Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer

作者：Sibylle Loibl, Yeon Hee Park, Zhi‐Ming Shao, Chiun‐Sheng Huang, Carlos Barrios, Jame Abraham, Aleix Prat, Naoki Niikura, Seock-Ah Im, Wěi Li, Huiping Li, Yongsheng Wang, Herui Yao, Sung-Bae Kim, Cuizhi Geng, Wuilbert Rodríguez Pantigoso, Francisco Javier Ramírez Godinez, Chuangui Song, Yuan Ching Chang, Augusto Antoniazzi, Shin‐Cheh Chen, Zhigao Li, Zbigniew Nowecki, Joline S.J. Lim, Elton Mathias, Yuta Sato, Wenjing Lu, Hanan Abdel‐Monem, M. Untch, Charles E. Geyer · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2514661 · 被引用次数：47 · 研究领域：HER2/EGFR in Cancer Research、Breast Cancer Treatment Studies、Advanced Breast Cancer Therapies

BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer and residual disease after neoadjuvant therapy are at high risk for recurrence. METHODS: In a phase 3, open-label, international, randomized trial, we investigated postneoadjuvant trastuzumab deruxtecan (T-DXd; 5.4 mg per kilogram of body weight) as compared with trastuzumab emtansine (T-DM1; 3.6 mg per kilogram), the current standard treatment, in patients with HER2-positive breast cancer with residual invasive disease and node-positive disease at surgery or inoperable disease at diagnosis. The primary end point was invasive disease-free survival, and the key secondary end point was disease-free survival (including survival free from noninvasive breast cancers and second primary nonbreast cancers). Other end points included overall survival, distant recurrence-free interval, brain metastasis-free interval, and safety. RESULTS: A total of 1635 patients were randomly assigned (in a 1:1 ratio) to receive T-DXd (818 patients) or T-DM1 (817 patients). At the data-cutoff date, the median duration of follow-up was approximately 30 months in each group. Invasive-disease events or deaths were reported in 51 patients (6.2%) in the T-DXd group and 102 patients (12.5%) in the T-DM1 group (hazard ratio, 0.47; 95% confidence interval [CI], 0.34 to 0.66; P<0.001); 3-year invasive disease-free survival was 92.4% and 83.7%, respectively. Invasive-disease events, noninvasive-disease events, ...