Tivozanib for the treatment of advanced renal cell carcinoma

ABSTRACT

Introduction

Renal cell carcinoma (RCC) accounts for 2.4% of cancers, with clear cell kidney cancer being the most common histologic subtype. Despite recent therapeutic advances, the prognosis for patients with advanced disease remains poor, with a 5-year survival rate of only 13.9% reported in the United States. Tivozanib is a novel inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR)-1, -2, and -3 and has recently been approved by the US FDA for use in patients with relapsed or recurrent advanced RCC following two or more prior systemic therapies.

Areas covered

Here, the authors provide a review focusing on the development of tivozanib, compare tivozanib to other agents in the VEGFR inhibitor class, detail how tivozanib fits into current treatment landscape, and describe ongoing studies involving this agent.

Expert opinion

Given tivozanib’s excellent safety profile and demonstrated clinical benefit in patients with pretreated disease, tivozanib is likely to be heavily utilized in the later-line setting. The ongoing TINIVO-2 study may further impact the treatment landscape by evaluating the use of tivozanib plus nivolumab in patients who have progressed on an immune checkpoint inhibitor.

KEYWORDS:

• Tivozanib
• VEGF inhibitor
• renal cell carcinoma
• recurrent
• advanced
• kidney cancer

Article highlights

• The prognosis for advanced renal cell carcinoma (RCC) remains poor, with a 5-year survival rate of only 13.9%

• Tivozanib is a potent and selective inhibitor of VEGFR -1, -2 and -3.

• A phase III trial demonstrated that Tivozanib had superior progression-free survival when compared to sorafenib in patients with advanced RCC who had progressed on two or three prior systemic regimens.

• Tivozanib is the only agent approved in the United States specifically for the treatment of advanced RCC which has progressed on two or more prior systemic therapies.

• The TiNivo 2 is currently comparing the combination of tivozanib plus nivolumab to tivozanib alone in patients with advanced RCC who had previously progressed on immune checkpoint inhibitor therapy.

Declaration of interest

J Chatzkel and B Ramnaraign have both received research support from Aveo and Genentech. Meanwhile, G. Sonpavde has served on the advisory boards of Bristol-Myers Squibb, Genentech, EMD Serono, Merck & Co, Sanofi, Seattle Genetics/Astellas, AstraZeneca, Exelixis, Janssen Pharmaceuticals, Bicycle Therapeutics, Pfizer, Immunomedics/Gilead Sciences, Scholar Rock, G1 Therapeutics, Eli Lilly and Company/Loxo Oncology and Infinity Pharmaceuticals. Furthermore, he has received research support via his institution from Sanofi, AstraZeneca, Immunomedics/Gilead Sciences QED, Predicine, Lucence and Bristol-Myers Squibb and taken part on the steering committees of studies for Bristol-Myers Squibb, Bavarian Nordic, Seattle Genetics, QED and G1 Therapeutics (all unpaid) as well as AstraZeneca, EMD Serono, and Debiopharm (paid). He has served on the data safety monitoring committee for Mereo and has received travel costs from Bristol-Myers Squibb and AstraZeneca. Furthermore, he has feed editorial/writing fees from UpToDate and Elsevier as well as speaking fees from the Physicians Education Resource (PER), Onclive, Research to Practice, Medscape, the Cancer Network and the Master Lecture Series (MLS). 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

One review declares that they acted as a consultant and/or speaker for the following companies manufacturing and/or testing drugs for the treatment of renal cancer: Angelini, AstraZeneca, Bristol-Myers Squibb, Eisai, EUSA Pharma, Ipsen and Merck & Co/Merck Sharp and Dohme. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.