Salvage therapy with BRAF inhibitors for recurrent pleomorphic xanthoastrocytoma: a retrospective case series.

Pleomorphic xanthoastrocytoma (PXA) is a World Health Organization Grade 2 glioma that is uncommon (<1 % all adult gliomas) and seen primarily in children and young adults. PXA has been demonstrated to manifest the V600E BRAF mutation in nearly 70 % of all tumors, a mutation that constitutively activates the BRAF/MEK signaling pathway. Assess response and toxicity of a BRAF inhibitor, vemurafenib, in recurrent PXA manifesting the V600E mutation. Four adults [2 males; 2 female: median age 45 years (range 34-53)] with surgery, radiation and alkylator refractory recurrent PXA demonstrating the BRAF mutation (V600E) were treated with vemurafenib. A cycle of vemurafenib was defined as 4 weeks of continuous therapy. All toxicities seen were grade 2 and included arthralgia, photosensitivity, fatigue and nausea (1 patient each). The median number of cycles of therapy was 5 (range 2-10). Radiographic response was progressive disease in 1, stable disease in 2 and partial response in 1. Median progression free survival was 5 months (range 2-10 months). Median overall survival was 8 months (range 4-14 months). In this small retrospective series of select patients with recurrent PXA manifesting the BRAF V600E activating mutation, vemurafenib appears to have single agent activity with manageable toxicity. Confirmation in a larger series of similar patients is required.