title: Efficacy and tolerability of vemurafenib in patients with BRAF(V600E) -positive papillary thyroid cancer: M.D. Anderson Cancer Center off label experience.
abstract: BACKGROUND
  Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.
  
  
  OBJECTIVE
  To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.
  
  
  METHODS
  A retrospective review at MD Anderson Cancer Center.
  
  
  METHODS
  The best responses were evaluated using RECIST v1.1. A single radiologist reviewed all images. Adverse events (AEs) were evaluated using CTCAE v.4.0.
  
  
  RESULTS
  We identified 17 patients with advanced PTC harboring the BRAF(V600E) mutation who were treated with vemurafenib outside of a clinical trial. Median age at diagnosis was 63 years, and 53% were male. At vemurafenib start, 3 (18%) patients had disease confined to the neck, and 14 (72%) had distant metastases. Tyrosine kinase inhibitors had been previously administered to 4 (24%) patients. Two (12%) patients discontinued vemurafenib because of AEs before restaging. Best response: partial response (PR) in 7/15 (47%) and stable disease (SD) in 8/15(53%) patients. The rate of durable response (PR plus SD ≥ 6 months) was 67%. Median time to treatment failure was 13 months. There was no association between change in thyroglobulin and tumor size. Drug discontinuation, drug interruptions, and dose reductions were needed in 5 (29%), 13 (76%), and 10 (59%) patients, respectively. Most common AEs were fatigue (71%), weight loss (71%), anorexia (65%), arthralgias (59%), hair loss (59%), rash (59%), hand-foot syndrome (53%), calluses (47%), diarrhea (47%), fever (41%), dry mouth (35%), nausea (35%), and verrucous keratosis (35%). Grade ≥ 3 AEs were present in 8 (47%) patients.
  
  
  CONCLUSIONS
  Vemurafenib is a potentially effective and well-tolerated treatment strategy in patients with advanced PTC harboring the BRAF(V600E) mutation. Our results are similar to those reported in a phase II clinical trial and support the potential role of vemurafenib in this patient population.
authors.affiliation: Departments of Endocrine Neoplasia and Hormonal Disorders (R.D., N.L.B., S.G.W., M.A.H., A.K.Y., M.I.H., C.J., S.I.S., M.E.C.), Diagnostic Radiology (K.S.), and Biostatistics (R.B.), The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030.
authors.forename: Ramona
authors.initials: R
authors.lastname: Dadu
authors.forename: Komal
authors.initials: K
authors.lastname: Shah
authors.forename: Naifa L
authors.initials: NL
authors.lastname: Busaidy
authors.forename: Steven G
authors.initials: SG
authors.lastname: Waguespack
authors.forename: Mouhammad A
authors.initials: MA
authors.lastname: Habra
authors.forename: Anita K
authors.initials: AK
authors.lastname: Ying
authors.forename: Mimi I
authors.initials: MI
authors.lastname: Hu
authors.forename: Roland
authors.initials: R
authors.lastname: Bassett
authors.forename: Camilo
authors.initials: C
authors.lastname: Jimenez
authors.forename: Steven I
authors.initials: SI
authors.lastname: Sherman
authors.forename: Maria E
authors.initials: ME
authors.lastname: Cabanillas
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D056687:Off-Label Use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016896:Treatment Outcome; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf