Avelumab and axitinib in the treatment of renal cell carcinoma: safety and efficacy

ABSTRACT

Introduction: The incidence of advanced renal cell carcinoma (RCC) is increasing. Over the last 10 years targeted therapies have led to improved efficacy outcomes for renal carcinoma, including longer survival. However, the majority of patients develop disease progression within a year of initiation of first-line therapy. Recently a number of new regimens have been investigated including the combination of immune checkpoint inhibitors with VEGF inhibitors.

Areas covered: In this review, we assess the efficacy and safety of avelumab/axitinib in treatment-naïve patients with metastatic RCC and compare this combination to other current and emerging treatment regimens. In the Javelin 101 phase III registration trial, avelumab/axitinib demonstrated superior response rates and progression-free survival compared to sunitinib. However, after follow-up of 11.6 months, there was no significant difference in overall survival (OS). Avelumab/axitinib showed a tolerable safety profile. Adverse events were manageable and were in line with expected toxicities from the single agents.

Expert Opinion: Avelumab/axitinib has shown impressive efficacy and a tolerable safety profile in metastatic RCC. The future role of this treatment combination in the rapidly evolving landscape of novel combinations in this disease will have to be defined.

KEYWORDS:

• Avelumab
• axitinib
• advanced renal cell carcinoma
• immunotherapy
• tyrosine kinase inhibitor
• combination treatment

Article Highlights

• Avelumab is an immune checkpoint inhibitor that blocks the PD-1/PD-L1 axis by targeting PD-L1.

• PD-L1 is expressed by tumor cells and thus PD-L1 antagonists, such as avelumab, may have a lower rate of autoimmune-related adverse events than PD-1 antagonists.

• Avelumab is the only immune checkpoint inhibitor in current clinical use in mRCC that induces antibody-dependent cell-mediated cytotoxicity (ADCC) as part of its spectrum of anti-tumor efficacy.

• VEGF receptor tyrosine kinase inhibitors (TKI) have been shown to have immune-modulatory features. Axitinib demonstrated a favorable efficacy/tolerability profile making it a good candidate for use in combination regimens.

• The combination of avelumab and axitinib showed increased efficacy in terms of progression-free survival and response rate compared to the sunitinib control group in all prognostic groups of patients with mRCC in the first-line setting. Further follow-up data will show whether a significant difference in overall survival will emerge.

• Avelumab/axitinib was found to be tolerable and the adverse events (AE) were in line with the toxicity of the single agents. AEs were manageable with supportive therapies and using dose reductions and treatment discontinuation where needed.

• There are several current and emerging treatment regimens that combine immunotherapeutic agents and VEGF inhibitors, including ipilimumab/nivolumab and pembrolizumab/axitinib. The future role of avelumab/axitinib will have to be defined in this rapidly evolving landscape.

Declaration of interest

Lisa Pickering has received honoraria from and has acted in a consulting/advisory role for Bristol-Myers Squibb, Eisai, EUSA Pharma, Glaxo-Smith Kline, Ipsen, MSD, Novartis; and has received research funding from Pierre Fabre. James Larkin has received honoraria from and has acted in a consulting/advisory role for Achilles, AstraZeneca, Boston Biomedical, Bristol-Myers Squibb, Eisai, EUSA Pharma, Glaxo-Smith Kline, Ipsen, Imugene, Incyte, iOnctura, Kymab, Merck Serono, MSD, Nektar, Novartis, Pierre Fabre, Pfizer, Roche, Secarna, Vitaccess; and has received research funding from Bristol-Myers Squibb, MSD, Novartis, Pfizer, Achilles, Aveo, Roche, Nektar, and Covance. 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.