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

Abstract

Background

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.

Methods

Eligible studies were enrolled after a systematic search of electronic databases. A fixed-effects or random-effects model was utilized according to the heterogeneity.

Results

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 ≥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.

Conclusions

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.

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