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

Abstract

Abstract Background 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. Methods 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. Results 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). Conclusion The use of ARBs with PPAR‐γ‐activating property is linked with better survival among patients receiving ICIs.

Keywords

• angiotensin receptor blockers
• immune checkpoint inhibitors
• peroxisome proliferator‐activated receptor‐γ
• renin‐angiotensin‐aldosterone system inhibitors