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Upfront BRAF/MEK inhibitors for treatment of high-grade glioma: A case report and review of the literature

Gabrielle Arbour, Benjamin Ellezam, Alexander G. Weil, Romain Cayrol, Magimairajan Vanan, Hallie Coltin, Valérie Larouche, Craig Erker, Nada Jabado, Sébastien Perreault

2022Neuro-Oncology Advances14 citationsDOIOpen Access PDF

Abstract

Abstract Background High-grade gliomas (HGG) with BRAFV600E mutation represent a unique subset of central nervous system tumors. Targeted therapies including BRAF and MEK inhibitors are now being explored as possible new treatment options. Methods We report an 18-year-old female with a grade 3 pleomorphic xanthoastrocytoma treated upfront with dabrafenib and trametinib. We also conducted a systematic literature review of patients with HGG and BRAFV600E mutations treated with BRAF inhibitors. Results Despite local recurrences resected surgically, the patient has been on dabrafenib and trametinib for more than 54 months. Thirty-two patients with HGG and BRAFV600E mutations treated with BRAF inhibitors were retrieved through our systematic review of the literature. Only 1 young patient with an anaplastic ganglioglioma was treated upfront with a BRAF inhibitor with a curative intent. Best response reported with radiation therapy and systemic therapy was a stable disease (SD) for 18 patients (56.3%) and progressive disease (PD) for 9 patients (28.1%). Responses to treatment regimens that included BRAF inhibitors were reported in 31 patients and included 4 complete responses (12.9%), 23 partial responses (74.2%), 2 SDs (6.5%), and 2 PDs (6.5%). Conclusions Our patient had durable disease control with dabrafenib and trametinib. Given favorable responses reported in patients with HGG treated with BRAF inhibitors, we believe that upfront targeted therapy is a possible treatment approach that should be studied in the context of a clinical trial.

Topics & Concepts

DabrafenibTrametinibMedicinePleomorphic xanthoastrocytomaOncologyContext (archaeology)Internal medicineMEK inhibitorGliomaClinical trialTargeted therapyVemurafenibCancer researchCancerMAPK/ERK pathwayAstrocytomaMetastatic melanomaBiologyKinasePaleontologyCell biologyGlioma Diagnosis and TreatmentMelanoma and MAPK PathwaysBrain Metastases and Treatment