Targeting EGFR in glioblastoma: lessons from a disappointing journey. A systematic review.

Abstract

<h4>Introduction</h4>This review aims to review the efficacy and toxicity of anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in the management of glioblastoma.<h4>Evidence acquisition</h4>A systematic review was completed utilizing PubMed, Cochrane, and Embase databases up to February 2025. Boolean operators and the MeSH term "glioma" were used, along with relevant keywords related to EGFR.<h4>Evidence synthesis</h4>First- and second-generation EGFR-focused TKIs performed poorly in patients with GBM. The use of erlotinib in combination with radiotherapy, alkylating agents, and anti-angiogenic agents yielded the best outcomes in patients with newly diagnosed GBM.<h4>Conclusions</h4>EGFR-focused TKIs were largely disappointing as a treatment for GBM. Longstanding issues, including treatment resistance, tumor heterogeneity, and blood-brain barrier penetration persist. Future efforts must focus on tackling these issues, and prioritizing patient selection via biomarkers.