Statin Use With Immune Checkpoint Inhibitors and Survival in Nonsmall Cell Lung Cancer

Abstract

Objective: To determine the association between concurrent statin use with immune checkpoint inhibitors (ICIs) and lung cancer-specific and overall mortality in patients with nonsmall cell lung cancer (NSCLC).

Materials and methods: SEER-Medicare was used to conduct a retrospective study of Medicare beneficiaries ≥65 years of age diagnosed with NSCLC between 2007 and 2017 treated with an ICI. Patients were followed from date of first ICI claim until death, 1 month from last ICI claim, or 12/31/2018, whichever came first. Associations for time-updated statin use and lung cancer-specific mortality, and overall mortality were estimated using Cox models adjusted for demographic, pathological, treatment-related factors, and a propensity score for statin use.

Results: Among 1,401 patients, concurrent statin use with any ICI was associated with 41% lower risk of lung-cancer specific mortality compared to patients receiving ICI not using a statin (HR = 0.59; 95% CI = 0.35-0.99). Statin use was associated with a similarly lower risk of overall mortality (HR = 0.62; 95% CI = 0.41-0.94). Consistent inverse associations were observed when restricting to PD-1 inhibitors and by statin type. Limited anti-PD-L1 treatment prevented analysis in this subgroup.

Conclusion: Concurrent statin use with ICIs was associated with lower risk of lung cancer-specific and overall mortality in a population-based sample of older patients with NSCLC. Future work is needed to confirm these findings in prospective studies and randomized trials, including evaluating concurrent statin use with frontline ICIs, deciphering the underlying mechanism, and determining the optimal statin-ICI combination that maximize clinical benefit.

Keywords: Mortality; Older adults; Retrospective cohort study; SEER-Medicare; Survival analysis.