Impact of antifibrotic therapy on lung cancer incidence and mortality in patients with idiopathic pulmonary fibrosis

Background: Patients with idiopathic pulmonary fibrosis (IPF) are at risk of lung cancer development. Antifibrotic therapy could slow disease progression of IPF, but there is limited data on its effectiveness on lung cancer. Here, we aimed to investigate lung cancer incidence and the risk of mortality of patients with IPF receiving antifibrotic therapy.

Methods: Data from the Korean National Health Insurance service database between October 2015 and September 2021 were used. The incidence of lung cancer and all-cause mortality in the IPF cohort was analyzed depending on pirfenidone treatment. Those who were diagnosed with lung cancer prior to IPF diagnosis were excluded.

Results: Among the 5,038 patients with IPF who were eligible for the study, pirfenidone was administered to 880 patients. Median follow-up duration was 4,872.8 and 23,612.1 person-years in the groups receiving and not receiving pirfenidone, respectively. The incidence of lung cancer was significantly higher in the pirfenidone group compared to non-users [2.44 vs. 1.56 per 100 person-years; risk ratio 1.56; 95% confidence interval (CI), 1.27-1.92]. However, the risk of mortality did not differ significantly between patients receiving pirfenidone and those who did not. Further analysis was conducted to assess lung cancer development and pirfenidone therapy. Among patients with lung cancer, those treated with pirfenidone demonstrated significantly improved survival compared to those not receiving pirfenidone therapy (log-rank test, P<0.001). Pirfenidone therapy was associated with a protective effect on mortality in IPF patients with lung cancer [hazard ratio, 0.61; 95% CI, 0.43-0.85].

Conclusions: Antifibrotic therapy was associated with improved survival in patients with IPF who develop lung cancer, even though the incidence of lung cancer was higher in those receiving antifibrotic treatment compared to those do not.