Cabozantinib and nivolumab as first-line treatment in advanced renal cell carcinoma

ABSTRACT

Introduction

In the last decade, there have been substantial changes in the management of metastatic renal cell carcinoma (mRCC) with combined regimens with immune checkpoint inhibitors (ICI) replacing targeted therapies. These combined regimens include the combination of cabozantinib plus nivolumab.

Areas covered

Here, we provide an overview of clinical trials evaluating the combination of cabozantinib and nivolumab and the current clinical data on mechanism of action, pharmacokinetics, efficacy, and safety profile.

Expert opinion

Dual immune checkpoint inhibition with nivolumab and ipilimumab as well as the combination of a vascular endothelial growth factor (VEGF) inhibitor and an immune checkpoint inhibitor have shown to improve outcomes in phase III trials in comparison to sunitinib (axitinib plus pembrolizumab, axitinib plus avelumab, bevacizumab plus atezolizumab, cabozantinib plus nivolumab, lenvatinib plus pembrolizumab). However, to date, there are no head-to-head trials comparing these new combination therapies and no biomarkers are available to guide the optimal choice of first line therapy.

KEYWORDS:

• Cabozantinib
• immune checkpoint inhibitors
• metastatic renal cell carcinoma
• multiple tyrosine kinase inhibitors
• nivolumab

Article highlights

• Upfront immunotherapy-based combination has transformed the management of first-line treatment of patients with metastatic renal cell carcinoma (mRCC).

• The combination of cabozantinib and nivolumab has shown increased efficacy in terms of progression-free survival, response rate and overall survival compared to the sunitinib control group in all prognostic groups of patients with mRCC in the first-line setting.

• The advantage of this combination is confirmed regardless of PD-L1 expression and the presence of a sarcomatoid component.

• Cabozantinib/nivolumab was found to be tolerable and the adverse events were in line with the toxicity of the single agents.

• Adverse events were manageable with supportive therapies, dose reductions, and treatment discontinuation.

Declaration of interest

MG Vitale has served in an advisory role and has received honoraria for speeches and travel support from Novartis, Pfizer, Ipsen, Merck Sharp & Dohme, Bristol Myers Squibb, Astellas, Amgen, Janssen, GSK. R Sabbatini has served in an advisory role and has received honoraria for speeches and travel support from Novartis, Pfizer, Ipsen, Merck Sharp & Dohme, Bristol Myers Squibb, Astellas, Amgen, Janssen, GSK, Clovis. C Baldessari has received honoraria for speeches and travel support from Clovis, Astellas and Ipsen. 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

This paper received no funding