CNSC-62. DIFFERENTIAL SURVIVAL IMPACT OF TRASTUZUMAB DERUXTECAN IN HER2-POSITIVE VERSUS HER2-LOW BREAST CANCER PATIENTS WITH BRAIN METASTASES

Abstract BACKGROUND Brain metastases (BM) in breast cancer (BC) present significant treatment challenges, with varying outcomes based on HER2 expression. There is limited real-world evidence of outcomes with the use of trastuzumab deruxtecan (T-DXd) on survival in patients (pts) with HER2-low and HER2-positive (HER2+) MBC with BM. METHODS We conducted a retrospective cohort study using data from seven US-based health systems within the Guardian Research Network (GRN). We included pts treated with T-DXd from December 2019 to December 2023, classified as HER2-low (IHC 1+ or IHC 2+/HER2 FISH non-amplified) or HER2+ (IHC 3+ or HER2+ with FISH amplified). Survival analysis was performed using Kaplan-Meier curves and the log-rank test. RESULTS 125 pts with BCBM treated with T-DXd were included in the final analysis, of which 70 (56%) were HER2+ and 55 (44%) were HER2-low. The median age at BM diagnosis was 60.5 years (range 21.6 to 87.1 years). HER2 low pts had a higher prevalence of ER+ disease than HER2+ pts (81.9% vs. 55.7%, p=0.01). Most of these pts (≥75%) had received multiple prior lines of therapy. HER2+ pts with BM had a median overall survival (mOS) of 9.3 months (95% CI: 6.79-11.88), significantly longer than 4.3 months (95% CI: 1.89-6.82) in HER2-low pts (p < 0.001). At 6 months, OS for HER2+ pts with BM was 40% compared to 25% in HER2-low pts. At 12 months, OS for HER2+ pts was 20% compared to 10% in HER2-low pts. CONCLUSIONS This study represents the largest real-world evidence to date on the effectiveness of T-DXd in treating BM from breast cancer. HER2+ BCBM exhibited longer mOS and 12-month survival rates than pts with HER2-low disease, suggesting HER2 expression is crucial in determining T-DXd’s effectiveness. Future research should explore combination therapies and identify predictive biomarkers to optimize treatment strategies through clinical trials.