INNV-25. Efficacy of dabrafenib plus trametinib in <i>BRAF</i> -mutant gliomas: a retrospective series

Abstract BACKGROUND Consistent data support the efficacy of BRAF and MEK inhibitors in paediatric patients with low-grade gliomas, while data in adults are more limited, and the clinical benefit is to be defined. PATIENTS AND METHODS We retrospectively collected data of adult patients with BRAF-mutant gliomas treated between 2004 and 2024 in our Institution. Twelve patients received dabrafenib plus trametinib at recurrence after standard radiotherapy and chemotherapy. Histo-molecular diagnoses were reviewed according to WHO 2021. Radiological response was re-evaluated according to RANO criteria. RESULTS We identified 12 patients (5 males and 7 females), with age ranging from 21 to 53 years. At baseline, all patients had contrast-enhancing tumours and were neurologically symptomatic. Three out of 12 patients (25%) displayed a complete response: 1 pilocytic astrocytoma (PA), 1 anaplastic pleomorphic xanthoastrocytoma (PXA), and 1 glioblastoma (GBM). Two patients achieved either seizure reduction &amp;gt;50% or seizure freedom. A F-DOPA PET confirmed a metabolic response in the GBM patient. Four out of 12 patients (33%) displayed a partial response (2 PA, 1 ganglioglioma - GG, 1 GBM), together with neurological improvement. Two (1 PXA, 1 GBM) out of 12 patients (17%) displayed a stable disease, with seizure freedom in 1. Three patients (25%) (1 PXA, 2 GBM) displayed an early tumour progression. PFS ranged from 7 to 24 months and OS from 8 to 46 months. Five patients are still on treatment. Adverse effects included headache (7/12) fever (4/12) and cutaneous reactions (3/12), leading to dose reduction in 2 patients. CONCLUSIONS This cohort of recurrent and/or disseminated BRAF-mutant gliomas displayed a high response rate on MRI following dabrafenib plus trametinib (CR+PR 58%), with improvement of seizures (3/8, 37%). More data are needed to assess the long-term duration of response, and to investigate molecular factors influencing the probability of response.