title: Vemurafenib in patients with BRAF(V600) mutation-positive melanoma with symptomatic brain metastases: final results of an open-label pilot study.
abstract: OBJECTIVE
  Brain metastases are frequent in patients with metastatic melanoma, indicating poor prognosis. We investigated the BRAF kinase inhibitor vemurafenib in patients with advanced melanoma with symptomatic brain metastases.
  
  
  METHODS
  This open-label trial assessed vemurafenib (960mg twice a day) in patients with BRAF(V600) mutation-positive metastatic melanoma with non-resectable, previously treated brain metastases. The primary end-point was safety. Secondary end-points included best overall response rate, and progression-free and overall survival.
  
  
  RESULTS
  Twenty-four patients received vemurafenib for a median treatment duration of 3.8 (0.1-11.3) months. The majority of discontinuations were due to disease progression (n=22). Twenty-three of 24 patients reported at least one adverse event (AE). Grade 3 AEs were reported in four (17%; 95% confidence interval [CI], 4.7-37.4%) patients and included cutaneous squamous cell carcinoma in four patients. Median progression-free survival was 3.9 (95% CI, 3.0-5.5) months, and median survival was 5.3 (95% CI, 3.9-6.6) months. An overall partial response (PR) at both intracranial and extracranial sites was achieved in 10 of 24 (42%; 95% CI, 22.1-63.4) evaluable patients, with stable disease in nine (38%; 95% CI, 18.8-59.4) patients. Of 19 patients with measurable intracranial disease, seven (37%) achieved >30% intracranial tumour regression, and three (16%; 95% CI, 3.4-39.6%) achieved a confirmed PR. Other signs of improvement included reduced need for corticosteroids and enhanced performance status.
  
  
  CONCLUSIONS
  Vemurafenib can be safely used in patients with advanced symptomatic melanoma that has metastasised to the brain and can result in meaningful tumour regression.
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. Electronic address: reinhard.dummer@usz.ch.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Simone M
authors.initials: SM
authors.lastname: Goldinger
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Turtschi
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Nina B
authors.initials: NB
authors.lastname: Eggmann
authors.affiliation: Multidisciplinary Center Lausanne, Quartier UNIL-Sorge, Lausanne, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Michielin
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Lada
authors.initials: L
authors.lastname: Mitchell
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Luisa
authors.initials: L
authors.lastname: Veronese
authors.affiliation: MRI Bethanien, Zurich, Switzerland.
authors.forename: Paul René
authors.initials: PR
authors.lastname: Hilfiker
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Lea
authors.initials: L
authors.lastname: Felderer
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Jeannine D
authors.initials: JD
authors.lastname: Rinderknecht
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000556:secondary*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D010865:Pilot Projects; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D000077484:Vemurafenib; D055815:Young Adult
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: Advanced melanoma; BRAF inhibitor; BRAF mutation; Safety; Symptomatic brain metastases; Tumour regression; Vemurafenib