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Expert Rev Anticancer Ther. 2018 Nov;18(11):1113-1124. doi: 10.1080/14737140.2018.1508348. Epub 2018 Aug 21.

The role of tivozanib in advanced renal cell carcinoma therapy.

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a Department of Oncological Medicine , Institut Gustave Roussy , Villejuif , France.
b Medical Oncology , University of Pavia and La Istituti Clinici Scientifici Maugeri , Pavia , Italy.
c Department of Oncology , Cambridge University Health Partners , Cambridge , UK.
d JB Medical Ltd , Sudbury , UK.
e Medical Affairs , EUSA Pharma , Hemel Hempstead , UK.
f Genitourinary Oncology Service, Department of Medicine , Memorial Sloan Kettering Cancer Center , New York , NY , USA.


The efficacy of VEGF-targeting therapies in clinical trials led to their recommendation in clinical guidelines for use across the advanced or metastatic renal cell carcinoma (RCC) treatment landscape, however, tolerability (including off-target effects) has remained a challenge. Tivozanib is a selective inhibitor of all three VEGFRs, with limited off-target interaction, which demonstrates efficacy with improved tolerability relative to multikinase VEGFR-TKIs. Areas covered: Covered here is the clinical development of tivozanib in advanced RCC, including the pivotal Phase III, multicenter, open-label, randomized clinical study comparing tivozanib with sorafenib for the treatment of VEGF- and mTOR therapy-naïve advanced RCC patients. Also covered are ongoing trials, exploring the efficacy and safety of tivozanib in the setting of refractory disease and the utility of tivozanib in combination with checkpoint inhibitors for advanced RCC. Combination of a VEGFR-TKI and immunotherapy is promising in advanced RCC, if the treatment regimens have acceptable tolerability. Here the selectivity of tivozanib may contribute to an acceptable tolerability profile when used in combination therapy. Expert commentary: The approval of tivozanib provides an additional option for the first-line treatment of advanced or metastatic RCC patients in Europe and allows use of a VEGFR-TKI with selectivity for VEGFRs in this setting.


Renal cell carcinoma; TKI; VEGFR; kidney cancer; tivozanib; tyrosine kinase inhibitor

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