title: Melanoma brain metastases and vemurafenib: need for further investigation.
abstract: Brain metastases are a major cause of morbidity and mortality in patients with advanced melanoma. With the development of targeted agents for the treatment of metastatic melanoma, a great deal of interest has focused on whether selective BRAF inhibitors may play a role in the treatment of brain metastases in lieu of or in addition to surgery and/or radiation therapy. However, relatively little is known about the intracranial effectiveness of vemurafenib, the only US Food and Drug Administration-approved selective BRAF V600E inhibitor, because patients with brain metastases have historically been excluded from vemurafenib clinical trials. We describe 3 patients with BRAF V600E mutation metastatic melanoma in whom treatment with vemurafenib resulted in prompt extracranial disease response but progression of metastatic disease in the brain. Further, we discuss possible mechanisms responsible for the suboptimal central nervous system response observed in these patients and alternative therapies for patients with melanoma metastatic to the brain.
authors.affiliation: Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Rochet
authors.forename: Roxana S
authors.initials: RS
authors.lastname: Dronca
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Kottschade
authors.forename: Rahul N
authors.initials: RN
authors.lastname: Chavan
authors.forename: Brian
authors.initials: B
authors.lastname: Gorman
authors.forename: Julie R
authors.initials: JR
authors.lastname: Gilbertson
authors.forename: Svetomir N
authors.initials: SN
authors.lastname: Markovic
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D018450:Disease Progression; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary*; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013449:Sulfonamides / Q000627:therapeutic use*; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf