Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer

作者：Sara M. Tolaney, Zefei Jiang, Qingyuan Zhang, Romualdo Barroso‐Sousa, Yeon Hee Park, Mothaffar F. Rimawi, Cristina Saura, Andreas Schneeweiß, Masakazu Toi, Yee Soo Chae, Yasemi̇n Kemal, Mukesh Chaudhari, Mehmet Alı Nahıt Şendur, Toshinari Yamashita, M.L. Casalnuovo, Michael A. Danso, Jie Liu, Jagdish Shetty, Pia Herbolsheimer, Sibylle Loibl · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2508668 · 被引用次数：55 · 研究领域：HER2/EGFR in Cancer Research、Cancer Treatment and Pharmacology、Advanced Breast Cancer Therapies

BACKGROUND: Trastuzumab deruxtecan has shown efficacy in patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic breast cancer. The efficacy and safety of trastuzumab deruxtecan in patients with no previous therapy for HER2-positive advanced or metastatic breast cancer are unclear. METHODS: We conducted a phase 3 trial involving patients with HER2-positive advanced or metastatic breast cancer and no previous chemotherapy or HER2-directed therapy for metastatic disease. Patients were randomly assigned in a 1:1:1 ratio to receive trastuzumab deruxtecan plus pertuzumab; trastuzumab deruxtecan plus placebo; or a taxane, trastuzumab, and pertuzumab (THP). The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included objective response, duration of response, and safety. RESULTS: For this prespecified interim analysis, data for trastuzumab deruxtecan plus pertuzumab and for THP are reported; data for trastuzumab deruxtecan plus placebo remain blinded until the final analysis of progression-free survival. At the data-cutoff date (February 26, 2025), the median progression-free survival was 40.7 months with trastuzumab deruxtecan plus pertuzumab (383 patients) and 26.9 months with THP (387 patients) (hazard ratio for progression or death, 0.56; 95% confidence interval [CI], 0.44 to 0.71; P<0.00001 [P-value boundary for superiority, 0.00043]). The incidence of...