Datopotamab deruxtecan: a new era in targeted therapy for metastatic breast cancer

Datopotamab deruxtecan (Datroway) is approved by the FDA to treat hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that is metastatic or incurable. This antibody-drug combination consists of a linker, the cytotoxic compound DXd, and a monoclonal antibody (mAb) that targets TROP2. Following internalization facilitated by the mAb's binding to TROP2 on cancer cells, DXd is released, causing cell death. Dato-DXd outperformed traditional chemotherapy in the TROPION-Breast01 study. With better efficacy than conventional treatments, it offers a possible alternative for individuals who have not responded to previous endocrine or chemotherapy therapies. This manuscript reviews the mechanisms of action, clinical efficacy, safety profiles, and trials of Dato-DXd and T-DXd, highlighting their transformative potential and positioning in current breast cancer treatment algorithms.