Background: Concomitant use of statins has been associated with improved survival outcomes in patients treated with immune checkpoint inhibitors (ICIs), but it is unclear if the timing of statin initiation plays a role in patient outcomes. We aimed to investigate the outcomes of patients who were started on a statin before and after initiation of ICI therapy. Methods: We performed a retrospective cohort study at two tertiary referral centers in Taiwan. We collected data on statin use including the timing of statin initiation, basic demographics, underlying comorbidities, and cancer information. We compared the overall survival (OS) and progression-free survival (PFS) between statin and non-statin users using Cox proportional hazard model analysis and Kaplan-Meier Survival analysis. Results: Among 734 patients who received ICIs, 76 patients received statins after ICI initiation, 52 patients received statins before ICI initiation, and 606 were non-statin users. Patients who received statins after ICI had a longer OS (median 37.6 vs. 11.3 vs. 10.3 months, p = 0.01) and PFS (median 10.5 vs. 5.6 vs. 6.3 months, p = 0.02) than patients who received statins before ICI and non-statin users. In Cox proportional hazard analyses, the use of statins after ICI was associated with a lower risk of mortality (HR, 0.65 [95% CI: 0.45-0.94], p = 0.02) or disease progression (HR, 0.71 [95% CI: 0.53-0.95], p = 0.02) compared with non-statin users. On the other hand, the use of statins before ICI was not associated with a lower risk of mortality (HR, 1.46 [95% CI: 0.96-2.22], p = 0.08) or disease progression (HR, 1.22 [95% CI: 0.86-1.73], p = 0.26) compared with non-statin users. These trends were observed in multivariate Cox proportional analyses adjusting for underlying comorbidities, cancer stage, type, and therapy. Conclusions: The use of statins after the initiation of immunotherapy is associated with improved survival outcomes.

^a Adjusted for the following covariates: age, sex, Eastern Cooperative Oncology Group Performance Status, cancer stage, cancer type, hypertension, diabetes, hyperlipidemia, chronic obstructive pulmonary disease, ischemic heart disease, stroke, heart failure, surgery, class of immune checkpoint inhibitors, platinum, tyrosine kinase inhibitors, anthracyclines, vascular endothelial growth factor inhibitors, and antimetabolites.