| Abstract: |
Background: The cancer-anorexia-cachexia syndrome (CACS) is a common and debilitating wasting disorder characterized by loss of skeletal muscle and worse morbidity and mortality. In pre-clinical studies, CACS is associated with loss of peroxisome proliferator-activated receptor alpha (PPAR-α) dependent ketone production in the liver. Fibrates are PPAR-α agonists that are commonly used to treat dyslipidemia. Treating mice with fibrates was found to prevent skeletal muscle loss. We examine whether patients with cancer treated with PPAR-α agonists experience less CACS. Methods: We performed a retrospective cohort study of patients (N = 6922) at Memorial Sloan Kettering Cancer Center who were diagnosed with non-small cell lung cancer (NSCLC) between 2002 and 2017 and were incidentally prescribed fenofibrate or gemfibrozil at the time of diagnosis. These patients were compared to a propensity score-matched control set who were not taking either drug. The primary outcome included a composite outcome of CACS, which included significant weight loss before or after the time of diagnosis. Secondary outcomes included change in cross-sectional skeletal muscle area over time as measured in serial CT imaging studies and overall survival. Descriptive statistics, Kaplan–Meier analysis and multivariable logistic regression were performed to compare outcomes between the two groups. Results: Among patients with NSCLC, 149 were taking fenofibrate or gemfibrozil at the time of diagnosis. A 2:1 propensity score-matched cohort of 298 patients was created that was well-matched with regard to baseline characteristics. Regarding the primary composite outcome, there was no significant difference in the prevalence of CACS between those taking fibrates and propensity-matched controls (49.7 vs. 46.6%). When skeletal muscle mass was measured directly using cross-sectional imaging, patients on fibrates were found to have lost significantly less muscle area over time (−3.3 vs.−4.2%, p = 0.03). There was no difference in overall survival between groups. Conclusion: Patients with NSCLC taking fibrates at the time of diagnosis lost less muscle area over time. In a secondary analysis, this change was not associated with a change in overall survival, though this study was likely underpowered for this analysis. © 2025 Elsevier B.V., All rights reserved. |
