Risk of interstitial lung disease associated with EGFR-TKIs in advanced non-small-cell lung cancer: a meta-analysis of 24 phase III clinical trials

Purpose: To assess the risk of interstitial lung disease (ILD) with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) gefitinib, erlotinib, and afatinib. Method: PubMed databases were searched for relevant articles. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR), and 95% confidence intervals (CIs) by using either random-effects or fixed-effect models. Results: The incidence of all-grade and high-grade (>= grade 3) ILD associated with EGFR-TKIs was 1.6% (95% CI, 1.0-2.4%) and 0.9% (95% CI, 0.6%-1.4%), with a mortality of 13.0% (95% CI, 7.6-21.6%). Patients treated with EGFR-TKIs had a significantly increased risk of developing all-grade (OR, 1.74; 95% CI, 1.25-2.43; P=0.001) and high-grade (OR, 4.38; 95% CI, 2.18-8.79; P<0.001) ILD. No significant difference in the risk of ILD was found in sub-group analysis according to EGFR-TKIs, percentage of EGFR mutation, study location, EGFR-TKIs-based regimens, and controlled therapy. Conclusions: Treatment with EGFR-TKIs is associated with a significantly increased risk of developing ILD.