TY - JOUR
T1 - Combination of Anti-Angiogenics and Checkpoint Inhibitors for Renal Cell Carcinoma
T2 - Is the Whole Greater Than the Sum of Its Parts?
AU - Jonasch, Eric
AU - Atkins, Michael B.
AU - Chowdhury, Simon
AU - Mainwaring, Paul
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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.
AB - 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.
KW - Advanced renal cell carcinoma
KW - Combination therapy
KW - Immune checkpoint inhibitors
KW - Vascular endothelial growth factor
UR - http://www.scopus.com/inward/record.url?scp=85123358527&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85123358527&partnerID=8YFLogxK
U2 - 10.3390/cancers14030644
DO - 10.3390/cancers14030644
M3 - Review article
C2 - 35158916
AN - SCOPUS:85123358527
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 3
M1 - 644
ER -