MMAP-07 CNS METASTATIC PATTERNS IN BREAST CANCER TREATED WITH ALPELISIB: PRELIMINARY RESULTS OF A RETROSPECTIVE ANALYSIS

Abstract BACKGROUND Alpelisib is FDA-approved for patients with HR-positive, HER-2 negative, PIK3CA-mutated metastatic breast cancer with progression on/after receiving endocrine therapy. We investigated the CNS progression patterns of patients on alpelisib. METHODS We queried the Johns Hopkins Electronic Medical records from 5/2019-4/2024 using the following criteria: 1) Age ≥18 years; 2) Diagnosis and/or problem list including breast cancer; 3) ≥2 months of documented alpelisib therapy. Patients were subsequently dichotomized based on the ICD10 codes for CNS metastases. RESULTS Forty-three female patients were identified (74% White, 19% Black, 7% Asian, 2% Hispanic). Median age was 60 years (range 35-87). Alpelisib was the median third line therapy (total lines 2-13). Median time on alpelisib was 7.1 months (2.2-23.9 [IQR 3.6-10.3]). Six patients (14%) had preexisting CNS disease before alpelisib, and 37 (86%) had no previous CNS involvement. The non-CNS involvement patients were on drug for 7.9 months on average (range 2.2-23.9 [IQR 3.6-10.3]), whereas those with preexisting CNS disease were on drug 4.7 months (range 2.8-11.0 months). While on alpelisib, six patients (16%) developed new CNS disease (mean time of 6.1 months [range 3.5-9.5]). In the preexisting CNS disease group, only one patient had confirmed CNS progression in the leptomeninges after 3.8 months. A total of 7 (16%) patients suffered CNS progression; 4 involved dural/leptomeningeal, and 2 brain/spinal parenchymal and 1 progression in both. Overall survival from initiation was 12.2±11.2 months in the pre-alpelisib brain metastases group versus 18.9±12.3 months (log-rank p=0.03) in the non-CNS group. Two (16%) known causes of death were neurologic; both developed metastases while on alpelisib (5.8 and 9.0 months after initiation). CONCLUSION This is a work-in-progress of CNS metastatic patterns in patients who received alpelisib, showing a leptomeningeal predominance in CNS progression. A detailed radiographic review of the metastasis cases is pending.