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

Abstract

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.

Keywords:

• Non-small-cell lung cancer
• Interstitial lung disease
• Erlotinib
• Gefitinib
• Afatinib
• Meta-analysis