Abstract
BACKGROUND: Statin drugs, frequently used to treat hyperlipidemia, are associated with improved survival outcomes in multiple solid tumor types, including head and neck squamous cell carcinoma (HNSCC). Preclinical studies suggest that manipulation of cholesterol with statins and other agents can enhance the function of multiple components involved in anti-tumor immune responses. Retrospective studies in other solid tumor types suggest that statin therapy is associated with improved responses to immune checkpoint blockade (ICB), but this has not yet been investigated in HNSCC. METHODS: Pharmacy records were searched for patients with recurrent/metastatic HNSCC treated at our institution with pembrolizumab or nivolumab from 2015 to 2022. Patients who received less than 3 doses of ICB were excluded. Univariate and multivariate analyses were performed to determine the association between statin use and objective response, progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 158 patients were included. Statins were significantly associated with objective response; the strongest associations were seen with rosuvastatin and lovastatin. On multivariate analyses, statins were independently associated with objective response but not with PFS or OS. CONCLUSIONS: Statin therapy appears to be an independent predictor of response to ICB in HNSCC. Larger, prospective studies are needed to determine whether specific statin drugs can improve survival outcomes in ICB-treated patients.