Drug-specific timing and fatality patterns of EGFR-TKI-associated interstitial lung disease in NSCLC-related JADER...

Interstitial lung disease (ILD) is a toxicity of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). We characterized agent-specific fatality and timing patterns in the Japanese Adverse Drug Event Report database (JADER). We analyzed March 2026 JADER reports accepted from 2004 Q4 through 2025 Q2. Eligible reports involved single-agent osimertinib, gefitinib, erlotinib, or afatinib as the suspected drug for non-small cell lung cancer-related indications and were coded with the core ILD term. Fatal outcome, time to onset (TTO), and operationally defined pre-existing lung disease were evaluated. Logistic regression adjusted for agent, pre-existing lung disease, sex, age group, and report year. Among 3206 reports, fatal outcomes were reported in 10.8% of osimertinib, 33.1% of gefitinib, 32.2% of erlotinib, and 21.0% of afatinib cases. Among 2534 reports with evaluable TTO, median TTO were 55, 28, 22, and 35.5 days, respectively. Compared with osimertinib, adjusted odds of fatal outcome were higher for gefitinib (odds ratio (OR) 2.64, 95% confidence interval (CI) 1.80-3.86), erlotinib (OR 2.66, 95% CI 1.88-3.76), and afatinib (OR 1.87, 95% CI 1.22-2.88). Pre-existing lung disease showed an imprecise association (OR 1.30, 95% CI 1.00-1.70). ILD reports showed apparent agent-specific differences in timing and fatality. Osimertinib showed a later, less fatal pattern; gefitinib and erlotinib earlier, more fatal patterns; and afatinib an intermediate profile. These findings describe pharmacovigilance reporting patterns, not incidence, causal comparative safety, or treatment-selection guidance.