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Review
. 2016 Sep 23:9:5825-5837.
doi: 10.2147/OTT.S97397. eCollection 2016.

Clinical use of cabozantinib in the treatment of advanced kidney cancer: efficacy, safety, and patient selection

Steven S Yu  1 , David I Quinn  1 , Tanya B Dorff  1
Affiliations
Review

Clinical use of cabozantinib in the treatment of advanced kidney cancer: efficacy, safety, and patient selection

Steven S Yu et al. Onco Targets Ther. .

Abstract

Clear cell (cc) renal cell carcinoma (RCC) is the most common type of cancer found in the kidney accounting for ~90% of all kidney cancers. In 2012, there were ~337,000 new cases of RCC diagnosed worldwide with an estimated 143,000 deaths, with the highest incidence and mortality in Western countries. Despite improvements in cancer control achieved with VEGF- and mTOR-targeted therapy for RCC, progression remains virtually universal and additional therapies are needed. The pivotal results of the METEOR trial led to cabozantinib's designation as a breakthrough drug by the US Food and Drug Administration and its approval for treatment of advanced RCC in 2016. Subsequent data from the CABOSUN trial, where caboxantinib is compared with sunitinib, will provide information on the relative activity of cabozantinib as first-line therapy for ccRCC. We review the development of cabozantinib in advanced RCC and its role in the treatment landscape for advanced RCC.

Keywords: cabozantinib; clear cell carcinoma; kidney cancer; renal cell carcinoma; tyrosine kinase inhibitor.

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Figures

Figure 1
Figure 1
Angiogenesis is controlled by growth factors such as vascular endothelial growth factor and hepatocyte growth factor, which increase endothelial cell proliferation, migration, and survival. Note: Adapted with permission from Exelixis, Inc. © 2016.
Figure 2
Figure 2
VEGF, HIF1, and MET are upregulated in hypoxic environments to promote survival by stimulating angiogenesis or facilitating migration away from the hypoxic zone. Note: Adapted with permission from Exelixis, Inc. © 2016. Abbreviations: AR, androgen receptor; NSCLC, non-small cell lung cancer.
Figure 3
Figure 3
Cabozantinib binds to and inhibits tyrosine kinases implicated in tumor pathobiology involved in angiogenesis including VEGF, MET, and AXL to block motility, invasion, metastasis, and angiogenesis. Note: Adapted with permission from Exelixis, Inc. © 2016. Abbreviation: TKIs, tyrosine kinase inhibitors.
Figure 4
Figure 4
Cabozantinib provides dual inhibition of MET and VEGFR2 preventing the MET pathway from acting as an alternative pathway in the development of VEGF TKI resistance.
See this image and copyright information in PMC

References

    1. Ferlay J, Soerjomataram I, Ervik M, et al. [homepage on the Internet] GLOBOCAN 2012 v11, Cancer Incidence and Mortality Worldwide: IARC CancerBase No 11 [Internet] Lyon, France: International Agency for Research on Cancer; 2014. [Accessed January 16, 2015]. Available from: http://globocan.iarc.fr.
    1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. - PubMed
    1. Cancer.net [webpage on the Internet] Kidney cancer. [Accessed July 17, 2012]. Available from: http://www.cancer.net/patient/Cancer+Types/Kidney+Cancer?sectionTitle=Ri....
    1. American Cancer Society Detailed Guide: Kidney Cancer. (Adult) – Renal Cell Carcinoma. 2012. [Accessed July 17, 2012]. Available from: http://www.cancer.org/acs/groups/cid/documents/webcontent/003107-pdf.
    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5. - PubMed