Incidence and risk of infections associated with EGFR-TKIs in advanced non-small-cell lung cancer: a systematic review and meta-analysis of randomized controlled trials

Currently, the overall incidence and risk of infections with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients remained undetermined. We searched Pubmed for related articles published from 1 January 1990 to 31 November 2015. Eligible studies included prospective randomized controlled trials (RCTs) evaluating therapy with or without EGFR-TKIs in patients with NSCLC. Data on infections were extracted. Pooled incidence, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were calculated. A total of 17,420 patients from 25 RCTs were included. The use of EGFR-TKIs significantly increased the risk of developing all-grade infections (Peto OR 1.48, 95% CI: 1.12-1.96, p = 0.006) in NSCLC patients, but not for severe (Peto OR 1.26, 95% CI: 0.96-1.67, p = 0.098) and fatal infections (Peto OR 0.81, 95% CI: 0.43-1.53, p = 0.52). Meta-regression indicated the risk of infections tended to increase with the treatment duration of EGFR-TKIs. No publication of bias was detected. In conclusion, the use of EGFR-TKIs significantly increased the risk of developing all-grade infectious events in NSCLC patients, but not for severe and fatal infections. Clinicians should be aware of the risks of infections with the administration of these drugs in these patients.