The role of tivozanib in advanced renal cell carcinoma therapy

ABSTRACT

Introduction: 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.

KEYWORDS:

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

Acknowledgments

The authors would like to thank Rory Elsome of TVF Communications for their medical writing support.

Declaration of interest

B Escudier has received consulting fees from Bayer, Pfizer, and Novartis; and honoraria from Bayer, Roche, Pfizer, Genentech, Novartis, and AVEO. J Morgan and D Gibson are both employees of EUSA Pharma (UK) Ltd. J Belsey has receive consultancy payments from EUSA Pharma for data analysis services. C Porta reports personal fees from Novartis, Pfizer, Bristol Myers Squibb, Ipsen, EUSA Pharma, Eisai, Janssen, and Peloton, as well as an institutional research grant from Pfizer. R Motzer reports consulting fees from Pfizer, Eisai, Novartis, Genentech/Roche, Merck, as well as funding to Memorial Sloan Keterring Cancer Center from Bristol Myers Squibb, Pfizer, Novartis, Genentech/Roche, and Eisai. T Eisen is employed by AstraZeneca and has stock in AstraZeneca. He has received research support from AstraZeneca, Bayer, and Pfizer and has received honoraria for participation in advisory boards from AVEO and Astellas. 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.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

EUSA Pharma (UK) Ltd funded the development of this manuscript.