Receptor Tyrosine Kinase Targeted Therapies in Glioblastoma: A Systematic Review

Introduction Glioblastoma is the most common primary central nervous system malignancy and has a median survival of 14.6 months. Receptor tyrosine kinase (RTKs) signalling consitutes one of the three major pathways driving glioblastoma, implicating them as a therapeutic target. However, no individual study has yet demonstrated significant survival benefit of RTK-directed therapy. The aim of this systematic review was to synthesise the current evidence on the survival efficacy of RTK-directed therapies in human glioblastoma. Methods Studies reporting survival outcomes for human glioblastoma patients receiving any RTK-directed therapy were included. PRISMA guidelines were followed. MEDLINE, Embase, Web of Science and Scopus were searched from inception to May 2025. Citation searching of all included studies was performed for additional eligible studies. Duplicate title/abstract screening, data extraction and risk of bias assessments were conducted. Results A total of 135 studies were included in the review, 66.7% (90/135) of which studied recurrent glioblastoma. Studies included 9,029 patients, 51.1% (4612/9029) of which were male. A total of 47 different RTK-directed therapies were assessed. Multikinase inhibitors (40.7%, 55/135), EGFR-directed therapies (28.9%, 39/135) and VEGFR inhibitors (20%, 27/135) were the most studied therapies. An additional 6.7% (9/135) of studies investigated combined EGFR-directed therapy and VEGFR inhibition. A total of 3.7% (5/135) of studies demonstrated a statistically significant survival benefit, whilst therapies appeared beneficial to survival in an additional 11.1% (15/135) of studies. There was no consistent evidence supporting survival efficacy for any RTK-directed therapy. Conclusion Whilst there is no strong evidence for survival benefit of any RTK-directed therapy, there are encouraging results in a small proportion of studies. Future directions include identifying and validating novel biomarkers, standardising reporting, and improving clinical trial design to produce more robust and interpretable data.