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Serzan et al. J Cancer Metastasis Treat 2021;7:39 Journal of Cancer
DOI: 10.20517/2394-4722.2021.76
Metastasis and Treatment

Review Open Access

Current and emerging therapies for first line
treatment of metastatic clear cell renal cell

carcinoma

Michael T. Serzan, Michael B. Atkins
Georgetown Lombardi Comprehensive Cancer Center, Washington, DC 20057, USA.
Correspondence to: Dr. Michael B. Atkins, Department of Oncology, Georgetown Lombardi Comprehensive Cancer Center,
3970 Reservoir Rd, NW Research Building, Room E501, Washington, DC 20057, USA. E-mail: mba41@georgetown.edu

How to cite this article: Serzan MT, Atkins MB. Current and emerging therapies for first line treatment of metastatic clear cell
renal cell carcinoma. J Cancer Metastasis Treat 2021;7:39. https://dx.doi.org/10.20517/2394-4722.2021.76

Received: 26 Mar 2021 Accepted: 12 May 2021 Available online: 12 Jul 2021
Academic Editor: Hendrik Paul Van Poppel Copy Editor: Yue-Yue Zhang Production Editor: Yue-Yue Zhang

Abstract
The therapeutic landscape for advanced clear cell renal cell carcinoma (ccRCC) is rapidly evolving with improved
knowledge of the biology of disease leading to the incorporation of a variety of antiangiogenic agents and
immunotherapies. In this review, we discuss historical, current, and emerging first line treatment options for
patients with advanced ccRCC. These include data with single agent vascular endothelial growth factor receptor
tyrosine kinase inhibitors (TKIs): sunitinib, pazopanib and cabozantinib as well as the recently reported results for
the combination of lenvatinib and everolimus (mTOR inhibitor). We also discuss results of the nivolumab anti-
programmed cell death (PD-1)/ipilimumab (anti-cytotoxic T lymphocyte-associated antigen 4) combination as
well as emerging front-line data with nivolumab and pembrolizumab (anti-PD-1) monotherapy. Finally, we review
data supporting recent approvals of TKI and anti-PD-1 or anti-PD-Ligand 1 (PD-L1) combinations (e.g.,
axitinib/pembrolizumab, axitinib/avelumab and cabozantinib/nivolumab) and initial outcomes of lenvatinib
(multi-kinase inhibitor) and pembrolizumab. With many individual and combination treatment options and the lack
of head-to-head comparisons, treatment selection will depend on the goals of therapy (endpoints) and the
identification and validation of clinical and tumor-based predictive biomarkers that are linked to the desired
treatment endpoints.

Keywords: Renal cell carcinoma, nivolumab, ipilimumab, axitinib, pembrolizumab, avelumab, biomarkers

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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