FDA approved datopotamab deruxtecan (Datroway; Dato-DXd) as a first-line option for a defined subset of triple-negative breast cancer, extending the use of TROP2-directed antibody-drug conjugates beyond later lines. The decision is based on phase 3 TROPION-Breast02 data in adults who are not candidates for PD-1/PD-L1 inhibitor therapy. In the trial, Dato-DXd improved median overall survival to 23.7 months versus 18.7 months with investigator’s choice chemotherapy (HR 0.79; P=.0290). Progression-free survival also increased to 10.8 months from 5.6 months, alongside a higher objective response rate (64% vs 30%). The approval may reshape treatment sequencing in TNBC by expanding ADC coverage for patients who cannot receive immunotherapy, potentially influencing guideline adoption and clinician prescribing patterns.