LGG-23. OUTCOMES UTILIZING BRAF INHIBITION MONOTHERAPY IN BRAF(V600E) MUTATED PEDIATRIC LOW GRADE GLIOMAS

BACKGROUND: Pediatric low-grade glioma (pLGG) tumorigenesis is driven by activation of the RAS/RAF/MAPK pathway. pLGGs have an overall survival over 95%; however, patients harboring a BRAF(V600E) alteration may have worse outcomes. Combined BRAF/MEK inhibition following incomplete resection demonstrated improved outcome in pLGG compared to combined carboplatin/vincristine chemotherapy. We evaluated efficacy and tolerability of single agent BRAF inhibitor treatment in our single institution pLGG cohort. METHODS: We performed a single institution retrospective analysis, (2013-2023) at Children’s Healthcare of Atlanta on patients 0-21 years old with new or progressive BRAF(V600E) mutated pLGG, who were treated off-study with BRAF inhibitor monotherapy. We evaluated 2-year Progression Free Survival (PFS) and Objective Response (CR+PR). All toxicities were evaluated and described. RESULTS: We identified fifteen patients with BRAF(V600E) mutated pLGGs treated with BRAF inhibitor monotherapy. Median age of diagnosis: 5.8 years (0.20–18.0). Histologic diagnosis: pilocytic astrocytoma (PA)(N=3); atypical PA (N=1); ganglioglioma (N=3); atypical ganglioglioma (N=3); pleomorphic xanthoastrocytoma (PXA)(N=2); LG neuroepithelial tumor (N=1); infiltrating glioma (N=1); and LGG (NOS)(N=1). Tumor location: hypothalamus/optic chiasm (N=5); third ventricle/thalamus (N=3); parietal/temporal lobe (N=3); brainstem (N=2); and cervicomedullary junction/spinal cord (N=2). Mean therapy duration: 30.7 months (3.9-74.6). Median follow-up: 32.6 months (16-78.1). Two-year PFS: 80% (12/15). Objective Response(OR) for 14 evaluable patients at 1-year on initial BRAF inhibitor therapy: 43% (0/14 CR+6/14 PR). Patients tolerated treatment with Grade 1 rash being the most common toxicity. Three of 15 patients (20%) discontinued therapy due to toxicities, including rashes, arthralgias/myalgias (Grade 2), and one corneal lesion. CONCLUSIONS: In our small cohort of incompletely resected BRAF(V600E) mutated pLGGs, BRAF inhibition monotherapy was effective and well tolerated with an OR comparable to published outcomes of dual MEK/BRAF inhibitor therapy. This promising treatment should be further studied in prospective clinical