Rash associated with epidermal growth factor receptor inhibitors: a systematic review and meta-analysis of 194 randomized controlled trials

Abstract

Background Rashes in patients treated with epidermal growth factor receptor inhibitors (EGFRIs) are closely related to better clinical outcomes. Multiple randomized controlled trials have evaluated rashes caused by EGFRIs. We conducted a meta-analysis of patients with tumors receiving EGFR-targeted therapy to determine the incidence and relative risk of rashes associated with these drugs. Methods Four databases (PubMed, Web of Science, Embase, and Cochrane) were systematically searched to find randomized controlled trials reporting the incidence of rash associated with EGFRIs from the time of database construction to May 15, 2025. Meta-analysis was used to calculate the total incidence and relative risk (RR) of all grades or each grade of rash. Results A total of 65,116 patients from 194 studies were included. The pooled incidences of all-grade rash and high-grade rash associated with EGFRIs were 52.30% (95% CI: 48.70%-55.80%) and 9.50% (95% CI: 8.70%-10.30%), respectively. The pooled RR suggested that EGFRIs were associated with a significantly increased risk of rash. Subgroup analysis and regression analysis showed that Asian populations, EGFR monoclonal antibodies (EGFR mAbs), phase III clinical trials, and EGFRI combination therapy may increase the occurrence of rash, whereas Aumolertinib had a significantly lower RR of rash. The type of tumor and the year of publication had no significant effect on the incidence of rash. The trim-and-fill method indicated that the results were reliable. Conclusions EGFRIs have a high possibility of increasing the risk of rashes. Prevention and early treatment of rashes could be performed earlier for Asian patients who use EGFR mAbs in combination with radiotherapy and chemotherapy. System Review Registration https://www.crd.york.ac.uk/PROSPERO/view/ , identifier CRD420251039464.