Abstract Background: A novel antibody drug conjugate, trastuzumab deruxtecan (T-DXd), has demonstrated unparalleled clinical benefit in DESTINY-Breast clinical trials for HER2+ metastatic breast cancer (mBC). However, limited data exists on the clinical benefit of T-DXd in minority racial/ethnic patient groups in the US. This study assessed real-world patient characteristics, treatment patterns, and outcomes among patients (pts) with HER2+ mBC treated with T-DXd in the US community oncology setting by racial/ethnic group. Methods: This retrospective chart review study utilized the iKnowMed electronic health record and included pts who initiated T-DXd for HER2+ mBC (index event) between Jan 1, 2020 and Apr 30, 2024, had ≥1 post-index visit and had documented race/ethnicity as Black and/or Hispanic (BH cohort) or White and non-Hispanic (Wt cohort). Pts were followed until last patient contact or death on or before Apr 30, 2024. To balance key baseline characteristics across cohorts, BH pts were propensity score matched to Wt pts with exact matching according to line of therapy (LOT), adjustment for age category, and a caliper width of 0.25 standard deviations. Patient characteristics, treatment patterns, real-world Objective Response Rate (rwORR, complete/partial response) and incidence of adverse events of interest while on treatment were summarized descriptively for both cohorts. Time to treatment discontinuation (TTD), time to next treatment (TTNT), and real-world progression-free survival (rwPFS) from index were estimated using the Kaplan-Meier method. Results: A total of 162 pts were included, with 81 in each cohort. Mean age at index was 56.3 years (BH 56.3; Wt 56.2) and all pts all were female except for 1 BH male. A higher proportion of pts in the BH cohort were residing in the South region (59.3% vs. 37.0%), had visceral only metastasis (65.4% vs. 58.0%) and HR- status (27.2% vs. 22.2%) than in the Wt cohort. More pts in the BH cohort (49.4%) received T-DXd in 3L+ setting than in the Wt cohort (43.2%). The rwORR was 63.0% and 67.9% in the BH and Wt cohort, respectively. Among the BH pts (median follow-up: 15.2 months mo), median (95% CI) rwPFS was 16.6 mo (9.9-21.4), TTD was 12.5 mo (9.7-14.9), and TTNT was 18.3 mo (13.1-22.9). Similarly, among Wt pts (median follow-up: 13.6 mo), median (95% CI) rwPFS was 14.7 mo (9.8-17.4), TTD was 12.2 mo (9.7-16.8), and TTNT was 18.4 mo (13.2-21.1). The rates of adverse events of interest were as follows: nausea (BH 50.6%; Wt 70.4%), fatigue (BH 45.7%; Wt 64.2%), vomiting (BH 21.0%; Wt 27.2%), diarrhea (BH 24.7%; Wt 35.8%), neutropenia (BH 13.6%; Wt 7.4%), alopecia (BH 2.5%; Wt 11.1%), and interstitial lung disease/pneumonitis (BH 7.4%; Wt 4.9%). During follow-up, 30.9% of BH pts and 33.3% of Wt pts initiated subsequent treatment beyond index. Among these pts (BH n = 25; Wt n = 27), trastuzumab emtansine-based (BH 16.0%; Wt 18.5%) and T-DXd-based (BH 16.0%; Wt 14.8%) regimens were most frequently used in the LOT immediately following index. Conclusion: Among US minority racial/ethnic groups (Blacks and/or Hispanics) under-represented in prior HER2+ mBC clinical studies, T-DXd demonstrated real-world clinical benefit and tolerability similar to that observed in White non-Hispanic pts. Interpretation of findings should consider limitations inherent to the retrospective design, including residual and unmeasured confounding, and potential information bias stemming from differential symptom reporting, clinical monitoring, and documentation practices across racial/ethnic groups. Nonetheless, these findings support the effectiveness of T-DXd across diverse populations and underscore the importance of inclusive data to inform clinical decision-making and advance equitable breast cancer management and care delivery across racial/ethnic groups. Citation Format: S. Mehta, L. Stevens, R. Shah, M. Garretson, S. Pasha, C. Brown-Bickerstaff, L. Herms, M. Danso. Real-world effectiveness of trastuzumab deruxtecan in HER2+ metastatic breast cancer by racial and ethnic group - Data from US community practices 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 PS5-01-15.
Mehta et al. (2026) studied this question.