title: Treatment patterns and outcomes in BRAF V600E-mutant melanoma patients with brain metastases receiving vemurafenib in the real-world setting.
abstract: Brain metastases are a common and serious complication among patients with metastatic melanoma. The selective BRAF inhibitor vemurafenib has demonstrated clinical efficacy in patients with BRAF V600E-mutant melanoma brain metastases (MBM). We examined the real-world application and clinical outcomes of vemurafenib in this patient population. Demographic, treatment patterns, response, and survival data were collected from medical charts. Clinical data on 283 patients with active BRAF V600E-mutant MBM treated with vemurafenib were provided by 70 US oncologists. Mean age was 57.2 years, 60.8% were male, 67.5% had ECOG performance status of 0-1, and 43.1% used corticosteroids at vemurafenib initiation. Median follow-up was 5.7 months. Following vemurafenib initiation, 48.1% of patients experienced intracranial response and 45.6% experienced extracranial response. The Kaplan-Meier estimate for overall survival was 59% at 12 months. Multivariate analyses showed associations between intracranial response and both corticosteroid use and vemurafenib as initial therapy after MBM diagnosis. Larger size (5-10 mm vs. < 5 mm) and number of brain metastases (≥ 5 vs. < 2) and progressive extracranial disease at treatment initiation were associated with decreased intracranial response and increased risk of disease progression. Multiple extracranial sites (2 vs. < 2) and the absence of local treatments were also associated with increased risk of progression. Increased risk of death was associated with ≥ 2 extracranial disease sites, progressive extracranial disease, and ≥ 5 brain metastases. Subgroups of MBM patients may derive more benefit with vemurafenib, warranting prospective investigation.
authors.affiliation: Moffitt Cancer Center, Tampa, Florida.
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Gibney
authors.affiliation: Analysis Group Inc., Boston, Massachusetts.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Gauthier
authors.affiliation: Analysis Group Inc., Boston, Massachusetts.
authors.forename: Charles
authors.initials: C
authors.lastname: Ayas
authors.affiliation: Analysis Group Inc., Boston, Massachusetts.
authors.forename: Philip
authors.initials: P
authors.lastname: Galebach
authors.affiliation: Analysis Group Inc., Boston, Massachusetts.
authors.forename: Eric Q
authors.initials: EQ
authors.lastname: Wu
authors.affiliation: Genentech Inc., South San Francisco, California.
authors.forename: Sarang
authors.initials: S
authors.lastname: Abhyankar
authors.affiliation: Genentech Inc., South San Francisco, California.
authors.forename: Carolina
authors.initials: C
authors.lastname: Reyes
authors.affiliation: Analysis Group Inc., Boston, Massachusetts.
authors.forename: Annie
authors.initials: A
authors.lastname: Guérin
authors.affiliation: Genentech Inc., South San Francisco, California.
authors.forename: Yeun Mi
authors.initials: YM
authors.lastname: Yim
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF mutation; brain metastases; melanoma brain metastases; metastatic melanoma; vemurafenib