Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer

作者：Shanu Modi, William Jacot, Toshinari Yamashita, Joohyuk Sohn, María Vidal, Eriko Tokunaga, Junji Tsurutani, Naoto Tada Ueno, Aleix Prat, Yee Soo Chae, Keun Seok Lee, Naoki Niikura, Yeon Hee Park, Binghe Xu, Xiaojia Wang, Miguel Gil‐Gil, Wěi Li, Jean‐Yves Pierga, Seock‐Ah Im, Halle C. F. Moore, Hope S. Rugo, Rinat Yerushalmi, Flora Zagouri, Andrea Gombos, Sung‐Bae Kim, Qiang Liu, Ting L. Luo, Cristina Saura, Peter Schmid, Tao Sun, Dhiraj Gambhire, Lotus Yung, Yibin Wang, Jasmeet Chadha Singh, Patrik Vitazka, Gerold Meinhardt, Nadia Harbeck, David Cameron · 发表于：New England Journal of Medicine · 年份：2022 · DOI：10.1056/nejmoa2203690 · 被引用次数：2701 · 研究领域：HER2/EGFR in Cancer Research、Breast Cancer Treatment Studies、Cancer Treatment and Pharmacology

BACKGROUND: Among breast cancers without human epidermal growth factor receptor 2 (HER2) amplification, overexpression, or both, a large proportion express low levels of HER2 that may be targetable. Currently available HER2-directed therapies have been ineffective in patients with these "HER2-low" cancers. METHODS: We conducted a phase 3 trial involving patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy. (Low expression of HER2 was defined as a score of 1+ on immunohistochemical [IHC] analysis or as an IHC score of 2+ and negative results on in situ hybridization.) Patients were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival in the hormone receptor-positive cohort. The key secondary end points were progression-free survival among all patients and overall survival in the hormone receptor-positive cohort and among all patients. RESULTS: Of 557 patients who underwent randomization, 494 (88.7%) had hormone receptor-positive disease and 63 (11.3%) had hormone receptor-negative disease. In the hormone receptor-positive cohort, the median progression-free survival was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician's choice group (hazard ratio for disease progression or death, 0.51; P<0.001), and overall survival was 23.9 months and 17.5 months, respectively (hazard ratio for death, ...