Real-world treatment patterns and outcomes in HER2-positive metastatic breast cancer patients with brain metastases.

e13022 Background: The treatment paradigm for HER2+ metastatic breast cancer (MBC) patients with brain metastases (BM) has shifted from local therapies to a multi-disciplinary approach including CNS-penetrating, HER2 targeted systemic therapies. First line systemic therapy for HER2+ MBC is trastuzumab (H), pertuzumab (P) and Taxol (T). Subsequent therapies include trastuzumab emtansine (T-DM1), tucatinib/H/capecitabine triplet therapy (TUC) and trastuzumab deruxtecan (T-DXd). This study aimed to examine real-world treatment patterns and clinical outcomes of HER2+ breast cancer BM. Methods: This single institution retrospective study included HER2+ MBC patients with de novo or metachronous BM treated between Jan 2017 - Jul 2024. Primary objective was to evaluate patterns of care after BM diagnosis. Overall survival (OS) was defined from BM diagnosis date to death. Systemic progression-free survival (PFS) and CNS-PFS were defined from systemic therapy initiation date to systemic or CNS progression, respectively, or death. Kaplan-Meier method was used for survival analysis. Radiation necrosis (RN) was diagnosed by perfusion MRI +/- pathology. Results: Ninety patients met criteria, including 37 (41.1%) with de novo BM at MBC diagnosis and 53 (58.9%) diagnosed after MBC diagnosis. Median number of BMs at diagnosis was 2 (range 1-40) and median total BM volume was 7.41 (range 0.09-105.22) cm 3 . Eighty-four (93.3%) patients received stereotactic radiosurgery (SRS); 27 (30.0%), WBRT; and 46 (51.1%), neurosurgery. Of 140 total SRS courses received, 43 (30.7%) were 18-22 Gy in 1 fraction (fxn); 74 (52.9%), 21-24 Gy in 3 fxns; and 18 (12.9%), 25-30 Gy in 5 fxns. For patients diagnosed with BM before 2020 (n = 46), the 1 st systemic therapy prescribed was HPT (n = 6; 13.0%), T-DM1 (n = 9; 19.6%), TUC (n = 1; 2.2%) or other (n = 30; 65.2%). Since 2020 (n = 44), the 1 st systemic therapy prescribed was HPT (n = 4; 9.1%), T-DM1 (n = 3; 6.8%), TUC (n = 10; 22.7%), T-DXd (n = 9; 20.5%) or other (n = 18; 40.9%). The median duration for each systemic therapy was 5.8 mo, 9.5 mo, 10.6 mo and 4.0 mo for T-DM1, TUC, T-DXd and other treatments, respectively (p = 0.21). For the entire cohort, median OS was 42.4 mo (95% CI 23.0-83.0), median systemic PFS was 13.7 mo (95% CI 11.8-16.3) and median CNS-PFS was 14.9 mo (95% CI 11.5-25.1). Twenty-three (25.6%) patients developed RN with median time to RN after initial SRS treatment of 26.5 mo (range 2.0-220.5 mo). Of patients with RN, 8 (34.8%) received antibody-drug conjugates (ADC) concurrently with SRS. Conclusions: TUC and T-DXd are increasingly prescribed as initial systemic treatment after BM diagnosis. The combination of SRS and HER2 targeted therapies in this cohort resulted in excellent survival outcomes with limited risk of RN. Future studies and longer follow-up will allow for a better understanding of how treatment patterns affect survival outcomes and patient quality of life.