Statin use and prognosis of lung cancer: a systematic review and meta-analysis of observational studies and randomized controlled trials

Abstract

Background: Previous clinical studies reported inconsistent results on the associations of statins with the mortality and survival of lung cancer patients. This review and meta-analysis summarized the impact of statins on mortality and survival of lung cancer patients.

Materials and methods: Eligible papers of this meta-analysis were searched by using PubMed, EMBASE, and Cochrane until July 2017. Primary end points were the mortality (all-cause mortality and cancer-specific mortality) and survival (progression-free survival and overall survival) of patients with statin use. Secondary end points were overall response rate and safety. The random-effects model was used to calculate pooled HRs and 95% CIs.

Results: Seventeen studies involving 98,445 patients were included in the meta-analysis. In observational studies, the pooled HR indicated that statins potentially decreased the cancer-specific mortality and promoted the overall survival of lung cancer patients. Statins showed an association with decreased all-cause mortality in cohort studies (HR =0.77, 95% CI: 0.59-0.99), but not in case-control studies (HR =0.75, 95% CI: 0.50-1.10). However, statin use showed no impact on mortality and overall survival in randomized controlled trials. Meanwhile, this meta-analysis indicated that statin use did not affect the progression-free survival of lung cancer patients in observational studies and randomized controlled trials. In addition, statins potentially enhanced the effects of tyrosine kinase inhibitors (HR=0.86, 95% CI: 0.76-0.98) and chemotherapy (HR=0.86, 95% CI: 0.81-0.91) on the overall survival of patients with non-small-cell lung cancer, but did not increase overall response rate and toxicity.

Conclusion: Statins were potentially associated with the decreasing risk of mortality and the improvement of overall survival in observational studies but not in randomized controlled trials.

Keywords: lung cancer; mortality; prognosis; statin; statins; survival.

Figure 1

Flow diagram of the selection of publications included in the meta-analysis.

Figure 2

Forest plot: overall meta-analysis of mortality and survival between statin use and lung cancer. Notes: (A) all-cause mortality; (B) cancer-specific mortality; (C) progression-free survival; and (D) overall survival. Weights are from random-effects analysis. Abbreviation: Cc, case-control.

Figure 2

Forest plot: overall meta-analysis of mortality and survival between statin use and lung cancer. Notes: (A) all-cause mortality; (B) cancer-specific mortality; (C) progression-free survival; and (D) overall survival. Weights are from random-effects analysis. Abbreviation: Cc, case-control.

Figure 3

Funnel plot for publication bias of mortality and survival between statin use and lung cancer. Note: (A) all cause mortality (Egger’s test =0.848 and Begg’s test =0.548); (B) cancer-specific mortality (Egger’s test =0.082 and Begg’s test =0.035); (C) progression-free survival (Egger’s test =0.431 and Begg’s test =0.133); and (D) overall survival (Egger’s test =0.425 and Begg’s test =0.732).