Predictive value of EGFR amplification and EGFRvIII mutation in EGFR-targeted therapy for recurrent glioblastoma: a systematic review.

内容摘要

Glioblastoma (GBM) is the most aggressive and biologically heterogeneous tumor of the central nervous system, associated with dismal prognosis and frequent recurrence. Amplification of the epidermal growth factor receptor (EGFR) and EGFRvIII mutation are common alterations, yet their prognostic significance remains unclear. This systematic review evaluated whether clinical evidence supports a predictive association between EGFR amplification or EGFRvIII mutation and response to EGFR-targeted therapy in adults with recurrent GBM. PubMed, Embase and the Cochrane Library were searched (2010-2025) for studies of adults with recurrent GBM treated with EGFR-targeted therapies, with outcomes stratified by EGFR amplification and/or EGFRvIII. Screening, data extraction and risk-of-bias assessment were performed independently. Twelve studies (565 patients) met inclusion criteria. EGFR amplification was assessed in 11 studies and EGFRvIII in six using FISH, qPCR, RT-PCR, or NGS. Median overall survival ranged from 5.7 to 10.3 months and progression-free survival from 1.7 to 6.0 months, with no consistent survival benefit observed. EGFR amplification and EGFRvIII mutation have not demonstrated reliable predictive value for EGFR-targeted therapy in recurrent GBM. The available evidence is largely derived from heterogeneous, single-arm studies, limiting robust assessment of biomarker specific treatment response and therefore these alterations are not recommended to be used to guide off-trial treatment decisions in recurrent GBM.Protocol Registration: www.crd.york.ac.uk/prospero identifier is CRD420251071466. Recurrent glioblastoma is when a brain tumor called glioblastoma comes back after treatment or starts growing again after a period of improvement. Many of these tumors have changes in a gene called epidermal growth factor receptor (EGFR), including EGFR amplification and EGFRvIII mutations, but it is still unclear whether these changes help identify patients who might benefit from EGFR-targeted treatments.This review brought together the available clinical studies that looked specifically at adults with recurrent glioblastoma and EGFR-related gene changes. It focused only on studies that reported results for patients with these EGFR gene changes and the outcome of a number of different EGFR-targeted treatment protocols. Overall, the review found no clear or lasting benefit from EGFR-targeted therapies in patients with these tumor changes.The findings show that despite strong biological reasons to target EGFR, the current evidence does not support EGFR alterations as reliable markers of treatment response in recurrent glioblastoma. The review also highlights major differences in how these gene changes are tested and how trials are designed, making results hard to compare. Better standardized testing and more carefully designed clinical trials are needed to determine whether EGFR-targeted treatment has a true role in precision treatment for this disease.ARTICLE HIGHLIGHTSEGFR amplification and EGFRvIII mutation should not guide off-trial treatment in rGBM.Biomarker testing and outcome reporting remain highly heterogeneous across trials.Future trials require appropriate control arms and standardized prospective biomarker testing.