Genomic and Transcriptomic Predictors of Sequential SG Sensitivity After T-DXd in ER+/HER2-Low Metastatic Breast Cancer

Advanced hormone positive (HR+), HER2 negative breast cancer continues to pose a challenge when patients have progressed on CDK4/6 inhibitor and endocrine therapy leaving limited treatment options. Antibody-drug conjugates (ADCs) such as sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have changed practice due to significant improvement in progression free survival (PFS) and overall survival (OS) seen in this disease setting. There is a genuine interest to use SG sequentially after T-DXd, however there is no current prospectively curated evidence to support this strategy. Though the epitope is different, the payload are both topoisomerase I inhibitors. Thus, evidence is needed of both clinical efficacy and identification of mechanisms of sensitivity and resistance to sequential ADCs in HER-2 low MBC. It is hypothesized that performing whole genome and whole transcriptome sequencing in fresh tumour biopsies post progression of T-DXd and prior to SG in ER+/HER2 low metastatic breast cancer (MBC) will provide mechanistic insights into identifying biomarkers, and thus patients, sensitive to sequential SG.

This description comes directly from the study's public registry record.

Stephen Chia, MD  ·  604-877-6000  ·  schia@bccancer.bc.ca

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