Rash Rates with EGFR Inhibitors: Meta-Analysis

Introduction: Currently marketed epidermal growth factor receptor inhibitors (EGFRIS) have been associated with high rates of dermatologic toxicity. Methods: We formally reviewed the literature at MEDLINE and EMBASE. Additional searches were conducted using Internet search engines. Studies were eligible if they were randomized controlled clinical trials of egfris, specifically cetuximab and panitumumab, in which at least one arm consisted of a non-egfri treatment and rash safety data were reported. The random effects method was used to pool differences in incident rash rates. Results are summarized as differences in incident rash (EGFRIS therapy rate minus the non-EGFRIS therapy rate) with corresponding 95% confidence intervals (CIS) for all severity grades of rash and for grades 3 and 4 rash. Results: Sixteen studies met the initial inclusion criteria of randomized controlled trials comparing EGFRIS with non-EGFRIS therapy. Seven publications that provided information on all severity grades of rash were found to have an overall difference in incident rash rate of 0.74 (95% CI: 0.68 to 0.81; p < 0.01). Thirteen studies that reported the incidence of grades 3 and 4 rash showed an overall difference in the incident rash rate of 0.12 (95% CI: 0.09 to 0.14; p < 0.01) between EGFRIS and non-EGFRIS therapy. Sensitivity analyses showed that the results were generally robust, but sensitive to small samples. Conclusions: Results quantify the difference in rash rates between EGFRIS and non-EGFRIS therapy.