Risk of interstitial lung disease and other pulmonary related adverse events among patients taking EGFR inhibitors: A meta-analysis of randomized controlled trials.

Abstract

e19155 Background: Epidermal growth factor receptor (EGFR) inhibitors are suspected of being a potential cause of interstitial lung disease (ILD). This speculation is based largely on case reports and series in which it is difficult to establish causality. In this meta-analysis we evaluated randomized controlled trials (RCTs) involving EGFR inhibitors to verify if a relationship exists between exposure to EGFR inhibitors and development of ILD and other pulmonary-related events. Methods: EMBASE and Medline were searched for all RCTs evaluating cetuximab, gefitinib or erlotinib in non-small cell lung cancer (NSCLC). Studies were disqualified if the control contained any EGFR inhibitor or drug known to cause ILD. Thirty-one RCTs with 15,736 patients were identified. The primary outcome was ILD incidence. ILD is poorly defined and there is overlap with other pulmonary related outcomes including pneumonia, acute respiratory failure (ARF) and pneumonitis, and these were therefore secondary outcomes of interest. For all outcomes, a fixed-effects meta-analysis was performed. Results: For the primary outcome, there is a 173% increased risk of ILD among patients given EGFR inhibitors (RR 2.73, 95% CI: 1.74-4.23, p<0.001) across 15 RCTs that report on ILD incidence. Among secondary endpoints, there is an 86% increased risk of pneumonia (RR 1.86, 95% CI 1.36-2.53, p<0.001), a 19% increased risk of pneumonitis (RR 1.19, 95% CI: 0.62-2.27, p=0.59) and a 33% increased risk of ARF (RR 1.33, 95% CI: 0.65-2.72, p=0.44) among patients given EGFR inhibitors. There is minimal heterogeneity across trials for all above outcomes. Conclusions: EGFR inhibitors play a direct role in causing or contributing to ILD progression in patients with NSCLC who are susceptible to alveolar damage from prior chemoradiation therapy. Additionally, EGFR inhibitors seem to be associated with an increased risk for other pulmonary related events.This research suggests that caution should be undertaken in administering EGFR inhibitors to patients with poor baseline lung function or pre-existing pulmonary disease.