Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer

作者：Shanu Modi, Cristina Saura, Toshinari Yamashita, Yeon Hee Park, Sung‐Bae Kim, Kenji Tamura, Fabrice André, Hiroji Iwata, Yoshinori Ito, Junji Tsurutani, Joohyuk Sohn, Neelima Denduluri, Christophe Perrin, Kenjiro Aogi, Eriko Tokunaga, Seock‐Ah Im, Keun Seok Lee, Sara A. Hurvitz, Javier Cortés, Caleb Lee, Shuquan Chen, Lin Zhang, Javad Shahidi, Antoine Yver, Ian E. Krop · 发表于：New England Journal of Medicine · 年份：2019 · DOI：10.1056/nejmoa1914510 · 被引用次数：2020 · 研究领域：HER2/EGFR in Cancer Research、Protease and Inhibitor Mechanisms、Breast Lesions and Carcinomas

BACKGROUND: Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. In a phase 1 dose-finding study, a majority of the patients with advanced HER2-positive breast cancer had a response to trastuzumab deruxtecan (median response duration, 20.7 months). The efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab emtansine requires confirmation. METHODS: In this two-part, open-label, single-group, multicenter, phase 2 study, we evaluated trastuzumab deruxtecan in adults with pathologically documented HER2-positive metastatic breast cancer who had received previous treatment with trastuzumab emtansine. In the first part of the study, we evaluated three different doses of trastuzumab deruxtecan to establish a recommended dose; in the second part, we evaluated the efficacy and safety of the recommended dose. The primary end point was the objective response, according to independent central review. Key secondary end points were the disease-control rate, clinical-benefit rate, duration of response and progression-free survival, and safety. RESULTS: Overall, 184 patients who had undergone a median of six previous treatments received the recommended dose of trastuzumab deruxtecan (5.4 mg per kilogram of body weight). In the intention-to-treat analysis,...