First-line vascular endothelial growth factor targeted therapy in renal cell carcinoma: priming the tumor microenvironment for immunotherapy

Abstract

Despite improved outcomes with systemic vascular endothelial growth factor (VEGF)-targeted agents in patients with advanced renal cell carcinoma (RCC), the majority of patients will eventually develop treatment resistance and disease progression. With the emergence of checkpoint inhibitors as potential treatment approaches, studies suggest that ideally combining or sequencing them with VEGF receptor (VEGFR)–tyrosine kinase inhibitors (TKIs) may provide more effective treatments that reduce or delay disease progression. Indeed, preliminary evidence suggests that VEGFR-TKIs can reverse immunosuppressive effects in the tumor microenvironment, potentially enhancing the effects of subsequent immunotherapy with checkpoint inhibitors. However, questions remain regarding the most effective treatment sequences or combinations with VEGFR-TKIs and checkpoint inhibitors. This review discusses the potential role of first-line VEGFR-TKIs in priming the tumor microenvironment for immunotherapy.

Keywords:

• Carcinoma
• renal cell
• vascular endothelial growth factor
• renal cell carcinoma
• tyrosine kinase inhibitor
• immunotherapy
• pazopanib

Transparency

Declaration of funding

This manuscript was funded by Novartis Oncology, Novartis Pharmaceuticals Corporation.

Author contributions: A.A., H.H. and N.T. contributed to conception, design or planning of this review as well as critically reviewing and revising the manuscript for important intellectual content.

Declaration of financial/other relationships

A.A. has disclosed that he has received speaker’s bureau honoraria from BMS, Merck and Pfizer; and research funding from BMS and Merck. H.H. has disclosed that he has received compensation for advisory board activity from BMS, Exelixis, Bayer, Novartis and Pfizer; and clinical trial funding from Merck and BMS. N.T. has disclosed that he has received travel, honoraria and consulting fees from BMS, Exelixis, Nektar, Novartis, Pfizer, Argos and Calithera; and research funding from BMS, Exelixis, Epizyme, Novartis and Miranti.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

Editorial assistance was provided by Chris Ontiveros PhD (ApotheCom, New York) and funded by Novartis Pharmaceuticals Corporation.