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Ann Oncol. 2014 Aug;25(8):1603-8. doi: 10.1093/annonc/mdu184. Epub 2014 May 14.

A phase I study of cabozantinib (XL184) in patients with renal cell cancer.

Author information

1
Dana-Farber Cancer Institute and Harvard Medical School, Kidney Cancer Program, Boston Toni_Choueiri@dfci.harvard.edu.
2
Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte.
3
Dana-Farber Cancer Institute and Harvard Medical School, Kidney Cancer Program, Boston Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston.
4
Dana-Farber Cancer Institute and Harvard Medical School, Kidney Cancer Program, Boston.
5
Clinical Development, Exelixis Inc., South San Francisco.
6
St Luke's-Roosevelt Hospital Center, New York, USA.

Abstract

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.

KEYWORDS:

VEGFR-2; c-Met; clinical trial; receptor tyrosine kinase; renal cancer

PMID:
24827131
PMCID:
PMC6279111
DOI:
10.1093/annonc/mdu184
[Indexed for MEDLINE]
Free PMC Article

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