Anti-angiogenic agents, such as
vascular endothelial growth factor (
VEGF) receptor tyrosine kinase inhibitors and anti-
VEGF antibodies, and
immune checkpoint inhibitors (CPIs) are standard treatments for advanced
renal cell carcinoma (aRCC). In the past, these agents were administered as sequential monotherapies. Recently, combinations of anti-angiogenic agents and CPIs have been approved for the treatment of aRCC, based on evidence that they provide superior efficacy when compared with
sunitinib monotherapy. Here we explore the possible mechanisms of action of these combinations, including a review of relevant preclinical data and clinical evidence in patients with aRCC. We also ask whether the benefit is additive or synergistic, and, thus, whether concomitant administration is preferred over sequential monotherapy. Further research is needed to understand how combinations of anti-angiogenic agents with CPIs compare with
CPI monotherapy or combination
therapy (e.g.,
nivolumab and
ipilimumab), and whether the long-term benefit observed in a subset of patients treated with
CPI combinations will also be realised in patients treated with an anti-angiogenic
therapy and a
CPI. Additional research is also needed to establish whether other elements of the tumour microenvironment also need to be targeted to optimise treatment efficacy, and to identify
biomarkers of response to inform personalised treatment using combination
therapies.