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Review
. 2020 Mar 18:12:1758835920907504.
doi: 10.1177/1758835920907504. eCollection 2020.

Tyrosine kinase inhibitors and immunotherapy combinations in renal cell carcinoma

Elie Rassy  1 , Ronan Flippot  1 , Laurence Albiges  2
Affiliations
Review

Tyrosine kinase inhibitors and immunotherapy combinations in renal cell carcinoma

Elie Rassy et al. Ther Adv Med Oncol. .

Abstract

The treatment landscape of metastatic renal cell carcinoma (mRCC) has been transformed with the advent of antiangiogenics, notably tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor receptor (VEGFR), and immune checkpoint inhibitors (ICIs). Both treatment options have improved outcomes of patients and modified the natural history of mRCC. Clinical investigations have focused on evaluating combination regimens containing ICIs and VEGFR-directed TKIs. Namely, the combinations of axitinib plus pembrolizumab (KEYNOTE-426) and axitinib plus avelumab (JAVELIN RENAL 101) have shown improved outcomes compared with sunitinib in treatment-naïve patients with mRCC. In this review, we discuss the clinical data of single-agent TKIs and ICIs in mRCC and the rationale for the combination ICIs and TKIs based on preclinical and clinical evidence. We also explore the current challenges for regimen selection and development of predictive biomarkers.

Keywords: angiogenesis; combination; immune checkpoint inhibitors; immunotherapy; renal cell carcinoma; tyrosine kinase inhibitors.

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Conflict of interest statement

Conflict of interest statement: Elie Rassy and Ronan Flippot: none Laurence Albiges: Consulting/advisory role: Novartis (Institution), Amgen (Institution), Bristol-Myers Squibb (Institution), Ipsen (Institution), Roche (Institution), Pfizer (Institution), Astellas Pharma (Institution), Merck (Institution), MSD (Institution), AstraZeneca (Institution), Exelixis (Institution), Corvus Pharmaceuticals (Institution), Peloton therapeutics (Institution). Research Funding: Bristol-Myers Squibb (Institution).

Figures

Figure 1.
Figure 1.
The interplay between the immune system and angiogenesis in renal cell carcinoma. HIF2α, hypoxia-inducible factor alpha; PD-1, programmed cell death protein; PD-L1, programmed cell death protein ligand; VEGF, vascular endothelial growth factor.
See this image and copyright information in PMC

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