Abstract PS1-10-30: Real-world treatment utilization and outcomes of trastuzumab deruxtecan (T-DXd) among patients with hormone receptor-positive (HR+) HER2-low metastatic breast cancer (mBC) in the United States

Abstract Introduction: T-DXd, a HER2-directed antibody-drug conjugate, was the first treatment approved for patients (pts) with HER2-low (immunohistochemistry [IHC] 1+, IHC 2+ / in situ hybridization-negative [ISH−]) mBC, who had received a prior line of chemotherapy, based on the results from the Phase 3 trial, DESTINY-Breast04. This study describes demographic, clinical, and disease characteristics as well as real-world treatment outcomes of patients with HER2-low mBC treated with T-DXd, stratified by line of therapy (LOT) since mBC diagnosis. Methods: This was a retrospective longitudinal observational cohort study using patient-level electronic health record-derived de-identified data from the nationwide Flatiron Health database. Pts aged ≥18 years with no prior cancer (excluding thyroid and non-melanoma skin cancer), de-novo or recurrent HER2-low mBC diagnosed after Jan 1, 2018, who had received T-DXd between Aug 5, 2022 (FDA approval date), and Jan 1, 2025 (data cutoff), were eligible. Demographic and clinical characteristics were assessed at T-DXd initiation (index date). Descriptive statistics were used to explore pt characteristics, and the Kaplan-Meier (KM) method was used to analyze real-world time to next treatment (rwTTNT) and real-world time to treatment discontinuation (rwTTD). The overall median follow-up time was calculated using the reverse KM method. This analysis focuses on patients with HR+ mBC. Results: 1232 pts were included in the analysis; the overall median age at index date was 64.0 years. T-DXd was initiated as the first-line (1L), 2L, 3L, and ≥4L therapy following mBC diagnosis for 7.3% (n=90), 17.5% (n=216), 24.0% (n=296), and 51.1% (n=630) of pts, respectively. The reason for initiating T-DXd in 1L after mBC diagnosis (n=90) was not available. Pts who received T-DXd in earlier LOTs were more likely to be treated in a community versus academic setting and have recurrent disease (Table). Overall median follow-up time was 14.0 months. Median rwTTNT (95% CI) following the initiation of T-DXd as 1L, 2L, 3L, and ≥4L was 7.4 (5.0, 11.8), 9.7 (8.3, 11.3), 7.9 (6.7, 9.3), and 7.4 (6.6, 8.2) months, respectively. Median rwTTD (95% CI) for 1L, 2L, 3L, and ≥4L was 7.1 (5.0, 11.8), 9.3 (8.3, 10.7), 7.8 (6.5, 9.2), and 7.1 (6.4, 7.8) months, respectively. Conclusion: Except for patients with HR+ HER2-low mBC who initiated T-DXd in 1L after mBC diagnosis, a trend was observed toward worse outcomes (as indicated by shorter rwTTNT and rwTTD) in pts who initiated T-DXd in later lines. Further study is warranted as these results suggest earlier initiation of T-DXd for eligible pts with HR+ HER2-low mBC (in accordance with approved labels) prolongs duration of disease control. Citation Format: A. Brufsky, P. A. Kaufman, M. Inoue-Choi, C. Lam, C. Nordon, E. John, L. Luo, H. Rugo. Real-world treatment utilization and outcomes of trastuzumab deruxtecan (T-DXd) among patients with hormone receptor-positive (HR+) HER2-low metastatic breast cancer (mBC) in the United States [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-10-30.