Response to combined BRAF/MEK inhibition in adult BRAF V600E mutant spinal pilocytic astrocytoma

Highlights

• We describe the first reported case of an adult patient with a spinal pilocytic astrocytoma and BRAF V600E mutation.

• We report the successful use of targeted therapy against the BRAF and MAP Kinase pathways.

• Our patient achieved a radiological response predominantly with MEK inhibitor monotherapy.

Abstract

Pilocytic astrocytomas are World Health Organisation (WHO) grade I tumors, occurring predominantly supratentorially and in the pediatric population. Although the mainstay of treatment is local therapies such as surgery, targeted systemic therapies may be necessary for recurrent or unresectable disease. The majority of sporadic pilocytic astrocytomas are associated with the BRAF-KIAA fusion gene, which results in constitutive activation of the MAP Kinase pathway. Less frequently, the BRAF V600E point mutation has been described, occurring in less than 10% of supratentorial pilocytic astrocytomas. Tumours with this mutation may respond to targeted therapy against the BRAF/MAP Kinase pathway. We report the first described case of a spinal pilocytic astrocytoma in an adult patient with a BRAF V600E mutation responding to targeted therapy using BRAF and MEK tyrosine kinase inhibitors, and share our experiences with the management of toxicity in this patient population.

Introduction

Pilocytic astrocytomas (PAs) are relatively indolent tumours predominantly diagnosed in the paediatric population. Local therapies such as surgery and radiotherapy are traditional mainstays of treatment. These tumors can progress despite such measures requiring systemic therapy for disease control, with increasing interest in druggable molecular aberrations. Adult PAs are particularly rare, displaying a more aggressive phenotype with worse outcomes [1].

60–80% of sporadic PAs are associated with the BRAF-KIAA fusion gene that results in constitutive activation of the MAP Kinase pathway [2]. The BRAF V600E point mutation, which is mutually exclusive with BRAF fusions, is very rarely seen in non-pediatric Pas [1]. Despite portending a worse prognosis historically, they may be amenable to targeted therapy [3].

We describe a rare case of spinal pilocytic astrocytoma (SPA) in an adult patient with a BRAF V600E mutation, and outline our experience using targeted therapy for this patient with BRAF and MEK tyrosine kinase inhibitors (TKI).