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


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.


CONCLUSIONS
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.
Dana-Farber Cancer Institute and Harvard Medical School, Kidney Cancer Program, Boston Toni_Choueiri@dfci.harvard.edu.
T K
TK
Choueiri
Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte.
S K
SK
Pal
Dana-Farber Cancer Institute and Harvard Medical School, Kidney Cancer Program, Boston Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston.
D F
DF
McDermott
Dana-Farber Cancer Institute and Harvard Medical School, Kidney Cancer Program, Boston.
S
S
Morrissey
Clinical Development, Exelixis Inc., South San Francisco.
K C
KC
Ferguson
Clinical Development, Exelixis Inc., South San Francisco.
J
J
Holland
Dana-Farber Cancer Institute and Harvard Medical School, Kidney Cancer Program, Boston.
W G
WG
Kaelin
St Luke's-Roosevelt Hospital Center, New York, USA.
J P
JP
Dutcher
D000328:Adult; D000368:Aged; D000813:Anilides / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000627:therapeutic use*; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
D000813:Anilides; D000970:Antineoplastic Agents; D011725:Pyridines; C558660:cabozantinib
VEGFR-2; c-Met; clinical trial; receptor tyrosine kinase; renal cancer