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

• Published in: Cancer medicine (Malden, MA) MA), 2023-04, Vol.12 (8), p.9583-9588
• Main Authors: Chiang, Cho‐Han, Chang, Yu‐Cheng, Wang, Shih‐Syuan, Chen, Yuan‐Jen, See, Xin Ya, Peng, Chun‐Yu, Hsia, Yuan Ping, Chiang, Cho‐Hsien, Chiang, Cho‐Hung, Peng, Cheng‐Ming
• Format: Article
• Language: English
• Subjects: Angiotensin; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Angiotensin Receptor Antagonists - therapeutic use; angiotensin receptor blockers; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antitumor activity; Apoptosis; Brief Communication; Cancer therapies; Cardiac arrhythmia; Cardiovascular disease; Cell death; Cohort analysis; Cytotoxicity; Diabetes; Endocrine system; Heart failure; Humans; Hyperlipidemia; Hypertension; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - pharmacology; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Kidney diseases; Kinases; Ligands; Liver cancer; Lung cancer; Lymphocytes T; Mortality; Patients; Peroxisome proliferator-activated receptors; peroxisome proliferator‐activated receptor‐γ; PPAR gamma - metabolism; Regression analysis; Remission (Medicine); renin‐angiotensin‐aldosterone system inhibitors; Retrospective Studies
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.5734

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.