Exploring DESTINY: the Past, Present, and Future of Trastuzumab Deruxtecan

Purpose of Review HER2-positive breast cancer accounts for 10–15% of all breast cancers and fam-trastuzumab deruxtecan (T-DXd) has played a major role in moving the treatment of HER2-expressing disease forward. Recent Findings T-DXd is a novel antibody–drug conjugate (ADC) composed of a humanized IgG1 monoclonal antibody against HER2 receptor bound to a potent topoisomerase I cytotoxin payload by a cleavable peptide linker. It has been shown to have robust preclinical activity in pretreated cancer cell lines, as well as meaningful clinical activity in advanced HER2-expressing breast cancer. Recent studies have demonstrated T-DXd as an active agent for metastatic HER2-positive patients, and as a viable additional line for heavily pretreated patients with HER2-low disease. The toxicity of T-DXd remains manageable and burden of side effects seems to be lower when offered as an earlier line of therapy over the course of treatment. Summary In this review, we discuss the pharmacology of T-DXd, review pertinent preclinical and clinical data, and address potential challenges and future directions related to the use of T-DXd in clinical practice.