BIOM-93. PROGNOSTIC AND PREDICTIVE IMPLICATIONS OF BRAF V600 MUTATIONS IN ADULT HIGH-GRADE GLIOMAS

Abstract BRAF V600 mutations (BRAF-V600m) drive constitutive activation of the MAPK pathway, leading to uncontrolled proliferation and survival. Basket trials led to tissue-agnostic approval of dabrafenib/trametinib for recurrent BRAF-V600E mutant solid tumors, including gliomas. However, the prognostic and predictive significance of these mutations in adult high-grade gliomas (HGG) remains unclear. Our prior limited single-institution data suggested a potential survival benefit with MAPK inhibitors (MAPKi), though without statistical significance. Here, we evaluate the prognostic and predictive impact of BRAF-V600m in a larger cohort. Retrospective, de-identified data were obtained from the Caris Life Sciences’ clinic-genomic (CODEai) platform. Next-generation sequencing was performed using Caris Life Sciences’ assay. Kaplan-Meier and log-rank tests were used for survival analysis. A p<0.05 was determined as significant. Among 12,708 patients with HGGs, 200 (1.6%) had tumors harboring BRAF-V600m, of whom 139 (69%) were MAPKi-naïve. BRAF-V600m was not prognostic in this population (median overall survival (OS) 16.9 months BRAF-V600m vs. 16.7 months BRAF wild-type; HR=1.05, 95% CI: 0.85–1.30; p=0.605). Similar results were observed among 8,974 patients with glioblastoma (GBM), n=112 BRAF-V600m(1.3%), n=80 (71%) MAPKi-naïve, (median OS 14.9 vs. 12.5 months; HR=0.90, 95% CI: 0.70–1.16; p=0.442). However, treatment with MAPKi significantly improved OS in both cohorts (HGG: 24.8 vs. 16.7 months; HR=0.56, 95% CI:0.37-0.85; p=0.006; GBM: 23.1 vs. 12.5 months; HR=0.50, 95% CI:0.31-0.83; p=0.006). Additional data on progression-free survival (PFS) following upfront standard-of-care radiotherapy and temozolomide for all subgroups will be presented. BRAF-V600m is not a prognostic biomarker in HGG or GBM, but it is predictive of benefit from treatment with MAPK inhibitors at recurrence.