The FDA expanded Gilead’s Trodelvy label in first-line triple-negative breast cancer, allowing use regardless of PD-L1 status and intensifying the TROP2 ADC competitive set. The new approval differentiates between patients ineligible for PD-1/L1 inhibitors versus those who are eligible, including combination use with Merck’s Keytruda for PD-L1–positive tumors. The update is grounded in Phase 3 outcomes from Ascent-03 and Ascent-04, with Trodelvy showing progression-free survival improvements and risk reductions versus chemotherapy and versus Keytruda-based combinations depending on subgroup. The agency decision also puts pressure on other first-line strategies, including Daiichi Sankyo/AstraZeneca’s Tropion-Breast program. For the ADC market, Trodelvy’s broader positioning may shift treatment selection and accelerate sequencing debates across line-of-therapy and biomarker testing protocols.