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

Eur J Cancer. 2021 Feb;144:41-48. doi: 10.1016/j.ejca.2020.10.031. Epub 2020 Dec 14.


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.

Keywords: Immunotherapy; Lung cancer; Mesothelioma; Nivolumab; Pembrolizumab; Statin.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Mesothelioma, Malignant / drug therapy*
  • Mesothelioma, Malignant / pathology
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Response Evaluation Criteria in Solid Tumors*
  • Survival Rate


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor