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

Poster Abstract:

Background:
Antibody drug conjugates (ADCs) are composed of a monoclonal antibody with a cytotoxic payload designed to deliver targeted therapy with minimal damage to surrounding cells.1 Recent trials of ADCs in the metastatic breast cancer (MBC) setting have demonstrated significantly improved survival outcomes.2-5 As a result, sacituzumab govitecan and trastuzumab deruxtecan have been FDA approved in adult patients with hormone receptor positive (HR+), human epidermal growth factor 2 (HER2) negative, HER2-low, and triple negative MBC. Patients are now eligible to receive several lines of therapy with ADCs. With the increased development of ADCs that share similar targets and cytotoxics with similar mechanisms of action, little is known regarding acquired resistance and impact on subsequent lines of therapy. There is limited data available assessing the efficacy, safety, and optimal sequencing of ADCs in this setting or in patients with brain metastases or leptomeningeal disease (LMD). Recent multicenter retrospective data suggests a reduction in response rates with subsequent ADC treatment in patients with MBC. This retrospective study aims to assess the efficacy, safety, and tolerability of sequential ADCs in the metastatic breast cancer setting in both intracranial and extracranial disease and to determine if the efficacy of sequential cytotoxic chemotherapy may be impacted by ADC use.

Objectives
The primary objective is to evaluate the time to progression of sequential ADCs (sacituzumab govitecan and trastuzumab deruxtecan) in HER2- metastatic breast cancer as well as subsequent lines of conventional cytotoxic therapy following progression on ADC. The secondary objectives are to assess intracranial and extracranial response in patients with brain metastases and LMD, evaluate the time to progression and safety of sacituzumab govitecan and trastuzumab detruxtecan, and safety of sequential ADCs sacituzumab govitecan and trastuzumab deruxtecan in HER2- metastatic breast cancer.

Methods
This single-center, retrospective, cohort study will assess the efficacy, safety, and tolerability of sequential ADCs in HER2 negative metastatic breast cancer patients at Duke Cancer Institute (DCI). Adult patients ≥ 18 years of age with a diagnosis of HR+, HER2 low or triple-negative advanced/metastatic breast cancer that have received trastuzumab-deruxtecan and/or sacituzumab govitecan between April 2021 to October 2023 at the DCI (Duke Cancer Center, Macon Pond and Duke Regional Satellite sites) were included. Patients that did not receive prescribed therapy within the DCI sites and were managed locally were excluded. Kaplan-Meier curves and estimates were used to describe the time until progression/death event and progression/death progression-free survival rates.

Results: Pending

Discussion/conclusions: Pending

References (must also be included in final poster): 1. Chau CH, Steeg PS, Figg WD. Antibody-drug conjugates for cancer. Lancet. 2019;394(10200):793-804. doi:10.1016/S0140-6736(19)31774-X
2. Modi S, Jacot W, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690
3. Rugo HS, Bardia A, Tolaney SM, et al. TROPiCS-02: A Phase III study investigating sacituzumab govitecan in the treatment of HR+/HER2- metastatic breast cancer. Future Oncol. 2020;16(12):705-715. doi:10.2217/fon-2020-0163
4. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021;384(16):1529-1541. doi:10.1056/NEJMoa2028485
5. Modi S, Saura C, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2020;382(7):610-621. doi:10.1056/NEJMoa1914510