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A phase I study of cabozantinib (XL184) in patients with differentiated thyroid cancer
Maria E Cabanillas1, Marcia S Brose, Jaymes Holland
11 Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M.D. Anderson Cancer Center , Houston, Texas.
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.
Insights
Cabozantinib showed antitumor activity in advanced differentiated thyroid cancer (DTC) patients who had failed prior therapies. This tyrosine kinase inhibitor (TKI) demonstrated a manageable safety profile, supporting further investigation in metastatic DTC.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Differentiated thyroid cancer (DTC) is a malignancy that may respond to targeted therapies.
- Cabozantinib is a tyrosine kinase inhibitor (TKI) targeting MET, vascular endothelial growth factor (VEGF) receptor 2, and rearranged during transfection (RET).
- This study evaluated cabozantinib in heavily pretreated metastatic DTC patients.
Purpose of the Study:
- To assess the safety, tolerability, and antitumor activity of cabozantinib.
- To evaluate cabozantinib in patients with advanced differentiated thyroid cancer (DTC).
Main Methods:
- A single-arm, open-label, phase I trial was conducted.
- 15 adult patients with metastatic or unresectable DTC received daily oral cabozantinib (140 mg).
- Safety was assessed via adverse events, vital signs, and laboratory tests; tumor response was evaluated using RECIST v1.0.
Main Results:
- 15 patients with advanced DTC, pretreated with systemic agents and VEGF inhibitors, were enrolled.
- Common adverse events included diarrhea, nausea, fatigue, and decreased appetite.
- Partial response was observed in 8 patients (53%); median progression-free and overall survival were not reached.
Conclusions:
- Cabozantinib exhibits a safety profile consistent with other multi-targeted VEGFR inhibitors in advanced DTC.
- The observed antitumor activity suggests cabozantinib warrants further investigation for advanced DTC treatment.
