Cabozantinib for the treatment of kidney cancer

ABSTRACT

Introduction: Cabozantinib is a small molecule tyrosine kinase inhibitor that initially showed activity in medullary thyroid cancer and was recently approved by the Food and Drug Administration for the treatment of metastatic renal cell carcinoma after progression on first line therapy.

Areas covered: In the METEOR trial, cabozantinib demonstrated significantly improved efficacy in all three endpoints; response rates, progression free survival and overall survival in a randomized trial with everolimus as an active comparator. Cabozantinib also showed activity in the front line setting in RCC within the CABOSUN trial. The study randomized untreated metastatic RCC patients to either cabozantinib or sunitinib and the former showed improved progression free survival which was the primary endpoint. The future holds promise for indications in other malignancies, given the preliminary efficacy and unique mechanism of action of cabozantinib.

In this review we address the mechanism of action, pharmacodynamics and pharmacokinetics of cabozantinib, and also review the development pathway of this agent in the treatment of advanced renal cell carcinoma. The potential benefit in specific patient populations, such as poor risk patients and bone metastases subgroups is also discussed.

Expert commentary: The clinical applications of cabozantinib will be addressed within the context of the current competitive therapeutic landscape of RCC.

KEYWORDS:

• Cabozantinib
• renal cell carcinoma
• targeted therapy
• RCC
• METEOR
• MET
• CABOSUN

Declaration of interest

U Vaishampayan has received research support, and honoraria from Exelixis Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Information Resources

1. METEOR Trial report: Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1814-23. The registration trial that established the efficacy of Cabozantinib as compared to everolimus in pretreated advanced kidney cancer .

2. CABOSUN: Choueiri TK, Halabi S, Sanford BL, et al. Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: The Alliance A031203 CABOSUN trial. Journal of Clinical Oncology. 14 November 2016:JCO-2016. Phase II randomized trial of Cabozantinib compared to sunitinib in the front line treatment of advanced renal cell carcinoma.

Additional information

Funding

The authors were supported in part by National Cancer Institute Grant P30 CA022453