Effect of statins on outcomes in renal cell carcinoma patients undergoing immune checkpoint inhibitor therapy: A retrospective US cohort study.

Abstract

e16553 Background: Immune checkpoint inhibitors (ICI) have transformed the treatment of renal cell carcinoma (RCC). Statins possess pleiotropic anti-tumor effects, including anti-inflammatory and immunomodulatory properties that may influence ICI efficacy and toxicity. However, real-world data evaluating their impact on outcomes in RCC are limited. Methods: We conducted a retrospective cohort study using the TriNetX database, including adults (≥18 years) with RCC treated with ICIs. Patients were categorized by statin exposure during ICI therapy. Cohorts were 1:1 propensity score–matched (PSM) for age, sex, race, comorbidities, and concomitant medications. Outcomes over a 3-year follow-up period included overall mortality, immune-related adverse events (irAEs), and major adverse cardiovascular events (MACE). Cox proportional hazards models and Kaplan–Meier survival analyses were performed. Results: A total of 6,162 patients without statin exposure and 4,633 with statin exposure met eligibility criteria. After 1:1 PSM, 2,787 patients were included in each cohort. Baseline characteristics were statistically similar (p > 0.05) (Table 1). After a 3-year follow-up period, statin use was associated with significantly increased survival (63.1% vs. 49%; p < 0.01). There was decreased risk of mortality in this cohort (28% vs. 36%; hazard ratio [HR] = 0.63, 95% CI 0.57-0.69). Median overall survival was not reached in the statin cohort compared with 1,074 days in the non-statin cohort. Statin exposure increased the risk of select irAEs such as colitis/enteritis (10.9% vs 6.0%; HR = 1.58, 95% CI 1.31–1.90), rash (12.5% vs 8.9%; HR = 1.23, 95% CI 1.04–1.44), and thyroiditis/hypophysitis/adrenal insufficiency (9.9% vs 6.9%; HR = 1.27, 95% CI 1.05–1.52). MACE occurred more frequently among statin users (32.2% vs 18.9%; HR = 1.58, 95% CI 1.42–1.76). No significant differences were observed for immune-mediated hepatitis, pneumonitis, or diabetes mellitus. Conclusions: In this large, real-world study of RCC patients on ICIs, statin use was associated with improved overall survival but was associated with higher risks of select irAEs and MACE. Further prospective studies are needed to validate causality and identify patients most likely to derive net benefit from concomitant statin therapy during ICI treatment. Baseline characteristics of the two cohorts after propensity score–matching. Characteristic RCC without Statins(N = 2,787) RCC with Statins(N = 2,787) P value Age at index [mean ± SD (years)] 65.3 ± 10.7 65.2 ± 9.8 0.681 Sex   Female, n (%) 787 (28.2) 818 (29.4) 0.359   Male, n (%) 2,000 (71.8) 1,969 (70.6) 0.359 Race   White, n (%) 2,168 (77.8) 2,156 (77.4) 0.700   Hispanic, n (%) 219 (7.9) 220 (7.9) 0.960   Black or African American, n (%) 171 (6.1) 166 (6.0) 0.779