Evaluation of efficacy and safety of sequential antibody drug conjugates (ADCs) in human epidermal growth factor 2 (HER2)-negative metastatic breast cancer

Limited data is available assessing sequencing of antibody drug conjugates (ADCs) in patients with hormone receptor-positive (HR +), human epidermal growth factor 2 (HER2)-negative, HER2-low, and triple-negative metastatic breast cancer (MBC), including patients with brain metastases (BrM) or leptomeningeal disease (LMD). This study assesses the efficacy and safety of sequential sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) in MBC and impact on chemotherapy (CTX). This is a single-center, retrospective, cohort study in adult patients with HR + , HER2-negative, or low MBC who received T-DXd and/or SG. A total of 112 patients were divided into three cohorts: ADCs given sequentially (cohort A), ADC then CTX (cohort B), or CTX between ADCs (cohort C). The median progression-free survival (mPFS) in cohort A was 4.5 months for SG before T-DXd and 3.1 months for T-DXd before SG. In cohort B, mPFS was 3.1 months for CTX following T-DXd. For CTX following SG, mPFS for CTX was 2.5 months. In patients who received both ADCs, PFS was 2.1 months. In cohort C, mPFS for SG following T-DXd and CTX was 2.1 months and 3.3 months for T-DXd following SG and CTX. The mPFS for ADC1 was longer than ADC2 (5.5 months SG, 3.4 months T-DXd). Those with BrM and/or LMD demonstrated stable disease. Sequential administration of ADCs results in a shorter PFS. CTX efficacy is impacted by prior ADC administration. Outcomes for patients with BrM and LMD do not differ for those without recurrence to the brain.