title: A phase I study of cabozantinib (XL184) in patients with differentiated thyroid cancer.
abstract: BACKGROUND
  Cabozantinib targets tyrosine kinases including MET, vascular endothelial growth factor (VEGF) receptor 2, and rearranged during transfection (RET). Differentiated thyroid cancer (DTC) is a tumor type that may be sensitive to cabozantinib. Therefore, we evaluated cabozantinib in a cohort of heavily pretreated patients with metastatic DTC.
  
  
  METHODS
  This single-arm open-label phase I trial assessed the safety, tolerability, and antitumor activity of cabozantinib in DTC patients taking part in a drug-drug interaction study. Adult patients with histologically confirmed metastatic or surgically unresectable DTC (including papillary, follicular, or Hürthle cell) were enrolled. Patients received daily oral dosing of 140 mg cabozantinib. Safety was assessed by evaluation of adverse events (AEs), vital signs, electrocardiograms, laboratory tests, and concomitant medications. Tumor response by magnetic resonance imaging or computed tomography scan was investigator assessed using Response Evaluation Criteria In Solid Tumors (RECIST) v1.0.
  
  
  RESULTS
  The study enrolled 15 patients who had failed standard radioactive iodine therapy. Patients had received a median of two prior systemic agents, and 11 patients (73%) had previously received at least one VEGF pathway inhibiting therapy. Common AEs included diarrhea, nausea, fatigue, and decreased appetite. Partial response was reported in eight patients (53%). Median progression-free survival and median overall survival were not reached.
  
  
  CONCLUSIONS
  Cabozantinib demonstrates a safety profile similar to other multitargeted VEGFR inhibitors in advanced DTC patients. The antitumor activity observed in this study warrants further investigation of cabozantinib in patients with advanced DTC.
authors.affiliation: 1 Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M.D. Anderson Cancer Center , Houston, Texas.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Cabanillas
authors.forename: Marcia S
authors.initials: MS
authors.lastname: Brose
authors.forename: Jaymes
authors.initials: J
authors.lastname: Holland
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Ferguson
authors.forename: Steven I
authors.initials: SI
authors.lastname: Sherman
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000813:Anilides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000556:secondary; D002454:Cell Differentiation; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D006801:Humans; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014481:United States
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C558660:cabozantinib
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