Statins use and prognosis in lung cancer patients treated with immune checkpoint inhibitors: evidence from a meta-analysis

Vollständiger Abstract

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Background Lung cancer remains one of the most common and lethal malignancies worldwide. The advent of immune checkpoint inhibitors (ICIs) has substantially improved survival outcomes in patients with advanced disease; nevertheless, a considerable proportion of patients exhibit suboptimal responses to ICI monotherapy. In recent years, statins have garnered attention for their potential immunomodulatory and anti-inflammatory properties. Preclinical evidence suggests that statins may enhance antitumor immune responses by modulating the tumor microenvironment and facilitating antigen presentation. However, existing clinical data remain inconclusive regarding whether statin use influences prognosis in lung cancer patients receiving ICIs. Accordingly, this meta-analysis was undertaken to evaluate the impact of statin use on survival outcomes in this patient population, with the aim of informing clinical decision-making regarding combination strategies. Methods We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science for clinical studies published from database inception to June 2026 that examined the association between statin use and outcomes in lung cancer patients treated with ICIs. Two investigators independently screened the literature, extracted data, and assessed the risk of bias using the Newcastle-Ottawa Scale (NOS). The primary endpoints were overall survival (OS) and progression-free survival (PFS). A meta-analysis was performed using Stata 15.0 software. Results Twelve studies comprising 5,156 participants were included. Pooled analysis demonstrated that statin use was associated with significantly improved OS (HR = 0.76, 95% CI (0.63, 0.91), P = 0.003) and PFS (HR = 0.82, 95% CI (0.69, 0.96), P = 0.017). Subgroup analyses revealed that the survival benefit remained significant for both OS and PFS in multivariate-adjusted estimates. In univariate analyses and in larger studies (n > 500), the benefits did not attain statistical significance. Geographically, statins significantly improved OS in non-Asian populations, whereas the PFS benefit in these populations did not reach significance. Conclusions This meta-analysis indicates that statin use is associated with significantly prolonged OS and PFS in lung cancer patients receiving ICIs, suggesting a potential role for statins in augmenting ICI efficacy. However, given that the included studies were predominantly retrospective observational designs, these findings should be interpreted with caution. Prospective, large-scale randomized controlled trials are warranted to confirm the survival benefits of combined statin and ICI therapy and to define the optimal timing and target population for such combination. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420261420311