An evaluation of avelumab for the treatment of genitourinary tumors

ABSTRACT

Introduction

The immune checkpoint inhibitors (ICI) programmed cell death protein and ligands 1 (PD1- and PD-L1) as well as cytotoxic T-lymphocyte-associated protein 4 have demonstrated clinical efficacy in genitourinary cancer. While different ICI exist, focus of the current study work was to evaluate the PD-L1 antibody avelumab within this framework of ICI.

Areas covered

The manuscript reviews the pharmacological characteristics and preclinical and clinical data of avelumab in the treatment for advanced or metastatic genitourinary cancers. It highlights its respective clinical relevance and special features in the context of the other available ICI.

Expert opinion

Avelumab has shown promising antitumor activity and a manageable safety profile in patients with mRCC and mUC as mono- and combination therapy. The approach of an avelumab maintenance therapy in mUC is promising and could become part of future clinical practice. Results of ICI used in the neoadjuvant or adjuvant setting are eagerly awaited. Avelumab’s uniqueness is its capacity to enhance antibody-dependent cell-mediated cytotoxicity. Because of this, currently ongoing clinical trials investigate the combination of avelumab with other immune modulating agents like IL-12 and IL-15. Thereby, it can be assumed that avelumab will have an ongoing role in the treatment of patients with genitourinary tumors.

KEYWORDS:

• Avelumab
• genitourinary tumors
• immune checkpoint inhibitor
• pd-L1
• renal cell carcinoma
• urothelial cancer

Article highlights

• Avelumab has shown promising antitumor activity and a manageable safety profile in urological tumor entities.

• Avelumab in combination with axitinib is approved for first-line therapy in mRCC patients of all IMDC risk groups.

• Avelumab could be a promising option in the neo-adjuvant and adjuvant setting as well as maintenance therapy.

• Currently ongoing clinical trials with avelumab include also patients with prostate and penile cancer

• In contrast to other anti-PD-1 or PD-L1 antibodies, avelumab can additionally mediate cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) as shown in vitro.

• Unfortunately, to date, there is no predictive biomarker for avelumab available.

This box summarizes key points contained in the article.

Declaration of interest

J Bedke reports Consultancies and Speaker´s Bureau from BMS; Eisai, EUSA, Ipsen, Novartis, MSD, Pfizer, Roche and study participation with institutional funding: Bayer, BMS; Eisai, Exelixis, Ipsen, Novartis, MSD, Pfizer, Roche. A Stenzl reports Consultancies and Speaker´s Bureau: Ipsen, Roche, Janssen, BMS, Alere, Stebabiotech, Synergo, Ferring, Astellas, Amgen, Sanofi Aventis, CureVac and study participation or research grants with institutional funding: Johnson & Johnson, Roche, Cepheid, Amgen, Bayer, CureVac, GemeDx biotechnologies GmbH, Novartis, Karl Storz, immatics biotechnologies GmbH. 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 relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.