Avelumab: search for combinations of immune checkpoint inhibition with chemotherapy

ABSTRACT

Introduction

Immune checkpoint inhibition (ICI) has proved successful for selected tumors and a subpopulation of patients. The human monoclonal IgG1 antibody (mAB) avelumab capable of mediating antibody-dependent cytotoxicity (ADCC) lysis is directed to programmed death ligand-1 (PD-L1) of tumor cells and is tested in trials aiming to improve ICI in combination with chemotherapeutic drugs.

Areas covered

This article presents an overview of the current trials to enhance ICI regimens using avelumab in combination with chemotherapeutics, antiangiogenetic drugs, and immunomodulators. Predictive factors for this kind of immunochemotherapy are discussed.

Expert opinion

Clinical data demonstrate that avelumab shows efficacy in cancer patients against Merkel cell carcinoma (MCC), renal cell carcinoma (RCC), and urothelial cancers as single agent. Furthermore, avelumab in combination with axitinib in RCC increases survival and exhibits activity in combination with docetaxel in urothelial carcinoma. However, several other immunochemotherapy trials for ovarian cancer, gastric cancer, and non-small lung cancer (NSCLC) showed no activity due to factors disfavoring administration of immunotherapy combos.

KEYWORDS:

• Avelumab
• immune checkpoint inhibition
• programmed death ligand-1
• antibody-dependent cytotoxicity
• chemotherapy
• anti-angiogenesis
• immunomodulation

Article highlights

• Combinations of immune checkpoint inhibitors with chemotherapeutics are studied to increase antitumor responses.

• Avelumab is directed to PD-L1 and shows single-agent activity against Merkel cell carcinoma, renal cell cancer, and urothelial cancer.

• Avelumab exhibits clinical activity against renal cell cancer in combination with the antiangiogenic TKI axitinib.

• Successful immunochemotherapeutic combinations require at least minimal single-agent ICI activity and a second agent inducing ‘immunogenic’ cell death.

• Active combo agents induce PD-L1 expression, eliminate suppressive Tregs and MDSCs, and enhance effector cell trafficking.

• Although predictive factors are lacking for immunochemotherapeutic combos, the avelumab trials reveal factors associated with active combinations.

This box summarizes key points contained in the article.

Acknowledgments

The author would like to thank Barbara Rath for her contribution to the figure and Adelina Plangger for her review and guidance.

Declaration of interest

The author has no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper is not funded.