Role of Pirfenidone in the Primary Prophylaxis of Lung Cancer in Idiopathic Pulmonary Fibrosis Patients: A Systematic Review and Meta-Analysis. Publisher



Khan SJ ; Jaffari SMIA ; Basharat A ; Kasaeian A ; Shahzad M ; Jaglal MV
Source: Journal of Clinical Oncology Published:2025

Abstract

e22514Background: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease associated with a significantly increased risk of developing lung cancer. Pirfenidone, an anti-fibrotic agent commonly used for IPF, has been hypothesized to reduce lung cancer incidence by modulating fibrotic pathways linked to carcinogenesis. This systematic review evaluates the efficacy of pirfenidone in primary lung cancer prophylaxis in IPF patients. Methods: A systematic literature search was conducted on PubMed, Scopus, Google Scholar, and clinicalTrials.gov. Five retrospective studies reporting role of pirfenidone in primary prophylaxis of lung cancer in IPF patients were included. Key outcomes assessed were lung cancer incidence and hazard ratios (HR) between pirfenidone versus non-pirfenidone groups. Secondary outcomes included patient demographics, follow-up durations, and adverse effects. A random effect model using R was used to pool HR. Results: A total of 4529 (24%) out of 18, 601 patients who received pirfenidone were included for analysis. The median age of participants was 71 (67-73) years and 74% were male. The median follow-up was 3.8 years. The cumulative lung cancer incidence across all studies was significantly lower in the pirfenidone group 587 (3.16%) compared to the non-pirfenidone group 2474 (13.3%). However, one study reported a higher lung cancer incidence in the pirfenidone group (2.44 per 100 person-years) compared to the non-pirfenidone group (1.56 per 100 person-years). Despite this variation, the pooled hazard ratio (HR) demonstrated a protective effect of pirfenidone, with a HR of 0.331 (95% CI: 0.148–0.514 P = 0.01; I² = 73.7%). No significant pirfenidone safety concerns were consistently reported across the studies. The common causes of death among IPF patients included acute exacerbation, respiratory failure, and infection. Conclusions: This systematic review and meta-analysis highlight the potential of pirfenidone as a primary prophylactic agent for lung cancer, demonstrating significant reductions in lung cancer incidence and risk. While findings are promising, further prospective studies are warranted to confirm these results, elucidate mechanisms, and establish optimal dosing regimens. © 2025