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.

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 / Cantini, L.; Pecci, F.; Hurkmans, D. P.; Belderbos, R. A.; Lanese, A.; Copparoni, C.; Aerts, S.; Cornelissen, R.; Dumoulin, D. W.; Fiordoliva, I.; Rinaldi, S.; Aerts, J. G. J. V.; Berardi, R.. - In: EUROPEAN JOURNAL OF CANCER. - ISSN 0959-8049. - 144:(2021), pp. 41-48. [10.1016/j.ejca.2020.10.031]

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

Cantini L.;Berardi R.
2021-01-01

Abstract

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.
2021
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/287274
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