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)

Abstract

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.

Fig. 1. Time to treatment failure (TTF) for ADC1 and ADC2 with or without intervening therapy (IntTx).

A–D Double-headed Swimmer Plots demonstrating time on treatment in months for each antibody drug conjugates (ADC). Patients with HR + /HER2-low MBC are shown at left (A, B) and those with HR-/HER2-low MBC are shown at right (C, D). Patients receiving sacituzumab govitecan (SG, red) followed by trastuzumab deruxtecan (T-DXd, blue) are shown in the top row (A, C) and patients receiving T-DXd followed by SG are in the bottom row (B, D). For each tornado plot, each bar represents an individual patient. The time on treatment for the first ADC (ADC1) is shown at left, if the patient received an intervening therapy (InTx) the time on treatment is shown in green in the middle (with different shades of green representing subsequent lines of intervening therapy; if no green bar then the patient did not receive an intervening therapy), and the time on treatment for the second ADC (ADC2) is shown at right. Patients stopped ADC therapy due to progression unless otherwise noted as due to toxicity (X) or if they were still on therapy at the time of data cutoff (>).