, patients received anlotinib maintenance therapy. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), and safety. NGS and fluorescent multiplex immunohistochemistry (mIHC) were performed on tumor specimens. RESULTS: Of 53 screened patients, 46 completed the study. The confirmed ORR was 56.5% (95% CI 41.1-71.1), and DCR was 91.3% (95% CI 79.2-97.6). Median PFS was 15.74 months (95% CI 9.03-21.91). Treatment-related adverse events occurred in 93.5% of patients, with 28.3% experiencing grade 3 or higher events. NGS revealed a novel predictive mutational signature (TP53+/FAT1+/NOTCH3-) that was associated with better ORR (65.6% vers...