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Review
. 2019 Jun;17(3):e513-e521.
doi: 10.1016/j.clgc.2019.01.017. Epub 2019 Feb 5.

Immunotherapy Is Changing First-Line Treatment of Metastatic Renal-Cell Carcinoma

Matthew K Labriola  1 , Kristen A Batich  1 , Jason Zhu  1 , Megan A McNamara  1 , Michael R Harrison  1 , Andrew J Armstrong  1 , Daniel J George  1 , Tian Zhang  2
Affiliations
Review

Immunotherapy Is Changing First-Line Treatment of Metastatic Renal-Cell Carcinoma

Matthew K Labriola et al. Clin Genitourin Cancer. 2019 Jun.

Abstract

The incidence of renal-cell carcinoma has been increasing each year, with nearly one third of new cases diagnosed at advanced or metastatic stage. The advent of targeted therapies for metastatic renal-cell carcinoma (mRCC) has underscored the need to subtype tumors according to tumor-immune expression profiles that may more reliably predict treatment outcomes. Over the past 2 decades, several vascular endothelial growth factor (VEGF) and tyrosine kinase inhibitors have been the mainstay for first- and second-line treatment of mRCC. Very recently, immunotherapy checkpoint inhibitors have significantly changed the treatment landscape for patients with mRCC, particularly for first-line treatment of intermediate to poor risk mRCC patients. Now, combination immunotherapy as well as combinations of immunotherapy with targeted agents can significantly alter disease outcomes. The field of immuno-oncology for mRCC has unveiled a deeper understanding of the immunoreactivity inherent to these tumors, and as a result combination therapy is evolving as a first-line modality. This review provides a timeline of advances and controversies in first-line treatment of mRCC, describes recent advances in understanding the immunoreactivity of these tumors, and addresses the future of combination anti-VEGF and immunotherapeutic platforms.

Keywords: Immune checkpoint inhibitors; Metastatic renal-cell carcioma; Targeted therapies; VEGF therapies; VEGF-immunotherapy combinations.

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Conflict of interest statement

Disclosure

A.J.A. has received funding (to Duke) from Medivation/Astellas, Bayer, Dendreon, Janssen, Active Biotech, Sanofi-Aventis, Gilead, Novartis, and Pfizer; consulting/speaking with Dendreon and Sanofi Aventis; and consulting with Medivation/Astellas and Janssen. D.J.G. has received research funding (to Duke) from Acerta, Astellas, Bayer, Bristol-Myers Squibb, Dendreon, Exelixis, Innocrin, Janssen, Novartis, Pfizer; consulting and speaking with Bayer, Exelixis, Sanofi; and consulting with Astellas, AstraZeneca, Bristol-Myers Squibb, Innocrin, Janssen, Merck, Myovant, Pfizer. T.Z. has received research funding (to Duke) from Pfizer, Janssen, Acerta, Abbvie, Novartis, Merrimack, OmniSeq, PGDx, and Merck; consulting/speaking with Genentech Roche and Exelixis; consulting with AstraZeneca, Amgen, Pharmacyclics, BMS, Pfizer, Foundation Medicine, Janssen, Bayer, and Sanofi Aventis; and stock ownership/employment (spouse) from Capio Biosciences. M.M. has received research funding (to Duke) from Janssen, Agensys, Bayer, Seattle Genetics, and Clovis. The other authors have stated that they have no conflict of interest.

Figures

Figure 1
Figure 1. US Food and Drug Administration Approval Timeline of Treatment Options for Metastatic Renal-Cell Carcinoma Therapy
Figure 2
Figure 2. VEGF Modulation of Function of T Cells, Suppressive Immune Cells, and Stroma in Tumor Microenvironment. Dotted Gray Lines Indicate Differentiation From iMC to TAM and iDC, Respectively
Abbreviations: iDC = immature dendritic cell; iMC = immature myeloid cell; matDC = mature dendritic cell; MDSC = myeloid-derived suppressor cell; TAM = tumor-associated macrophage; T-reg = T-regulatory cell. Data from Ott PA, Hodi FS, Buchbinder EI. Inhibition of immune checkpoints and vascular endothelial growth factor as combination therapy for metastatic melanoma: an overview of rationale, preclinical evidence, and initial clinical data. Front Oncol 2015; 5:202.
See this image and copyright information in PMC

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