The impact of peroxisome proliferator-activated receptor-γ activating angiotensin receptor blocker on outcomes of patients receiving immunotherapy.

Abstract

Certain angiotensin receptor blockers (ARBs) have peroxisome proliferator-activated receptor-γ (PPAR-γ) activation property, which has been associated with improved programmed cell death ligand 1 blockade and cytotoxic T lymphocyte-mediated antitumor activity. We conducted a retrospective cohort study to investigate the impact of PPAR-γ-activating ARBs on patient survival in patients treated with immune checkpoint inhibitors (ICIs) across all types of cancers. A total of 167 patients receiving both angiotensin receptor blockers (ARBs) and immune checkpoint inhibitors (ICIs) were included. Compared with non-PPAR-γ-ARB users (n= 102), PPAR-γ-ARB users (n= 65) had a longer median overall survival (not reached [IQR, 16.0-not reached] vs. 18.6 [IQR, 6.1-38.6] months) and progression-free survival (17.3 [IQR, 5.1-not reached] vs. 8.2 [IQR, 2.4-18.6] months). In Cox regression analysis, the use of PPAR-γ-activating ARBs had an approximately 50% reduction in all-cause mortality and disease progression. Patients who received PPAR-γ-activating ARBs also had higher clinical benefit rates than non-PPAR-γ-ARB users (82% vs. 61%, p= 0.005). The use of ARBs with PPAR-γ-activating property is linked with better survival among patients receiving ICIs.