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

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.

Readily available drugs and other interventions to potentially improve the efficacy of immune checkpoint blockade in cancer

“…Additionally, it has been found that some ARBs are peroxisome proliferator-activated receptor- γ (PPAR- γ) and increase PD-1 blockade as well as cytotoxic T lymphocyte‐mediated antitumor activity ( 50 , 51 ). A retrospective study (n=167) was conducted to assess the impact of combining PPAR- γ activating ARBs and PD-1 blockade on survival of patients with different types of cancer was conducted ( 52 ). Compared to patients who were only treated with PD-1 blockade, patients who also received PPAR- γ activating ARBs showed both improved progression free survival and overall survival and had about a 50% reduction in mortality rates and disease progression.…”