A phase I study of cabozantinib (XL184) in patients with renal cell cancer
Mené sur 25 patients atteints d'un carcinome à cellules rénales et en échec thérapeutique, cet essai de phase I évalue la toxicité et l'activité antitumorale du cabozantinib, un inhibiteur des tyrosines kinases MET et VEGF
Background : Cabozantinib targets tyrosine kinases including 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 7 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 TKIs in advanced RCC patients. Further evaluation of cabozantinib in RCC is warranted.
Annals of Oncology 2014