title: Salvage therapy with BRAF inhibitors for recurrent pleomorphic xanthoastrocytoma: a retrospective case series.
abstract: 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.
authors.affiliation: Department of Neurology and Neurological Surgery, University of Washington, Seattle, WA 98109, USA. chambemc@u.washington.edu
authors.forename: Marc C
authors.initials: MC
authors.lastname: Chamberlain
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001254:Astrocytoma / Q000235:genetics / Q000628:therapy*; D001932:Brain Neoplasms / Q000235:genetics / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D013449:Sulfonamides / Q000627:therapeutic use*; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf