1902P Association of High-Intensity Statins with Clinical Outcome in Malignant Pleural Mesothelioma and Advanced Non-Small Cell Lung Cancer Patients Treated with PD1 Inhibitors

Since a synergistic activity between statins and programmed death 1 (PD1) inhibitors has been documented in pre-clinical models, we investigated the impact of both high-intensity and low/moderate-intensity statin treatment on clinical outcome in thoracic cancer patients (pts) treated with PD1 inhibitors. Malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC) pts treated with PD1 inhibitors after progression to standard chemotherapy were examined at two European academic institutions. Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were analysed according to the use, type, lipophilicity and intensity of statins. Intensity of statins was defined according to the 2018 American College of Cardiology/American Heart Association Guideline on the Management of Blood Cholesterol. A total of 253 pts were examined. Twenty-seven out of 80 (34%) MPM and 40 out of 173 (20%) NSCLC pts were taking statins at start of PD1 inhibitors. In the whole cohort, statin use (regardless of intensity) was associated with increased ORR (32% versus 18%, P = 0.02), better PFS (median 6.7 versus 2.9 months, hazard ratio [HR] 0.57, 95% CI 0.39–0.83, P < 0.01), and better OS (median 13.1 versus 8.7 months, HR 0.67, 95% CI 0.45–1.00, P = 0.05). Use of high-intensity statins compared to no use was associated with increased ORR (46% versus 18%, P = 0.05), better PFS (median not reached versus 3.0 months, HR 0.33, 95% CI 0.15–0.75, P < 0.01), and better OS (median not reached versus 9.1 months, HR 0.20, 95% CI 0.05–0.84, P = 0.02). The same benefit was not observed for pts receiving low/moderate-intensity statins. Comparing them with no users, we found no differences in terms of ORR (P = 0.14) and OS (P = 0.33) and only a trend towards better PFS (P = 0.06). No difference in terms of PFS and OS was found according to the type and lipophilicity of statins. Statin use is associated with better outcome in MPM and NSCLC pts treated with PD1 inhibitors, in an intensity-dependent manner; prospective randomized studies are needed to further investigate this synergism.