Response to Dabrafenib and Tramatenib in an Extra-Cranial Avm with BRAF V600E Mutation

Abstract

Background: Arteriovenous malformations (AVMs) are blood vessel malformations characterized by shunting of blood through dilated veins and arteries. KRAS is an effector molecule in a MAPK pathway that mediates activation of downstream processes such as BRAF production related to known proliferative disorders such as AVMs. Similarly MAP2K1 mutations that encodes for MEK have recently been implicated in sporadic intracranial and extracranial AVMs. Inhibition of the RAS/MAPK pathway is of interest in treatment of vascular malformations. Objective: We report a case of treatment response of a BRAF mutated arteriovenous malformation with MEK and RAF inhibitors. Description of the case: A 22 year old male presented initially at 6 years of age with swelling of the left face involving the cheek and mandible area, the area continued to grow in size with associated pain and rarely intermittent bleeding from the left buccal mucosa. US and MRI showed evidence of an AVM. He underwent 2 embolizations followed by debulking with some improvement of the swelling. Pathology revealed a BRAF V600 mutation by molecular testing. He was treated with oral Dafrafenib 150 mg twice daily and Trametinib 2 mg daily, showing improvement of the swelling with a 3 month old follow up. Conclusion: AVMs continue to present treatment challenges for hematologists, surgeons and other care providers. Treatment with target directed therapies with inhibitors of the RAS-RAF-MEK-ERK pathway such as Trametinib and Dafrafenib have the potential to make a positive impact in the current management of these entities. Further studies are required to explore safety and impact of long term effects of these drugs in pediatric patients.