The 2021 Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibitor-based Combination Therapies for Treatment-naive Metastatic Clear-cell Renal Cell Carcinoma Are Standard of Care.

Abstract

The recent randomized controlled phase III CLEAR trial results are the last to complement immune checkpoint inhibitor (ICI)-based doublet combination therapies for treatment-naïve metastatic clear-cell renal cell carcinoma. The CLEAR trial demonstrated an improved progression-free survival (PFS), overall survival (OS), and an objective response rate (ORR) benefit for the combination of lenvatinib plus pembrolizumab over sunitinib. The CheckMate-9ER trial update demonstrated an ongoing PFS, OS, and quality-of-life benefit for cabozantinib plus nivolumab over sunitinib as did the update of Keynote-426 for axitinib plus pembrolizumab in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups. In the IMDC intermediate- and poor-risk groups, the CheckMate-214 trial of ipilimumab plus nivolumab confirmed the OS benefit with a PFS plateauing after 30 months. The RCC Guidelines Panel recommends three tyrosine kinase inhibitors + ICI combinations of axitinib plus pembrolizumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab across all IMDC risk groups in advanced first-line RCC, and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate- and poor-risk groups. PATIENT SUMMARY: New data from combination trials with immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit for lenvatinib plus pembrolizumab, cabozantinib plus nivolumab (with improved quality-of-life), axitinib plus pembrolizumab, and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.

• Authors: Jens Bedke, Laurence Albiges, Umberto Capitanio, Rachel H Giles, Milan Hora, Thomas B Lam, Börje Ljungberg, Lorenzo Marconi, Tobias Klatte, Alessandro Volpe, Yasmin Abu-Ghanem, Saeed Dabestani, Sergio Fernández Pello, Fabian Hofmann, Teele Kuusk, Rana Tahbaz, Thomas Powles, Axel Bex
• Journal: European urology (Eur Urol) Vol. 80 Issue 4 Pg. 393-397 (10 2021) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 34074559 (Publication Type: Editorial)
• Copyright: Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Immune Checkpoint Inhibitors
• Ipilimumab
• Nivolumab
• Axitinib
• Sunitinib

Topics

• Axitinib
• Carcinoma, Renal Cell (drug therapy)
• Humans
• Immune Checkpoint Inhibitors
• Ipilimumab (therapeutic use)
• Kidney Neoplasms (drug therapy)
• Nivolumab (therapeutic use)
• Standard of Care
• Sunitinib (therapeutic use)
• Urology