Multicenter retrospective cohort study of the sequential use of the antibody-drug conjugates (ADCs) trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) in patients with HER2-low metastatic breast cancer (MBC).

Antibody drug conjugates (ADCs) have improved outcomes for patients with metastatic breast cancer (MBC), but there is little data about the sequential use of these agents. In this multicenter retrospective cohort study, we identified 84 patients with HER2-low MBC treated sequentially with trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) in either order at 5 institutions between 2020-2024. We evaluated clinical parameters associated with time to treatment failure (TTF) and real-world overall survival (rwOS). Median TTF was longer for ADC1 than ADC2, irrespective of HR-status, ADC sequence order, age ≤65 or >65 years, presence of visceral disease, or use of an intervening therapy. Younger age, longer time from MBC diagnosis to start of ADC1, and receipt of SG as ADC1 were associated with longer rwOS from start of ADC1. This cohort represents one of the first multicenter retrospective series of patients treated with sequential ADCs for HER2-low MBC, which may inform clinical practice.