To describe intracranial and leptomeningeal response of BRAFV600E-mutant (mt) gliomas to combination encorafenib/binimetinib.

Glioblastomas carry a dismal prognosis. After first-line therapy, progression is inevitable with subsequent progression-free survival less than 6 months. A subset of adult gliomas harbor oncogenic mutations in BRAF. Response to BRAF and/or MEK inhibition with early generation agents has been described and correlated with mutation clonality. Newer agents encorafenib and binimetinib are effective in melanoma brain metastases. Response in gliomas has not been described.

We offer a retrospective report of two patients with BRAFV600E-mt glioma treated with off-label combination encorafenib/binimetinib.

Patient 1: A 25-year-old man with a subtotally resected BRAF-mt astrocytoma with pilocytic features experienced tumor growth after 18 months. Re-resection pathology confirmed high-grade BRAFV600E-mt glioma with variant allelic frequency (VAF) of 46.8%. He underwent radiation therapy (RT) and temozolomide (TMZ). Immediately following RT he developed hydrocephalus requiring ventriculoperitoneal shunting. MRI spine revealed diffuse enhancement and lumbar puncture confirmed presence of malignant cells. He was subsequently started on encorafenib/binimetinib. Follow up MRI demonstrated residual tumor stability with near complete resolution of leptomeningeal disease. He remains progression free after 6 months. Patient 2: A 75-year-old man with vision loss and memory impairment was diagnosed with an enhancing intracranial mass. Pathology suggested high-grade glioma with ependymal differentiation. Targeted exon sequencing confirmed the diagnosis of BRAFV600E-mt glioblastoma with VAF of 36%. He underwent RT/TMZ but ultimately progressed radiographically after 5 cycles of adjuvant TMZ. He was started on encorafenib/binimetinib resulting in decreased enhancement and clinical stability for 18 months, complicated only by renal insufficiency. Both patients are tolerating encorafenib/binimetinib well. 

Based on these two retrospective case reports, encorafenib/binimetinib appear to confer favorable and lasting efficacy for BRAFV600E-mt glioma in both the parenchyma and leptomeninges. To our knowledge, this is the first report of glioma response to these specific agents.