Lgg-23. outcomes utilizing braf inhibition monotherapy in brafv600e mutated pediatric low grade gliomas

Abstract 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 BRAFV600E 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 BRAFV600E 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 BRAFV600E 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 BRAFV600E 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