Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, Maryland.
Clin Cancer Res. 2021 Aug 15;27(16):4478-4485. doi: 10.1158/1078-0432.CCR-20-4557. Epub 2021 Mar 22.
On December 20, 2019, the FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki [DS-8201a; T-DXd; tradename ENHERTU (Daiichi Sankyo)] for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. Approval was based on data from study DS8201-A-U201 (DESTINY-Breast01) with supportive safety data from study DS8201-A-J101. The primary efficacy endpoint in DESTINY-Breast01 was overall response rate (ORR) based on confirmed responses by blinded independent central review (ICR) using RECIST v1.1 in all participants who were assigned to receive the recommended dose of 5.4 mg/kg while secondary endpoints included duration of response (DoR). The confirmed ORR based on ICR in these 184 patients was 60.3% [95% confidence interval (CI): 52.9-67.4] and the median DoR was 14.8 months (95% CI: 13.8-16.9). Interstitial lung disease, including pneumonitis, was experienced in patients treated with T-DXd and can be severe, life threatening, or fatal. In addition, neutropenia and left ventricular dysfunction were included as Warnings and Precautions in labeling. Other important common adverse reactions were nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, diarrhea, and thrombocytopenia. Overall, the totality of efficacy and safety data supported the accelerated approval of T-DXd for the intended indication.
2019 年 12 月 20 日，FDA 批准fam-trastuzumab deruxtecan-nxki [DS-8201a；T-DXd；商品名 ENHERTU（第一三共制药）]用于治疗不可切除或转移性 HER2 阳性乳腺癌的成年患者，这些患者在转移性环境中已接受过两种或多种先前的基于抗 HER2 的方案。批准基于 DS8201-A-U201（DESTINY-Breast01）研究的数据，该研究有来自 DS8201-A-J101 研究的支持安全性数据。DESTINY-Breast01 的主要疗效终点是所有接受推荐剂量 5.4mg/kg 的患者根据盲法独立中心审查（ICR）确认的反应计算的总缓解率（ORR），次要终点包括缓解持续时间（DoR）。这些 184 名患者的 ICR 确认 ORR 为 60.3%[95%置信区间（CI）：52.9-67.4]，中位 DoR 为 14.8 个月（95%CI：13.8-16.9）。接受 T-DXd 治疗的患者出现间质性肺病，包括肺炎，可能严重、危及生命或致命。此外，中性粒细胞减少和左心室功能障碍被列入标签中的警告和注意事项。其他重要的常见不良反应包括恶心、疲劳、呕吐、脱发、便秘、食欲下降、贫血、腹泻和血小板减少症。总的来说，疗效和安全性数据的整体情况支持加速批准 T-DXd 用于预期适应症。
