title: Marked, homogeneous, and early [18F]fluorodeoxyglucose-positron emission tomography responses to vemurafenib in BRAF-mutant advanced melanoma.
abstract: OBJECTIVE
  Imaging with [(18)F]fluorodeoxyglucose (FDG) -positron emission tomography (PET) allows early recognition of a response to agents that target key driver mutations in human cancer. We aimed to determine the metabolic response rate to vemurafenib in patients with advanced BRAF-mutant melanoma.
  
  
  METHODS
  Baseline and day 15 FDG-PET was evaluated in 31 patients with advanced melanoma treated in a phase I study of dose escalation of vemurafenib (PLX06-02), which included four patients treated at subtherapeutic doses and 24 patients treated at 960 mg twice a day, which is the maximum-tolerated dose of vemurafenib.
  
  
  RESULTS
  All 27 patients treated at potentially therapeutic levels had at least a partial metabolic response, and three patients achieved a complete metabolic response. In the 27 patients, there was an 80% ± 3% reduction in the maximum standardized uptake value (SUVmax) of target lesions and an 87% ± 3% decrease in the percentage of injected dose (%ID) in all identified disease sites. There was a positive correlation between %ID in all identified disease and target-lesion SUVmax (r(2) = 0.66; P < .001) that indicated a significant homogeneity of the response between lesions in individual patients. Although no relationship was found between the reduction in target lesion SUVmax and best response according to RECIST (Response Evaluation Criteria in Solid Tumors), there was a trend for patients with greater reductions in uptake of FDG to have longer progression-free survival.
  
  
  CONCLUSIONS
  FDG-PET is a useful marker of an early biologic response to vemurafenib. Little variability in PET response was found between lesions in individual patients, which suggested minimal intrapatient molecular heterogeneity. FDG-PET is a useful tool for the evaluation of the biologic impact of inhibiting mutant BRAF and may allow for the more effective development of novel agents.
authors.affiliation: Peter MacCallum Cancer Centre, Melbourne, VIC 8006, Australia. grant.mcarthur@petermac.org
authors.forename: Grant A
authors.initials: GA
authors.lastname: McArthur
authors.forename: Igor
authors.initials: I
authors.lastname: Puzanov
authors.forename: Ravi
authors.initials: R
authors.lastname: Amaravadi
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
authors.forename: Paul
authors.initials: P
authors.lastname: Chapman
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Kim
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lee
authors.forename: Keith
authors.initials: K
authors.lastname: Nolop
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
authors.forename: Jason
authors.initials: J
authors.lastname: Callahan
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D014408:Biomarkers, Tumor / Q000378:metabolism; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D042241:Early Diagnosis; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008875:Middle Aged; D008991:Monitoring, Physiologic; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography / Q000379:methods; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012878:Skin Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome; D000077484:Vemurafenib
chemical_list: D014408:Biomarkers, Tumor; D007211:Indoles; D013449:Sulfonamides; D019788:Fluorodeoxyglucose F18; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf