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A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
A phase I study of cabozantinib (XL184) in patients with renal cell cancer
T K Choueiri1, S K Pal2, D F McDermott3
1Dana-Farber Cancer Institute and Harvard Medical School, Kidney Cancer Program, Boston Toni_Choueiri@dfci.harvard.edu.
Background:
Cabozantinib targets tyrosine kinases including the hepatocyte growth factor receptor (MET) and vascular endothelial growth factor (VEGF) receptor 2, which are important drug targets in renal cell carcinoma (RCC).
Patients And Methods:
This single-arm open-label phase I trial evaluated the safety and tolerability of cabozantinib in heavily pretreated patients with metastatic clear cell RCC.
Results:
The study enrolled 25 RCC patients for whom standard therapy had failed. Patients received a median of two prior systemic agents, and most patients had previously received at least one VEGF pathway inhibiting therapy (22 patients [88%]). Common adverse events included fatigue, diarrhea, nausea, proteinuria, appetite decreased, palmar-plantar erythrodysesthesia, and vomiting. Partial response was reported in seven patients (28%). Median progression-free survival was 12.9 months, and median overall survival was 15.0 months.
Conclusion:
Cabozantinib demonstrates preliminary anti-tumor activity and a safety profile similar to that seen with other multitargeted VEGFR tyrosine kinase inhibitors in advanced RCC patients. Further evaluation of cabozantinib in RCC is warranted. ClinicalTrials.gov identifier: NCT01100619.
Insights
Cabozantinib shows promise in treating advanced renal cell carcinoma (RCC) by targeting key growth factors. The drug demonstrated anti-tumor activity and a manageable safety profile in heavily pretreated patients.
Area of Science:
- Oncology
- Pharmacology
Background:
- Renal cell carcinoma (RCC) is a significant health concern.
- Hepatocyte growth factor receptor (MET) and vascular endothelial growth factor (VEGF) receptor 2 are key targets in RCC treatment.
- Cabozantinib is a novel tyrosine kinase inhibitor targeting MET and VEGF receptors.
Purpose of the Study:
- To evaluate the safety and tolerability of cabozantinib.
- To assess the preliminary anti-tumor activity of cabozantinib.
- To investigate cabozantinib in patients with advanced renal cell carcinoma.
Main Methods:
- A single-arm, open-label, phase I clinical trial was conducted.
- The study included heavily pretreated patients with metastatic clear cell RCC.
- Patients received cabozantinib after standard therapies failed.
Main Results:
- Partial response was observed in 28% of patients.
- Median progression-free survival was 12.9 months.
- Median overall survival was 15.0 months.
- Common adverse events included fatigue, diarrhea, and nausea.
Conclusions:
- Cabozantinib exhibits preliminary anti-tumor activity in advanced RCC.
- The drug's safety profile is consistent with other multitargeted VEGFR tyrosine kinase inhibitors.
- Further investigation of cabozantinib for RCC is warranted.
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