Efficacy of Lipophilic Statins on Outcomes of Patients Treated with Immune Checkpoint Inhibitors

Abstract

<b><i>Background:</i></b> Statins are associated with improved survival outcomes in patients receiving immune checkpoint inhibitors (ICIs), but the impact of lipophilic and hydrophilic statin properties on patient outcomes is unknown. <b><i>Objectives:</i></b> We aim to investigate if statins with lipophilic properties are associated with clinical outcomes in patients receiving ICIs. <b><i>Method:</i></b> We conducted a retrospective cohort study at two tertiary referral centers in Taiwan comprising patients receiving ICIs between January 2015 and December 2021. We compared the comparative effect of lipophilic and hydrophilic statins on patient outcomes. The primary outcome was overall survival (OS) and the secondary outcome was progression-free survival (PFS). <b><i>Results:</i></b> Among 734 patients receiving ICIs, there were 51 lipophilic statin users, 25 hydrophilic statin users, and 658 nonusers. Lipophilic statin users had a longer median OS (38.0 [IQR, 16.7–not reached] vs. 15.2 [IQR, 8.2–not reached] months vs. 18.9 [IQR, 5.4 51.6] months) and PFS (13.0 [IQR, 4.7–41.5] vs. 8.2 [IQR, 2.2–14.7] months vs. 5.6 [2.3–18.7] months) than hydrophilic statin users and non-statin users. In Cox proportional hazard analyses, the use of lipophilic statins was associated with a 40–50% lower risk of mortality and disease progression compared with hydrophilic statin or non-statin users. <b><i>Conclusions:</i></b> The use of lipophilic statins seems to be associated with survival benefits in patients undergoing immunotherapy.