Risk of interstitial lung disease with gefitinib and erlotinib in advanced non-small cell lung cancer: A systematic review and meta-analysis of clinical trials.

Abstract

e19149 Background: Gefitinib and erlotinib are oral EGFR-TKIs widely used in advanced NSCLC. The reported incidence and risk of interstitial lung disease (ILD) events associated with gefitinib and erlotinib varies widely and has been inconsistently reported in trials. Therefore, we performed a systematic review and meta-analysis to determine the incidence and the relative risk (RR) associated with the use of gefitinib and erlotinib. Methods: PubMed databases were searched for articles published from January 2000 to October 2012, and abstracts from ASCO and ESMO meetings (2000-2012) were searched for relevant studies. Eligible studies included randomized controlled trials with gefitinib and erlotinib in advanced NSCLC patients. Summary incidence rates, RRs, and 95% CIs were calculated using fixed-effects or random-effects models, depending on the heterogeneity of the included studies. Results: 15,618 patients from 29 randomized controlled trials were selected for this meta-analysis. The overall incidence for all-grade ILD events was 1.2% (95% CI, 0.9% to 1.6%) among patients receiving gefitinib and erlotinib, with a mortality of 22.8% (95% CI, 14.6% to 31.0%). The summary incidence of fatal ILD events was 0.2% (95% CI, 0.1% to 0.3%) in 26 trials with available data. Compared with controls, the RR of all-grade and fatal ILD events was 1.53 (95% CI, 1.13 to 2.08; P = 0.006) and 1.96 (95% CI, 1.03 to 3.72, P = 0.041), respectively. After stratifying patients by study location (Asian versus non-Asian), the RR of all-grade ILD events was 2.00 (95% CI, 1.23 to 3.25) and 1.30 (95% CI, 0.88 to 1.91) for Asian studies and non-Asian studies, respectively. The analysis was also stratified for drug type, trial phase, treatment line, and studies quality, but no significant differences in RRs were observed in all subgroup analyses. Conclusions: Treatment with EGFR-TKIs gefitinib and erlotinib is associated with a significant increase in the risk of developing both all-grade and fatal ILD events in advanced NSCLC.