Clinical and radiological response to combined BRAF and MEK inhibitors therapy in a case of recurrent, progressive pleomorphic xanthoastrocytoma (PXA).

Background: BRAF gene mutations are well documented in a subset of gliomas, including pleomorphic xanthoastrocytoma (PXA), ganglioglioma, pilocytic astrocytoma, and epithelioid glioblastoma. PXA is rare, accounting for less than 1% of all astrocytic tumors, and two-thirds harbor a specific BRAF point mutation at V600E. Although the development of targeted BRAF inhibitors has dramatically improved the clinical outcomes for patients with BRAF V600E mutant tumors, such as melanoma, resistance develops in the majority of cases. Additional treatment with a MEK inhibitor could improve tumor control and survival. Application of dual inhibitors in PXA is rarely reported. Case Information: We report a case of 29-year-old woman with recurrent PXA with BRAF V600E mutation whose tumor was resistant to standard and salvage treatments including resections, thermal ablation, chemotherapy, and radiation, with partial response for 68 months. With disease progression while on temozolomide, a targeted treatment with combined BRAF inhibitor vemurafenib (Zelboraf) and MEK inhibitor cobimetinib (Cotellic) were initiated. The patient demonstrated significant clinical and radiological response with no disease progression for 10 months at time of this presentation. She continues therapy with the combined inhibitor therapy, with minimal side effects. Conclusions: PXA poses a therapeutic challenge due to its rarity, lack of consensus guidelines for treatment at recurrence, and no effective chemotherapeutic drugs. This case report describing significant response is encouraging. It adds to a small number of published reports highlighting the utility of BRAF and MEK combined inhibitor therapy in refractory PXA.