Combination of Anti-Angiogenics and Checkpoint Inhibitors for Renal Cell Carcinoma: Is the Whole Greater Than the Sum of Its Parts?

Jonasch, Eric; Atkins, Michael B.; Chowdhury, Simon; Mainwaring, Paul

doi:10.3390/cancers14030644

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Combination of Anti-Angiogenics and Checkpoint Inhibitors for Renal Cell Carcinoma: Is the Whole Greater Than the Sum of Its Parts?

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Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1374, Houston, TX 77030, USA

Department of Oncology, School of Medicine, Georgetown University, Washington, DC 20007, USA

Georgetown Lombardi Comprehensive Cancer Center, Washington, DC 20057, USA

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Department of Medical Oncology, Guy’s and St Thomas’ Hospitals, London SE1 9RT, UK

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Sarah Cannon Research Institute, London W1G 6AD, UK

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Centre for Personalised Nanomedicine, The University of Queensland, Brisbane, QLD 4072, Australia

Author to whom correspondence should be addressed.

Academic Editor: Ke Chen

Cancers 2022, 14(3), 644; https://doi.org/10.3390/cancers14030644

Received: 23 December 2021 / Revised: 21 January 2022 / Accepted: 23 January 2022 / Published: 27 January 2022

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Simple Summary

Checkpoint inhibitors and anti-angiogenic therapies are treatments that slow the progression of renal cell carcinoma, the most common type of kidney cancer. Checkpoint inhibitors and anti-angiogenic therapies work in different ways. Checkpoint inhibitors help to prevent tumors from hiding from the body’s immune system, while anti-angiogenic therapies slow the development of blood vessels that tumours need to help them to grow. Studies have shown that treatment with combination checkpoint inhibitor plus anti-angiogenic therapy can achieve better outcomes for patients with renal cell carcinoma than treatment with anti-angiogenic therapy alone. In this review, we consider how combination checkpoint inhibitor plus anti-angiogenic therapy works, and we review the current literature to identify evidence to inform clinicians as to the most effective way to use these different types of drugs, either one after the other, or together, for maximum patient benefit.

Abstract

Anti-angiogenic agents, such as vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors and anti-VEGF antibodies, and immune checkpoint inhibitors (CPIs) are standard treatments for advanced renal cell carcinoma (aRCC). In the past, these agents were administered as sequential monotherapies. Recently, combinations of anti-angiogenic agents and CPIs have been approved for the treatment of aRCC, based on evidence that they provide superior efficacy when compared with sunitinib monotherapy. Here we explore the possible mechanisms of action of these combinations, including a review of relevant preclinical data and clinical evidence in patients with aRCC. We also ask whether the benefit is additive or synergistic, and, thus, whether concomitant administration is preferred over sequential monotherapy. Further research is needed to understand how combinations of anti-angiogenic agents with CPIs compare with CPI monotherapy or combination therapy (e.g., nivolumab and ipilimumab), and whether the long-term benefit observed in a subset of patients treated with CPI combinations will also be realised in patients treated with an anti-angiogenic therapy and a CPI. Additional research is also needed to establish whether other elements of the tumour microenvironment also need to be targeted to optimise treatment efficacy, and to identify biomarkers of response to inform personalised treatment using combination therapies. View Full-Text

Keywords: vascular endothelial growth factor; immune checkpoint inhibitors; advanced renal cell carcinoma; combination therapy

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MDPI and ACS Style

Jonasch, E.; Atkins, M.B.; Chowdhury, S.; Mainwaring, P. Combination of Anti-Angiogenics and Checkpoint Inhibitors for Renal Cell Carcinoma: Is the Whole Greater Than the Sum of Its Parts? Cancers 2022, 14, 644. https://doi.org/10.3390/cancers14030644

AMA Style

Jonasch E, Atkins MB, Chowdhury S, Mainwaring P. Combination of Anti-Angiogenics and Checkpoint Inhibitors for Renal Cell Carcinoma: Is the Whole Greater Than the Sum of Its Parts? Cancers. 2022; 14(3):644. https://doi.org/10.3390/cancers14030644

