Department of Medicine I, Division of Oncology, Medical University of Vienna , Vienna, Austria.
Comprehensive Cancer Center Vienna , Wien, Austria.
Expert Opin Investig Drugs. 2020 Sep;29(9):901-910. doi: 10.1080/13543784.2020.1792443. Epub 2020 Jul 23.
The prognosis of patients with HER2-positive breast cancer was dramatically changed by the introduction of targeted therapies. With trastuzumab, pertuzumab, and T-DM1 widely used as (neo)adjuvant therapy today, novel treatment options are required to optimize treatment of HER2-positive metastatic disease. Trastuzumab-deruxtecan is an antibody-drug conjugate (ADC) consisting of a monoclonal humanized immunoglobulin G1 antibody, a linker molecule, and the exatecan derivative DXd. T-DXd has a higher drug to antibody ratio compared with T-DM1; in addition, membrane permeability of DXd is high, resulting in an increased bystander effect. Results from early clinical development suggest a clinically relevant activity of T-DXd in heavily pretreated patients with HER2-positive metastatic breast cancer progressing on T-DM1. Interstitial lung disease was a side-effect requiring special attention and was observed in approximately 13% of patients.
This article reviews preclinical and clinical data on T-DXd. A systematic literature search was performed to identify relevant publications. The search included original research articles, abstracts from major conferences, and reviews and was limited to English-language publications.
T-DXd is an efficacious and tolerable drug and harbors promise as a key addition to the therapeutic field in HER2-positive breast cancer.
曲妥珠单抗、帕妥珠单抗和 T-DM1 的问世极大地改变了 HER2 阳性乳腺癌患者的预后。如今，这些药物已广泛用于新辅助和辅助治疗，因此需要新的治疗方案来优化 HER2 阳性转移性疾病的治疗。曲妥珠单抗-德鲁替康是一种抗体药物偶联物（ADC），由单克隆人源化 IgG1 抗体、连接子分子和依喜替康衍生物 DXd 组成。与 T-DM1 相比，T-DXd 的药物抗体比（DAR）更高；此外，DXd 的膜通透性较高，导致旁观者效应增加。早期临床开发结果表明，在接受过 T-DM1 治疗后进展的 HER2 阳性转移性乳腺癌的重度预处理患者中，T-DXd 具有临床相关的活性。间质性肺病是一种需要特别注意的副作用，约 13%的患者观察到这种副作用。
本文综述了 T-DXd 的临床前和临床数据。系统地检索了相关文献，包括原始研究文章、主要会议的摘要以及综述，并仅限于英文出版物。
T-DXd 是一种有效且耐受良好的药物，有望成为 HER2 阳性乳腺癌治疗领域的重要补充。
