Abstract P2-12-20: A Real-World Study of the Effectiveness and Safety of Trastuzumab Deruxtecan (T-DXd) in HER2-low Metastatic Breast Cancer (mBC) among Racial and Ethnic Minorities and Older Populations in the United States

Abstract Background: Approximately 45-55% of all primary breast cancer (BC) cases are classified as human epidermal growth factor receptor 2 low (HER2-low). Currently, trastuzumab deruxtecan (T-DXd) is the only approved HER2-targeted therapy for HER2-low metastatic BC (mBC). In the US, Black/African-American and Hispanic women have more advanced BC stage at diagnosis, less favorable tumor characteristics, and a lower chance of receiving guideline concordant care compared to non-Hispanic white women. Similarly, women ≥65 years of age have higher BC incidence and mortality, are more likely to be under-treated, and are less likely to comply with treatment compared to younger women. Given these health inequities, we sought to further evaluate the safety and effectiveness of T-DXd among racial/ethnic minorities and older patients in the HER2-low mBC setting. Specific Aims: The primary objective of this study is to assess the effectiveness of T-DXd measured by real-world progression-free survival among HER2-low mBC patients treated with T-DXd, stratified by race, ethnicity, and age group. Secondary objectives are twofold: (1) describe demographic/clinical characteristics and prior anticancer therapy among HER2-low mBC patients and (2) assess the real-world targeted safety profile of T-DXd among HER2-low mBC patients, both stratified by race, ethnicity, and age group. Targeted adverse events (TAEs) include interstitial lung disease/pneumonitis, left ventricular dysfunction, neutropenia/febrile neutropenia, and nausea/vomiting. As an exploratory objective, we will assess the effectiveness of T-DXd using additional endpoints including real-world overall survival, real-world time to next treatment, and real-world time to treatment discontinuation. Eligibility criteria: To be included in the Source Population, patients must be ≥18 years old with HER2-low mBC. Major exclusion criteria include history of a non-BC primary cancer, history of HER2 positive disease, and having neither race nor ethnicity data. The T-DXd Treated Cohort will include the subgroup of patients from the Source Population who receive T-DXd during the study period. Study Design: This is a non-interventional, retrospective cohort study conducted in the real-world setting. The data source is the Guardian Research Network (GRN), a de-identified electronic medical record database covering US oncology and non-oncology care. The planned study period is from August 2022 to December 2026. All necessary variables will be obtained from structured data elements or curation of unstructured data elements, as needed (e.g., physician notes, radiology reports). Present and target accrual. A sample size projection for the T-DXd Treated Cohort was completed based on current patient accrual in GRN with assumptions for T-DXd uptake. At the time of this analysis, 60 patients fulfilled all eligibility criteria for inclusion in the T-DXd Treated Cohort, and approximately 450 patients are projected to be eligible for inclusion in this cohort through the end of the study period. Statistical Methods: All analyses will be descriptive; no hypothesis testing is planned. The Source Population will be used to summarize demographics, clinical characteristics, and treatment patterns. Effectiveness endpoints will be analyzed using a time-to-event approach (Kaplan-Meier estimator). The proportion of patients with each TAE will be summarized and select TAE characteristics will be described. All analyses will be conducted overall and stratified by race, ethnicity, and age group (≤65, >65, and >75 years). Citation Format: Mackenzie Henderson, Candice Drinkwater, Danielle Potter, Divi Alagappan, Victoria de Giorgio-Miller, Shahid Ashfaque, Gargi Patel, Kellie Ryan, Cecilia Orbegoso Aguilar, Armen A. Ghazarian. A Real-World Study of the Effectiveness and Safety of Trastuzumab Deruxtecan (T-DXd) in HER2-low Metastatic Breast Cancer (mBC) among Racial and Ethnic Minorities and Older Populations in the United States [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-12-20.