The efficacy demonstrated by 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 that compared 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.
Expert review of anticancer therapy. 2018 Aug 07 [Epub ahead of print]
Bernard Escudier, Camillo Porta, Tim Eisen, Jonathan Belsey, Damilola Gibson, Jonathan Morgan, Robert Motzer
a Institut Gustave Roussy , Villejuif , France., b University of Pavia and IRCCS San Matteo University Hospital Foundation , Pavia , Italy., c Cambridge University Health Partners , Cambridge , UK., d JB Medical Ltd , Sudbury , UK., e EUSA Pharma , Hemel Hempstead , UK., f Memorial Sloan Kettering Cancer Center , New York , USA.