A Phase I Study of Cabozantinib (XL184) in Patients with Differentiated Thyroid Cancer

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 Hurthle 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 Crit...