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.
Willing and able to provide signed informed consent approved by UBC/BC Cancer REB
Female or male patients, regardless of race and ethnic group, who are ≥18 years old at the time of informed consent
Patients with locally advanced or metastatic ER+/HER2 low (defined as IHC 1+ or 2+ but FISH or CISH negative by ratio as per ASCO/CAP guidelines) breast cancer. Patients with imaging confirmed inoperable locally advanced breast cancer for which treatment is palliative in intent are also permitted.
Prior treatment must have included prior endocrine based treatment in the metastatic setting in conjunction with a CDK4/6 inhibitor.
Patient is currently participating in any other type of medical research judged not to be scientifically or medically compatible with this study.
Patient has a known hypersensitivity to SG, irinotecan or its active metabolite SN-38.
Patients not available for follow up
Patients who are not willing to consider systemic treatment options
British Columbia Cancer Agency
Lead sponsor
Gilead Sciences
Collaborator