title: Differentiated thyroid cancer: focus on emerging treatments for radioactive iodine-refractory patients.
abstract: BACKGROUND
  The treatment of differentiated thyroid cancer refractory to radioactive iodine (RAI) had been hampered by few effective therapies. Recently, tyrosine kinase inhibitors (TKIs) have shown activity in this disease. Clinical guidance on the use of these agents in RAI-refractory thyroid cancer is warranted.
  
  
  METHODS
  Molecular mutations found in RAI-refractory thyroid cancer are summarized. Recent phase II and III clinical trial data for TKIs axitinib, lenvatinib, motesanib, pazopanib, sorafenib, sunitinib, and vandetinib are reviewed including efficacy and side effect profiles. Molecular targets and potencies of these agents are compared. Inhibitors of BRAF, mammalian target of rapamycin, and MEK are considered.
  
  
  RESULTS
  Routine testing for molecular alterations prior to therapy is not yet recommended. TKIs produce progression-free survival of approximately 1 year (range: 7.7-19.6 months) and partial response rates of up to 50% by Response Evaluation Criteria in Solid Tumors. Pazopanib and lenvatinib are the most active agents. The majority of patients experienced tumor shrinkage with TKIs. Common adverse toxicities affect dermatologic, gastrointestinal, and cardiovascular systems.
  
  
  CONCLUSIONS
  Multiple TKIs have activity in RAI-refractory differentiated thyroid cancer. Selection of a targeted agent should depend on disease trajectory, side effect profile, and goals of therapy.
authors.affiliation: Stanford Cancer Center, Stanford University Medical Center, Stanford, California, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Gruber
authors.affiliation: Stanford Cancer Center, Stanford University Medical Center, Stanford, California, USA colevas@stanford.edu.
authors.forename: A Dimitrios
authors.initials: AD
authors.lastname: Colevas
mesh_terms: D018572:Disease-Free Survival; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000009:adverse effects; D048728:MAP Kinase Kinase Kinase 1 / Q000235:genetics; D009536:Niacinamide / Q000031:analogs & derivatives / Q000235:genetics / Q000627:therapeutic use; D009841:Oligonucleotides; D010671:Phenylurea Compounds / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D000077157:Sorafenib; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology
chemical_list: D007211:Indoles; D007457:Iodine Radioisotopes; D009841:Oligonucleotides; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048728:MAP Kinase Kinase Kinase 1; C519562:imetelstat
keywords: BRAF inhibitors; Follicular thyroid cancer; MEK inhibitors; Papillary thyroid cancer; Radioactive iodine refractory differentiated thyroid cancer; Tyrosine kinase inhibitors