Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Jan 24, 2022; 13(1): 1-8
Published online Jan 24, 2022. doi: 10.5306/wjco.v13.i1.1
Update on the treatment of metastatic renal cell carcinoma
Rafael Antonio Medina López, Ines Rivero Belenchon, Javier Mazuecos-Quirós, Carmen Belén Congregado-Ruíz, Felipe Couñago
Rafael Antonio Medina López, Javier Mazuecos-Quirós, Carmen Belén Congregado-Ruíz, Department of Urology and Nephrology, Virgen del Rocío University Hospital, Biomedical Institute of Seville/CSIC/University of Seville, Sevilla 41013, Spain
Ines Rivero Belenchon, Department of Urology and Nephrology, Virgen del Rocío University Hospital, Seville 41005, Spain
Felipe Couñago, Radiation Oncology, Hospital Universitario Quirónsalud, Hospital La Luz, Universidad Europea de Madrid, Madrid 28223, Spain
Author contributions: Medina López RA, Rivero Belenchon I, Mazuecos-Quirós J, Congregado-Ruíz CB, and Couñago F contributed equally to the manuscript; all authors have read and approved the final manuscript.
Conflict-of-interest statement: Dr. Rivero Belenchon has nothing to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ines Rivero Belenchon, MD, Staff Physician, Department of Urology and Nephrology, Virgen del Rocío University Hospital, Manuel Siurot s/n, Seville 41005, Spain. ines.rivero.belenchon@gmail.com
Received: December 25, 2020
Peer-review started: December 25, 2020
First decision: September 29, 2021
Revised: October 5, 2021
Accepted: January 10, 2022
Article in press: January 10, 2022
Published online: January 24, 2022

Metastatic renal cell cancer (mRCC) management has undergone a paradigm shift in recent decades. The first revolution came with the emergence of vascular endothelial growth factor inhibitors; there was a second wave with the unprecedented success of checkpoint inhibitors, and then the latest approach, which is becoming the new care standard in mRCC, of combining these two strategies in different ways. Updated results of Checkmate-214 after 42 mo of follow-up were consistent with previously published results showing the superiority of nivolumab/ipilimumab over sunitinib in progression free survival (PFS), overall survival (OS), and objective response rate (ORR) in intermediate and high-risk patients. However, several studies presented at the American Society of Clinical Oncology 2020 suggested that the best place, and so far, the only one for nivolumab/ipilimumab is the frontline setting. The update on Keynote-426 after 23 mo of follow-up showed no superiority of pembroli-zumab/axitinib over sunitinib in favorable-risk mRCC, suggesting that it should no longer be the first line of choice in low-risk patients. Finally, the phase III Checkmate 9ER trial results revealed the superiority of nivolumab/cabozantinib vs sunitinib in PFS, OS, and ORR, providing a new first-line option among all International Metastatic RCC Database Consortium risk patients. Some phase II clinical trials also presented this year showed promising results with new combination therapies such as nivolumab/sitravatinib, cabozantinib/atezolizumab, and lenvatinib/pembrolizumab, providing promising grounds upon which to start phase III studies. In addition, other works are using novel therapeutic agents with different mechanisms of action, including telaglenastat (a glutaminase inhibitor), entinostat [an inhibitor of histone deacetylases (HDACs)], and olaparib and talazoparib, poly(ADP-ribose) polymerase inhibitors widely used in other tumors. However, some questions regarding mRCC management still need to be addressed, such as head-to-head comparisons between the current options, treatment sequencing, non-clear cell mRCC, and the role of biomarkers to ascertain the best treatment choice.

Keywords: Metastatic renal cell carcinoma, Systemic treatment, Immune checkpoint inhibitors, Antiangiogenic, Update, Biomarkers

Core Tip: Kidney cancer therapeutics is a fast-changing field, and the outcome of metastatic renal cell carcinoma (mRCC) has thus improved considerably in recent years with the introduction of different combinations of immune checkpoint and vascular endothelial growth factors inhibitors. State-of-the-art systemic therapy regimens must be addressed to be in a position to offer patients the best options. The aim of this editorial is to provide an update and insight on future directions on mRCC management.