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Review
. 2022 Jun 10;14(12):2867.
doi: 10.3390/cancers14122867.

Metastatic Clear-Cell Renal Cell Carcinoma in the Era of Immune Checkpoint Inhibitors: Therapies and Ongoing Trials

Tony Zibo Zhuang  1 , Katherine Case  1 , Timothy Anders Olsen  1 , Jacqueline T Brown  2   3 , Bradley C Carthon  2   3 , Omer Kucuk  2   3 , Jamie Goldman  2   3 , Wayne Harris  2   3 , Mehmet Asim Bilen  2   3 , Bassel Nazha  2   3
Affiliations
Review

Metastatic Clear-Cell Renal Cell Carcinoma in the Era of Immune Checkpoint Inhibitors: Therapies and Ongoing Trials

Tony Zibo Zhuang et al. Cancers (Basel). .

Abstract

Immune checkpoint inhibitors (ICI) are now the bedrock for the treatment of metastatic renal cell carcinoma (RCC). Clear cell RCC (ccRCC) represents the most common subtype of this malignancy. Herein, we explore the therapeutic landscape of ccRCC by discussing the standard of care whose backbone consists of immune checkpoint inhibitors (ICI) and vascular endothelial growth factor inhibitors (VEGF). For ccRCC, pembrolizumab-axitinib, pembrolizumab-lenvatinib, and avelumab-axitinib or nivolumab-cabozantinib are now FDA-approved frontline options for all risk groups while nivolumab-ipilimumab is reserved for intermediate- and poor-risk groups. Monotherapy with pembrolizumab or nivolumab is a potential option for patients who are unable to take VEGFR-tyrosine kinase inhibitors. While outcomes have improved with the adoption of ICI therapies, many patients develop therapy-resistant disease, creating an unmet need for further investigation. The efficacy of novel therapies as well as novel combinations in the post-ICI era is unclear. This review summarizes the most significant clinical trials involving dual ICI/ICI and ICI/VEGFR therapies, in addition to other selected combination therapies that are likely to inform management in the near future.

Keywords: cabozantinib; clear-cell renal cell carcinoma; immune checkpoint inhibitor; immunotherapy; ipilimumab; nivolumab; pembrolizumab; tyrosine kinase inhibitor.

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Conflict of interest statement

B.N. has acted as a paid member of the advisory board of Exelis and a paid participant in a case discussion for IntrinsiQ Specialty Solutions—AmerisourceBergen. M.A.B. has acted as a paid consultant for and/or as a member of the advisory boards of Exelixis, Bayer, BMS, Eisai, Pfizer, AstraZeneca, Janssen, Calithera Biosciences, Genomic Health, Nektar, EMD Serono, SeaGen, and Sanofi and has received grants to his institution from Merck, Xencor, Bayer, Bristol-Myers Squibb, Genentech/Roche, SeaGen, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Genome & Company, AAA, Peloton Therapeutics, and Pfizer for work performed as outside of the current study. All other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Current and novel therapies for mccRCC and their respective molecular targets. Created using Biorender®.
See this image and copyright information in PMC

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