Disitamab Vedotin plus Toripalimab in HER2-Expressing Advanced Urothelial Cancer

作者：Xinan Sheng, Gongqian Zeng, Cuijian Zhang, Qingyun Zhang, Jiasheng Bian, Haitao Niu, Jun Li, Yanxia Shi, Kai Yao, Bin Hu, Ziling Liu, Hong Liao, Zhixian Yu, Baiye Jin, Peng Zhao, Tiejun Yang, Xianling Liu, Qin Yang, Xueyi Xue, Xin Gou, Jian Huang, Jian Gu, Xiaolong Qi, Lu Zhang, Guoxian Ma, Beisong Liu, Jianmin Fang, Shusuan Jiang, Zhisong He, Aiping Zhou, Jun Guo · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2511648 · 被引用次数：87 · 研究领域：Bladder and Urothelial Cancer Treatments、Esophageal Cancer Research and Treatment、HER2/EGFR in Cancer Research

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate monotherapy has shown preliminary clinical efficacy in patients with chemotherapy-refractory HER2-positive locally advanced or metastatic urothelial cancer. Previous data showed promising antitumor activity and safety of HER2-specific disitamab vedotin as monotherapy and when combined with programmed cell death protein 1 (PD-1)-directed immunotherapy in this cancer. METHODS: In this phase 3, multicenter, open-label, randomized trial, we assigned patients with previously untreated HER2-expressing (immunohistochemical score of 1+, 2+, or 3+) locally advanced or metastatic urothelial cancer in a 1:1 ratio to receive either disitamab vedotin plus PD-1-specific toripalimab every 2 weeks or chemotherapy (gemcitabine plus cisplatin or carboplatin) every 3 weeks. The dual primary end points were progression-free survival (assessed by blinded independent review) and overall survival. Secondary end points included objective response and safety. Here we report the prespecified progression-free survival analysis and interim overall survival analysis. RESULTS: A total of 484 patients underwent randomization. The median follow-up was 18.2 months. Progression-free survival was significantly longer in the disitamab vedotin-toripalimab group than in the chemotherapy group (median, 13.1 vs. 6.5 months; hazard ratio for progression or death, 0.36; 95% confidence interval [CI], 0.28 to 0.46; P<0.001). Ov...