Comparative results across phase III ASCENT-03 and TROPION-Breast02 showed that first-line TROP2-targeted antibody–drug conjugates improved progression-free survival versus standard chemotherapy in patients with immunotherapy-ineligible metastatic triple-negative breast cancer. The cross-trial analysis emphasizes consistent PFS advantages despite differences in study designs. This strengthens the clinical rationale for positioning TROP2 ADCs earlier in the treatment sequence for selected populations, where immunotherapy eligibility remains a key practical barrier. —