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J Neurosurg. 2019 Nov 1:1-6. doi: 10.3171/2019.8.JNS19643. [Epub ahead of print]

Dual BRAF/MEK therapy in BRAF V600E-mutated primary brain tumors: a case series showing dramatic clinical and radiographic responses and a reduction in cutaneous toxicity.

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1Department of Public Health and Primary Care, University of Cambridge, United Kingdom.
2Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
Departments of3Neurosurgery.
4Dermatology, and.
5Departments of Pathology and Medicine, Division of Dermatology, The Ohio State University Wexner Medical Center, Columbus, Ohio.
6Oncology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; and.



BRAF V600E is a common oncogenic driver in a variety of primary brain tumors. Dual inhibitor therapy using dabrafenib (a selective oral inhibitor of several mutated forms of BRAF kinase) and trametinib (a reversible inhibitor of MEK1 and MEK2) has been used successfully for treatment of metastatic melanoma, anaplastic thyroid cancer, and other tumor types, but has been reported in only a few patients with primary brain tumors and none with pleomorphic xanthoastrocytoma. Here, the authors report on the substantial clinical response and reduction in cutaneous toxicity in a case series of BRAF V600E primary brain cancers treated with dual BRAF/MEK inhibitor therapy.


The authors treated 4 BRAF V600E patients, each with a different type of primary brain tumor (pilocytic astrocytoma, papillary craniopharyngioma, ganglioglioma, and pleomorphic xanthoastrocytoma) with the combination of dabrafenib and trametinib.


The patients with pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and papillary craniopharyngioma experienced near-complete radiographic and complete clinical responses after 8 weeks of therapy. A substantial partial response (by RANO [Response Assessment in Neuro-Oncology] criteria) was observed in the patient with ganglioglioma. The patient with craniopharyngioma developed dramatic, diffuse verrucal keratosis within 2 weeks of starting dabrafenib. This completely resolved within 2 weeks of adding trametinib.


Dual BRAF/MEK inhibitor therapy represents an exciting treatment option for patients with BRAF V600E primary brain tumors. In addition to greater efficacy than single-agent dabrafenib, this combination has the potential to mitigate cutaneous toxicity, one of the most common and concerning BRAF inhibitor-related adverse events.


BRAF mutation; RANO = Response Assessment in Neuro-Oncology; chemotherapy; oncology; primary brain tumor


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