Chicago/Turabian Style

Jonasch, Eric, Michael B. Atkins, Simon Chowdhury, and Paul Mainwaring. 2022. "Combination of Anti-Angiogenics and Checkpoint Inhibitors for Renal Cell Carcinoma: Is the Whole Greater Than the Sum of Its Parts?" Cancers 14, no. 3: 644. https://doi.org/10.3390/cancers14030644

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Author Biographies

Eric Jonasch

Eric Jonasch, MD is Professor in the Department of Genitourinary Medical Oncology, Division of Cancer Center at the University of Texas M. D. Anderson Cancer Center in Houston, Texas. Dr. Jonasch is director of the VHL Clinical Center at the MD Anderson Cancer Center and is involved in tissue-based translational research in renal cell carcinoma and VHL disease. He heads a number of investigator-initiated clinical trials and leads the Department of Defense Kidney Cancer Research Consortium. Dr. Jonasch is in charge on an ongoing laboratory research effort evaluating the determinants of response and resistance to therapy in renal cell carcinoma and VHL disease. Dr. Jonasch’s current work focuses on understanding the drivers of renal cell carcinoma tumor ontogeny, and the development of informative models of tumor-microenvironmental interaction. Dr. Jonasch serves as Vice-Chair of the NCCN Kidney Cancer Guideline Panel and is a Board member of the International Kidney Cancer Coalition.

Michael B. Atkins

Dr. Atkins began his career at Tufts before moving to Beth Israel Deaconess Medical Center and being appointed Professor at Harvard Medical School where he served as Deputy Chief of the Division of Hematology/Oncology and leader of the Biologic Therapy and Cutaneous Oncology Programs, Co-PI of the Harvard Skin Cancer SPORE, founding leader of the DF/HCC Kidney Cancer Program and Director of the DF/HCC Kidney Cancer SPORE. In 2012, he moved to Georgetown where he is Deputy Director of the Georgetown Lombardi Comprehensive Cancer Center and William Scholl Professor and Vice Chair of the Department of Oncology. He leads the Lombardi Immunotherapy Initiative. His current research focuses on immunotherapy for melanoma and RCC and biomarkers for response and toxicity. He has published over 450 articles and 5 books and has lectured extensively on these topics. He is past president of SITC and co-Chairs the Melanoma Research Foundation Scientific Advisory Council.

Simon Chowdhury

Simon Chowdhury received his first degree from the University of Cambridge and qualified as a doctor at Guy's and St Thomas' Medical School. He completed his PhD in tumour targeting at University College London and also trained at St George's and The Royal Marsden Hospitals. He is actively involved in clinical trial research into urological cancer, especially prostate cancer. He is on the steering committee for several studies including STAMPEDE, SPARTAN and TITAN studies that have shown potentially practise changing results for men with prostate cancer.

Paul Mainwaring

Dr Mainwaring began his medical training in Sydney before moving to the Royal Marsden NHS Trust, London, completing general medical oncology training in 2002. He was awarded his M.D. for work on apoptosis in breast cancer. Whilst a consultant at Guy’s, King’s and St Thomas’ NHS Trusts, he established several sub-speciality teams and clinical trials programs (colorectal cancer, lymphoma, solid tumours) and continued this work while Director of Medical Oncology at Mater Adult Hospital, Brisbane. He was appointed Adjunct Associate Professor at the Centre for Personalised NanoMedicine, Australian Institute for Bioengineering and Nanotechnology, University of Queensland, developing novel cancer medicine technologies, in addition to senior clinician within the private oncology group ICON. Dr Mainwaring has over 100 publications and serves on several steering committees and advisory boards as well as acting as a reviewer for several journals. He currently co-manages XING Technologies in Brisbane and remains active in clinical practice.

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Combination of Anti-Angiogenics and Checkpoint Inhibitors for Renal Cell Carcinoma: Is the Whole Greater Than the Sum of Its Parts?

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