title: BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer.
abstract: BACKGROUND
  Mutations of v-raf murine sarcoma viral oncogene homolog B (BRAF) are commonly identified in papillary and anaplastic thyroid carcinoma and are associated with worse prognosis compared with the wild type. BRAF inhibition in papillary thyroid carcinoma cell lines and xenografts inhibits proliferation and decreases downstream phosphorylation. Our objectives were to analyze safety and efficacy of the selective BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid carcinoma.
  
  
  METHODS
  We present the subset of patients with BRAF-mutant thyroid carcinoma enrolled in a larger phase 1 study, the main results of which are reported elsewhere.
  
  
  RESULTS
  Fourteen patients with BRAF(V600E)-mutant thyroid carcinoma were enrolled, of whom 13 (93%) had received prior radioactive iodine. The median duration on treatment was 8.4 months, and seven (50%) patients received treatment for ≥10 months. The most common treatment-related adverse events were skin papillomas (n=8, 57%), hyperkeratosis (n=5, 36%), and alopecia (n=4, 29%), all of which were grade 1. Treatment-related adverse events grade ≥3 included grade 4 elevated lipase and grade 3 elevated amylase, fatigue, febrile neutropenia, and cutaneous squamous cell carcinoma (n=1 for each). Four (29%) partial responses were observed, and nine (64%) patients achieved at least 10% decrease. Only one responder progressed while on the study drug after a response duration of 9.3 months. The other three responders had not progressed, with response duration of 4.6+, 10.4+, and 21.4+ months. With seven (50%) patients showing no progression at the time of study completion, the median progression-free survival was 11.3 months.
  
  
  CONCLUSIONS
  Dabrafenib was well tolerated and resulted in durable responses in BRAF-mutant differentiated thyroid carcinoma patients.
authors.affiliation: 1 Sarah Cannon Research Institute at HealthONE, Denver, Colorado.
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Falchook
authors.forename: Michael
authors.initials: M
authors.lastname: Millward
authors.forename: David
authors.initials: D
authors.lastname: Hong
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.forename: Sarina
authors.initials: S
authors.lastname: Piha-Paul
authors.forename: Steven G
authors.initials: SG
authors.lastname: Waguespack
authors.forename: Maria E
authors.initials: ME
authors.lastname: Cabanillas
authors.forename: Steven I
authors.initials: SI
authors.lastname: Sherman
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.forename: Martin
authors.initials: M
authors.lastname: Curtis
authors.forename: Vicki
authors.initials: V
authors.lastname: Goodman
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002291:Carcinoma, Papillary / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010091:Oximes / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D010091:Oximes; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib