title: Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib.
abstract: BACKGROUND
  Approximately 50% of melanomas harbor activating (V600) mutations in the serine-threonine protein kinase B-RAF (BRAF). The oral BRAF inhibitor vemurafenib (PLX4032) frequently produced tumor regressions in patients with BRAF V600-mutant metastatic melanoma in a phase 1 trial and improved overall survival in a phase 3 trial.
  
  
  METHODS
  We designed a multicenter phase 2 trial of vemurafenib in patients with previously treated BRAF V600-mutant metastatic melanoma to investigate the efficacy of vemurafenib with respect to overall response rate (percentage of treated patients with a tumor response), duration of response, and overall survival. The primary end point was the overall response rate as ascertained by the independent review committee; overall survival was a secondary end point.
  
  
  RESULTS
  A total of 132 patients had a median follow-up of 12.9 months (range, 0.6 to 20.1). The confirmed overall response rate was 53% (95% confidence interval [CI], 44 to 62; 6% with a complete response and 47% with a partial response), the median duration of response was 6.7 months (95% CI, 5.6 to 8.6), and the median progression-free survival was 6.8 months (95% CI, 5.6 to 8.1). Primary progression was observed in only 14% of patients. Some patients had a response after receiving vemurafenib for more than 6 months. The median overall survival was 15.9 months (95% CI, 11.6 to 18.3). The most common adverse events were grade 1 or 2 arthralgia, rash, photosensitivity, fatigue, and alopecia. Cutaneous squamous-cell carcinomas (the majority, keratoacanthoma type) were diagnosed in 26% of patients.
  
  
  CONCLUSIONS
  Vemurafenib induces clinical responses in more than half of patients with previously treated BRAF V600-mutant metastatic melanoma. In this study with a long follow-up, the median overall survival was approximately 16 months. (Funded by Hoffmann-La Roche; ClinicalTrials.gov number, NCT00949702.).
authors.affiliation: Vanderbilt-Ingram Cancer Center, Nashville, TN 37232-6307, USA. jeff.sosman@vanderbilt.edu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Kim
authors.forename: Lynn
authors.initials: L
authors.lastname: Schuchter
authors.forename: Rene
authors.initials: R
authors.lastname: Gonzalez
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pavlick
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
authors.forename: Grant A
authors.initials: GA
authors.lastname: McArthur
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hutson
authors.forename: Stergios J
authors.initials: SJ
authors.lastname: Moschos
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
authors.forename: Peter
authors.initials: P
authors.lastname: Hersey
authors.forename: Richard
authors.initials: R
authors.lastname: Kefford
authors.forename: Donald
authors.initials: D
authors.lastname: Lawrence
authors.forename: Igor
authors.initials: I
authors.lastname: Puzanov
authors.forename: Karl D
authors.initials: KD
authors.lastname: Lewis
authors.forename: Ravi K
authors.initials: RK
authors.lastname: Amaravadi
authors.forename: Bartosz
authors.initials: B
authors.lastname: Chmielowski
authors.forename: H Jeffrey
authors.initials: HJ
authors.lastname: Lawrence
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.forename: Keith B
authors.initials: KB
authors.lastname: Nolop
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lee
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Joe
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
mesh_terms: D000328:Adult; D000368:Aged; D018450:Disease Progression; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis / Q000188:drug therapy; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf