title: Role of salvage targeted therapy in differentiated thyroid cancer patients who failed first-line sorafenib.
abstract: BACKGROUND
  Sorafenib, a tyrosine kinase inhibitor, is a common first-line therapy for advanced differentiated thyroid cancer (DTC). However, responses are not durable and drug toxicity remains a problem.
  
  
  OBJECTIVE
  The objective of the study was to determine the efficacy of salvage therapy after first-line sorafenib failure.
  
  
  METHODS
  This was a retrospective review at M. D. Anderson Cancer Center from January 2005 to May 2013.
  
  
  METHODS
  The study included patients with metastatic DTC who received salvage therapy after their initial sorafenib failure (group 2). PATIENTS who received first-line sorafenib only (group 1) were evaluated for comparison of overall survival (OS).
  
  
  METHODS
  Progression-free survival, best response, and median OS were measured.
  
  
  RESULTS
  Sixty-four patients with metastatic, radioactive iodine refractory DTC were included; 35 were in group 1 and 25 were in group 2, and the groups were well balanced. Median OS of all 64 patients receiving first line sorafenib was 37 months; median OS was significantly longer with salvage therapy compared with sorafenib alone (58 vs 28 months, P = .013). In group 2, 17 patients were evaluable for best response, although two patients had toxicity with sorafenib, which was discontinued before restaging. Best responses with first-line sorafenib were partial response in 2 of 15 (13%), stable disease in 10 of 15 (67%), and progressive disease in 3 of 15 (20%) patients. With salvage therapy, partial responses were seen in 7 of 17 (41%) and stable disease in 10 of 17 (59%) patients. Median progression-free survival was 7.4 months with first-line sorafenib and 11.4 months with salvage therapy. Salvage therapy included sunitinib (n = 4), pazopanib (n = 3), cabozantinib (n = 4), lenvatinib (n = 3), and vemurafenib (n = 3).
  
  
  CONCLUSIONS
  Other targeted agents are effective salvage treatments after sorafenib failure, despite similar mechanisms of action, and should be offered to patients who are able to receive salvage therapy.
authors.affiliation: Departments of Endocrine Neoplasia and Hormonal Disorders (R.D., S.G.W., N.L.B., M.I.H., C.J., M.A.H., R.V.S., A.K.Y., G.J.C., S.I.S., M.E.C.), Diagnostic Radiology (C.D.), and Biostatistics (M.H.), The University of Texas M. D. Anderson Cancer Center; and Department of Endocrinology, Diabetes, and Metabolism (R.D.), Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Ramona
authors.initials: R
authors.lastname: Dadu
authors.forename: Catherine
authors.initials: C
authors.lastname: Devine
authors.forename: Mike
authors.initials: M
authors.lastname: Hernandez
authors.forename: Steven G
authors.initials: SG
authors.lastname: Waguespack
authors.forename: Naifa L
authors.initials: NL
authors.lastname: Busaidy
authors.forename: Mimi I
authors.initials: MI
authors.lastname: Hu
authors.forename: Camilo
authors.initials: C
authors.lastname: Jimenez
authors.forename: Mouhammad A
authors.initials: MA
authors.lastname: Habra
authors.forename: Rena V
authors.initials: RV
authors.lastname: Sellin
authors.forename: Anita K
authors.initials: AK
authors.lastname: Ying
authors.forename: Gilbert J
authors.initials: GJ
authors.lastname: Cote
authors.forename: Steven I
authors.initials: SI
authors.lastname: Sherman
authors.forename: Maria E
authors.initials: ME
authors.lastname: Cabanillas
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018265:Carcinoma, Papillary, Follicular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D000077157:Sorafenib; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017211:Treatment Failure
chemical_list: D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib