Massachusetts General Hospital Cancer Center, Harvard Medical School, Harvard University, Boston, MA, USA.
Breast Oncology Program, Inova Schar Cancer Institute, Fairfax, VA, USA.
Oncologist. 2022 Aug 5;27(8):637-645. doi: 10.1093/oncolo/oyac107.
The treatment of metastatic breast cancer (mBC) has evolved significantly in the past several years with the approval of new targeted agents. Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate with a topoisomerase I inhibitor payload, is a new addition to the class of therapies that target the human epidermal growth factor 2 (HER2) receptor. T-DXd was approved in the US in December 2019 for patients with HER2-positive metastatic or unresectable breast cancer who have received 2 or more prior anti-HER2-based regimens in the metastatic setting. In the DESTINY-Breast01 phase II trial (NCT03248492), T-DXd demonstrated high rates of durable responses in heavily pretreated patients with HER2-positive mBC, with a confirmed objective response rate of 62%, median duration of response of 18.2 months, and median progression-free survival of 19.4 months. In addition to efficacy, successful implementation of any new anticancer therapy includes learning how to prevent, monitor, and manage treatment-related adverse events. As T-DXd becomes more widely used, information can be gained from real-world clinical practices, institutional approaches, and the collaboration of multidisciplinary oncology teams who treat patients with T-DXd. This article reviews practical insights and management of nausea and vomiting, neutropenia, interstitial lung disease, risk of cardiotoxicity, and other adverse events associated with T-DXd administration from the perspective of health care providers who have experience utilizing T-DXd.
在过去的几年中，随着新的靶向药物的批准，转移性乳腺癌（mBC）的治疗发生了重大变化。曲妥珠单抗-美坦新偶联物（T-DXd）是一种新型的靶向人表皮生长因子 2（HER2）受体的治疗药物，它是一种抗体药物偶联物，带有拓扑异构酶 I 抑制剂有效载荷。T-DXd 于 2019 年 12 月在美国获得批准，用于接受过 2 种或更多种先前在转移性环境中基于抗 HER2 的方案治疗的 HER2 阳性转移性或不可切除乳腺癌患者。在 DESTINY-Breast01 期 II 期试验（NCT03248492）中，T-DXd 在 HER2 阳性 mBC 的大量预处理患者中显示出持久应答的高比率，确认的客观缓解率为 62%，中位缓解持续时间为 18.2 个月，中位无进展生存期为 19.4 个月。除了疗效之外，任何新的抗癌疗法的成功实施都包括学习如何预防、监测和管理与治疗相关的不良事件。随着 T-DXd 的应用越来越广泛，可以从真实世界的临床实践、机构方法以及治疗接受 T-DXd 治疗的患者的多学科肿瘤团队的协作中获得信息。本文从使用过 T-DXd 的医疗保健提供者的角度，综述了与 T-DXd 给药相关的恶心和呕吐、中性粒细胞减少、间质性肺病、心脏毒性风险和其他不良事件的实用见解和管理。
