Sequential Cytotoxic Payloads Against Metastatic Breast Cancer

The use of antibody-drug conjugates (ADCs, wherein an antitumor antibody is linked to a cytotoxic payload) has improved outcomes across many tumor types. For the three ADCs thus far approved in the setting of breast cancer, the payload is a topoisomerase 1 inhibitor: trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), or datopotamab deruxtecan. T-DXd is used for HER2-positive metastatic breast cancer as well as HER2-low and HER2-ultralow disease (including endocrine-refractory disease).

Are ADCs for breast cancer especially beneficial if used in sequence (with T-DXd used most often as the initial agent)? Investigators conducted a retrospective observational study of a database spanning 280 U.S. clinics. Patients who received T-DXd and at least one additional non–T-DXd therapy between 2019 and 2023 were included, and tumors were defined as HER2-positive, HER2-low, or HER2-0 based on the most recent biopsy. The primary endpoint was real-world PFS (rwPFS).

Key Results

A total of 793 patients were identified who had received another line of systemic therapy after discontinuing T-DXd, most often because of disease progression. Tumor types were HER2-positive (54%), ER-positive/HER2-negative (37%), and triple negative (~10%). Across all patients and subtypes, after adjustment for prior lines of treatment, treatment with SG after T-DXd was associated with shorter rwPFS relative to the other regimens (3.4 months vs. 5.0 months).