Background: In preclinical models, statins showed vaccine adjuvant activities and synergized with PD-1 inhibitors. We analyzed the impact of statin treatment on clinical outcome in thoracic cancer patients treated with PD-1 inhibitors. Methods: A total of 82 malignant pleural mesothelioma (MPM) and 179 advanced non-small cell lung cancer (aNSCLC) patients treated with PD-1 inhibitors as second or further line treatment were examined. Seventy-seven MPM patients treated with standard chemotherapy were analyzed as control cohort. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were calculated. Results: Among 253 patients with available data, statin use was associated with increased ORR (32% versus 18%, P =.02), PFS (median 6.7 versus 2.9 months, hazard ratio [HR] 0.57, 95% CI 0.39–0.83, P <.01), and OS (median 13.1 versus 8.7 months, HR 0.67, 95% CI 0.45–1.00, P =.05). In the control MPM cohort treated with chemotherapy (n = 77), no association was found. MPM patients who used statins showed improved ORR (22% versus 6%, P =.05), PFS (median 6.7 versus 2.4 months, P <.01), and OS (median not reached versus 6.0 months, P =.01). In aNSCLC patients, statin use was associated with improved ORR (40% versus 22%, P =.04) and PFS (median 7.8 versus 3.6 months, P =.03), but no significant difference in OS was found (median 13.1 versus 10.1 months, P =.30). Multivariable analysis confirmed the correlation between statin use and better PFS and OS in MPM and better PFS in aNSCLC. In the whole cohort, high but not low/moderate-intensity statins were associated with better OS compared to no user (P =.02 and P =.59, respectively). Conclusions: Our study showed that statins are associated with better clinical outcome in MPM and aNSCLC patients treated with PD-1 inhibitors in an intensity-dependent manner.

Immunotherapy, Lung cancer, Mesothelioma, Nivolumab, Pembrolizumab, Statin,
European Journal of Cancer
Erasmus MC Cancer Institute

Cantini, L, Pecci, F. (Federica), Hurkmans, D.P, Belderbos, R.A, Lanese, A. (Andrea), Copparoni, C. (Cecilia), … Berardi, R. (Rossana). (2021). High-intensity statins are associated with improved clinical activity of PD-1 inhibitors in malignant pleural mesothelioma and advanced non-small cell lung cancer patients. European Journal of Cancer, 144, 41–48. doi:10.1016/j.ejca.2020.10.031