Incidence, risk and prognostic role of anti-epidermal growth factor receptor-induced skin rash in biliary cancer: a meta-analysis

Anti-epidermal growth factor receptor (EGFR)-induced skin rash is a common adverse event and is considered a prognostic factor of various cancers. However, the role of rash is rarely known in biliary cancer, possibly owing to the low incidence of this frequently fatal malignancy. We thus performed a meta-analysis to investigate the incidence, risk and prognostic significance of skin rash related to anti-EGFR treatment for biliary cancer. Eligible studies were enrolled after a systematic search of electronic databases. A fixed-effects or random-effects model was utilized according to the heterogeneity. Fourteen clinical trials published between 2006 and 2017 comprising 1,106 patients with advanced biliary cancer were included. The overall incidence of all-grade and high-grade (grade ae<yen>3) rash was 78.2% [95% confidence interval (CI) 70.4-84.3] and 11.3% (7.6-16.5), respectively. Anti-EGFR treatment correlates with a significantly increased risk of all-grade [risk ratio (RR) 7.37, 95% CI 5.11-10.64, p < 0.0001] and high-grade (RR 6.94, 95% CI 1.89-25.45, p = 0.0035) rash compared with control medication. Higher grades of skin rash correlate with a higher objective response rate (RR 3.50, 95% CI 1.47-8.33, p = 0.0048), and a longer overall [hazard ratio (HR) 0.47, 95% CI 0.31-0.71, p = 0.0003) and progression-free survival (HR 0.51, 95% CI 0.36-0.72, p = 0.0001) compared with lower grades or no rash in patients who received anti-EGFR treatment. Anti-EGFR treatment correlates with an increased risk of skin rash in advanced biliary cancer. Stratifying patients by the severity of rash may have major implications for survival benefit regarding anti-EGFR treatment for biliary cancer.