Pirfenidone reduces lung cancer incidence by 73% in IPF patients with a pooled risk ratio of 0.39Antifibrotic drugs may lower lung cancer risk in patients with idiopathic pulmonary fibrosis

This systematic review and meta-analysis examined the association between antifibrotic therapies and lung cancer incidence in patients with idiopathic pulmonary fibrosis. The study population comprised 15582 patients receiving either pirfenidone or nintedanib. The setting was not reported, and the comparator group consisted of untreated controls. The analysis focused on lung cancer incidence as the primary outcome, with secondary outcomes not reported in the available data. The study design was observational, which limits the ability to infer causality. Geographic restriction to East Asian populations further constrains the generalizability of these findings. Biological heterogeneity exists between mechanistically distinct antifibrotic agents, and insufficient data were available for nintedanib specifically. Funding or conflicts of interest were not reported. The certainty of the evidence was not reported, and practice relevance was not reported. Causal claims for nintedanib must be avoided due to data insufficiency. Generalizability beyond East Asian populations is limited. Mechanism of cancer protection beyond antifibrotic actions remains unclear. Safety and tolerability findings were not reported, including adverse events, serious adverse events, discontinuations, or overall tolerability. Follow-up duration was not reported. The pooled risk ratio for lung cancer incidence was 0.39 with a 95% CI of 0.13-1.14. Pirfenidone-specific analysis showed a risk reduction of 73% with an RR of 0.27 and a 95% CI of 0.16-0.48. A sensitivity analysis for pirfenidone showed a risk reduction of 76% with an RR of 0.24 and a 95% CI of 0.08-0.69. Absolute numbers were not reported for any outcome. P-values were not reported individually, but confidence intervals provided the range of effect. The direction of the effect indicated risk reduction for pirfenidone. Observational designs introduce potential biases that cannot be fully controlled. Geographic restriction to East Asian populations may reflect regional differences in disease prevalence or treatment patterns. Biological heterogeneity between agents complicates direct comparison. Insufficient data for nintedanib prevents drawing conclusions for that specific drug. Safety profiles remain unknown as adverse events were not reported. Clinical implications suggest a potential signal for pirfenidone but require cautious interpretation. Questions remain unanswered regarding long-term safety and applicability to Western populations. The evidence is limited by observational designs, which precludes definitive causal statements. Future research should address these gaps with prospective, randomized data.