Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer

作者：Aditya Bardia, Xichun Hu, Rebecca Dent, Kan Yonemori, Carlos H. Barrios, Joyce O’Shaughnessy, Hans Wildiers, Jean‐Yves Pierga, Qingyuan Zhang, Cristina Saura, Laura Biganzoli, Joohyuk Sohn, Seock‐Ah Im, Christelle Lévy, William Jacot, Natasha Begbie, Jun Ke, Gargi Patel, Giuseppe Curigliano · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2407086 · 被引用次数：442 · 研究领域：HER2/EGFR in Cancer Research、Advanced Breast Cancer Therapies、Breast Cancer Treatment Studies

BACKGROUND: Outcomes in patients with hormone receptor-positive metastatic breast cancer worsen after one or more lines of endocrine-based therapy. Trastuzumab deruxtecan has shown efficacy in patients with metastatic breast cancer with low expression of human epidermal growth factor receptor 2 (HER2) after previous chemotherapy. METHODS: We conducted a phase 3, multicenter, open-label trial involving patients with hormone receptor-positive metastatic breast cancer with low HER2 expression (a score of 1+ or 2+ on immunohistochemical [IHC] analysis and negative results on in situ hybridization) or ultralow HER2 expression (IHC 0 with membrane staining) who had received one or more lines of endocrine-based therapy and no previous chemotherapy for metastatic breast cancer. Patients were randomly assigned in a 1:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival (according to blinded independent central review) among the patients with HER2-low disease. Secondary end points included progression-free survival among all the patients who had undergone randomization, overall survival, and safety. RESULTS: Of the 866 patients who underwent randomization, 713 had HER2-low disease, and 153 had HER2-ultralow disease. Among the patients with HER2-low disease, the median progression-free survival was 13.2 months (95% confidence interval [CI], 11.4 to 15.2) in the trastuzumab deruxtecan group and 8.1 months...