Abstract PS2-04-27: Real-world Clinical Outcomes of Trastuzumab Deruxtecan Among HER2+ Metastatic Breast Cancer Patients with and without Brain Metastases: Data from U.S Community Oncology Practices

Abstract Background: Trastuzumab deruxtecan (T-DXd) was initially approved by the FDA for treatment of patients with HER2+ unresectable or metastatic breast cancer (mBC) with two or more prior anti-HER2 regimens (3L+) in 12/2019 and subsequently approved among patients with one prior anti-HER2 regimen (2L) in 5/2022. Clinical trials including DESTINY-Breast12 have demonstrated substantial and durable activity of T-DXd overall, and within the central nervous system, in patients with active and stable brain metastasis (BM). However, limited data exists regarding the intracranial activity and real-world clinical benefit associated with T-DXd in this patient population. This study examined clinical outcomes among patients with HER2+ mBC, with and without active or stable BMs, who were treated with T-DXd in the community oncology setting. Methods: This retrospective cohort study used deeply-curated electronic medical record data from practices affiliated with ONCare Alliance. A total of 300 adult patients with mBC diagnosis, confirmed HER2+ status, who received T-DXd in the 2L or later setting anytime from 01/2020 to 08/2024 were selected for chart abstraction. Patient demographic characteristics, clinical characteristics, and comorbidities were assessed descriptively, and compared with chi-square or Fisher exact tests. Clinical outcomes, including real-world time to treatment failure (rwTTF) and real-world progression-free survival (rwPFS), were assessed using Kaplan-Meier median and confidence interval estimates. All analyses were stratified by BM vs. no BM status and active (new or worsening) vs. stable (unchanged or improving) BM status. Results: Of 300 patients, 95 patients (68 active BMs and 27 stable BMs) had BMs at initiation of T-DXd. Overall, the median follow-up period was 17.0 months, mean age was 59.3 years (±12.6) and a majority were White (82.3%), post-menopausal (76.3%) and had an ECOG score of 0-1 (80.3%). The baseline patient demographic and clinical characteristics were generally similar among patients with vs. without BM, except for age (mean 54.0 vs. 61.7 years, p 0.001), HR status (HR+ 55.8% vs. 68.3%, p = 0.0355) and comorbidity index (mean 0.28 vs. 0.68, p 0.001). No statistically significant differences in baseline demographics and clinical characteristics were observed between active vs. stable BM patients. No significant differences in clinical outcomes were observed between BM vs. no BM cohorts (median rwTTF was 10.0 95% CI 8.1 - 12.5 vs. 11.1 months 9.0 - 12.6, p = 0.3507; and median rwPFS was 12.1 8.6 - 14.2 vs. 13.5 months 11.8- 14.91, p = 0.2483). Similarly, no significant differences in clinical outcomes were observed between active vs. stable BM cohorts (median rwTTF was 11.3 8.3 - 12.9 vs. 8.1 months 4.3 - 14.6, p = 0.9679; and median rwPFS was 12.1 8.9 - 14.2 vs. 10.6 months 5.5 - 23.7, p = 0.4140). Conclusion: This study is among the largest real-world data studies characterizing the clinical effectiveness of T-DXd among HER2+ mBC patients with vs. without brain metastasis and among patient segments with active vs. stable status. Results support the effectiveness of T-DXd in patients with brain metastasis, and showed no difference in outcomes based on active vs. stable status. Findings from this study reinforce the value of utilizing T-DXd to improve long-term outcomes of all patients with HER2+ mBC, irrespective of the presence of BM or active vs. stable brain metastasis. Citation Format: S. Mehta1, H. Neuhalfen2, A. Peevyhouse2, D. Adhikari2, C. Williams2, M. Garretson1, S. Blau2, M. Walker2. Real-world Clinical Outcomes of Trastuzumab Deruxtecan Among HER2+ Metastatic Breast Cancer Patients with and without Brain Metastases: Data from U.S Community Oncology 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 PS2-04-27.