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.
OBJECTIVE
To assess the risk of interstitial lung disease (ILD) with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) gefitinib, erlotinib, and afatinib.


METHODS
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.
Wei-Xiang
WX
Qi
Yuan-Jue
YJ
Sun
Zan
Z
Shen
Yang
Y
Yao
D000077716:Afatinib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000139:chemically induced*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011799:Quinazolines / Q000009:adverse effects; D012307:Risk Factors
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib
Afatinib,; Erlotinib,; Gefitinib,; Interstitial lung disease,; Meta-analysis; Non-small-cell lung cancer,