BRAF/MEK double blockade in refractory anaplastic pleomorphic xanthoastrocytoma
Denis Migliorini, MD,
Diego Aguiar, MD, Maria-Isabel Vargas, MD, Alexander Lobrinus, MD, and Pierre-Yves Dietrich, MD
Diego Aguiar, MD, Maria-Isabel Vargas, MD, Alexander Lobrinus, MD, and Pierre-Yves Dietrich, MD
A 32-year-old woman was diagnosed in February 2012 with a grade II pleomorphic xanthoastrocytoma (PXA) of the right parietal lobe. A complete excision was performed, followed by tumor bed irradiation (66 Gy). A local relapse occurred in September 2013, for which a partial resection was performed, confirming a grade II PXA. Immunohistochemical analysis indicated the presence of a BRAFV600E mutated protein, and combined treatment with vemurafenib and bevacizumab was initiated. A partial response was rapidly obtained, sustained for 12 months. In June 2015, a third surgery was performed for an extended relapse invading the right cerebral hemisphere. Histopathologic examination revealed anaplastic (grade III) PXA and confirmed the presence of the BRAFV600E mutation (figure, A and B). After unsuccessful treatment with bevacizumab and lomustine, tumor treating fields therapy was applied between August and December 2015. Treatment was complicated by severe skin toxicity, with progressive appearance of a 4-cm scalp wound. Concurrently, the patient developed a severe left hemiparesis with ataxia, hemispatial neglect, and central facial palsy. MRI revealed major disease progression. The patient was subsequently referred to our institution.
Pathologic characterization of anaplastic pleomorphic xanthoastrocytoma (PXA) and radiologic response to BRAF/MEK double blockade therapy
We initiated combination therapy with dabrafenib 300 mg/d (BRAF inhibitor) and trametinib 2 mg/d (MEK inhibitor) in January 2016. Tolerance was poor, with noninfectious fever, grade III neutropenia, and vomiting. Following reduction of the dabrafenib dose to 150 mg/d, all side effects gradually resolved within 3 weeks. An impressive clinical and radiologic response was observed, with improvement in general condition and regaining of autonomy, partial recovery of the motor deficit, and disappearance of headaches. The response and clinical benefit is ongoing at 11 months of treatment. The figure, C, illustrates the major radiologic changes during this treatment.
