The safety and efficacy of tyrosine kinase inhibitors against EGFR in patients with glioma; A systematic review, meta-analysis, and sub-group analysis on glioblastoma

Abstract

Background

Gliomas, particularly glioblastoma (GBM), remain challenging to treat and have a poor prognosis. Tyrosine kinase inhibitors (TKIs) targeting EGFR have shown promise, but their efficacy in gliomas is not well established. This study aimed to systematically review and meta-analyze the safety and efficacy of EGFR TKIs in patients with glioma, specifically for primary and recurrent GBM.

Methods

A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Web of Science up to January 1, 2024. Randomized controlled trials and observational studies evaluating TKIs in glioma patients were included. Primary outcomes were overall survival (OS), progression-free survival (PFS), and adverse events. A random-effects meta-analysis was performed to pool results. All statistical analysis was performed using STATA v.17.

Results

A total of 2,424 patients from 51 studies were included. The pooled mean OS was 12.68 months (95 % CI: 6.29–19.08) with 1-year and 2-year OS rates of 43 % (95 % CI: 34 %-52 %) and 14 % (95 % CI: 8 %-20 %), respectively. The mean PFS was 9.61 months (95 % CI: 4.83–14.38). The overall response rate was 19 % (95 % CI: 1 %-36 %). Grade ≥ 3 adverse events occurred in 35 % of patients (95 % CI: 13 %-57 %). Subgroup analyses revealed that combination therapies outperformed TKI monotherapy, and some newer TKIs, like vandetanib, showed improved efficacy.

Conclusions

TKIs demonstrate modest but meaningful benefits in glioma treatment, particularly when combined with other therapies. While initial survival improvements are observed, long-term outcomes remain challenging. Further research is needed to develop more potent, brain-penetrant TKIs and optimize combination strategies to improve outcomes in glioma patients.