Successful Treatment of a Progressive BRAF V600E-Mutated Anaplastic Pleomorphic Xanthoastrocytoma With Vemurafenib Monotherapy.

Introduction Pleomorphic xanthoastrocytoma (PXA) is a rare brain tumor that most commonly affects children and young adults. PXA undergoes anaplastic transformation in 15% to 20% of patients. Although the prognosis is relatively favorable for patients with a WHO grade 2 PXA, data suggest that the prognosis for anaplastic PXA is significantly worse. Maximal resection is generally recommended, but the role of radiation or chemotherapy in the management of these tumors remains unclear. Alterations in the BRAF gene have been described in several pediatric low-grade gliomas. Approximately 70% of pilocytic astrocytomas contain BRAF fusions, resulting from a tandem duplication and rearrangement on 7q34 between BRAF and a gene centromeric to BRAF. This is in contrast with PXA, in which the described BRAF alteration is instead a BRAF mutation that results from an amino acid substitution replacing valine (V) with glutamic acid (E) at position 600. This BRAF V600E mutation is found in approximately 60% to 65% of WHO grade 2 and 3 PXAs, and is the same mutation that is found in approximately 50% of melanomas. Vemurafenib is a BRAF inhibitor that is approved for the treatment of BRAF-mutated metastatic melanoma in the United States and the European Union. There are several case reports of CNS melanoma metastases that were responsive to vemurafenib, and preliminary results from an open-label pilot study of vemurafenib for patients with melanoma and brain metastases suggest some activity. This evidence indicates that vemurafenib may penetrate CNS tumors. In addition, BRAF inhibition represses the growth of intracranial BRAF V600E pediatric malignant astrocytoma xenografts in mouse models. Hence, vemurafenib may have a role in the treatment of intracranial neoplasms with BRAF mutations. In support of this, we now present a case of a progressive BRAF V600E–mutated anaplastic PXA that was successfully treated with vemurafenib monotherapy.