SDPS-10 DISPARITIES IN THE RISK OF CNS METASTASIS AND CLINICAL OUTCOMES IN PATIENTS WITH HER2- MUTATION POSITIVE (HER2+) NON-BREAST VERSUS HER2+ BREAST CANCERS

BACKGROUND: Risk of CNS metastases is well characterized for patients (pts) with HER2+ breast cancer (BC), however, poorly defined for pts with HER2+ non-breast solid tumors (ST). METHODS: We performed a retrospective cohort analysis to characterize the frequency of CNS metastasis and clinical outcomes in pts with Her2+ ST treated at the University of Virginia Emily Couric Cancer Center between 01/2010- 01/2022. Risk of CNS metastasis, time to CNS metastasis, progression free survival (PFS) and overall survival (OS) were analyzed for each cohort and stage IV subgroups. The outcomes were further compared between HER2+ ST vs BC cohorts. RESULTS: 50 pts had HER2+ ST and 383 had HER2+ BC. In the ST group, median age was 66.0 years (y), 37 (74.0%) were male, 43 (86.0%) were white and 2(4.0%) were African American. Majority (74%) of patients had gastro-esophageal tumors. Median time to CNS metastasis was 5.8 y and median PFS was 0.7 y (95% CI 0.55-0.98, p<0.05). In those with CNS metastasis 5 (50%) received CNS directed plus HER2 targeted therapy and 3(30%) received CNS directed therapy alone. 24 (48%) pts had baseline CNS imaging in ST group, compared to 11 (2.9%) in the BC group. Rate of CNS metastasis was 20% (n=10) vs 6.8% (n=26) in the ST and BC cohorts (p<0.0001). OS differs in ST vs BC cohorts overall (p<0.0001; median OS 1.7 vs 18.5y) and in patients with metastatic disease at diagnosis (p<0.0001; median OS 1 vs 6.3y). Advanced N (p=0.0445) and smoking (p=0.0868) were associated with early CNS metastasis CONCLUSIONS: Pts with HER2+ ST have higher risk of CNS metastasis and shorter OS compared to BC pts. Improved understanding of disease characteristics and standardized management approaches are imminently needed to improve outcomes.