Efficacy and safety of tyrosine kinase inhibitor combination therapy for glioblastoma: a meta-analysis with trial sequential analysis of randomized controlled trials

Background: Tyrosine kinase inhibitors (TKIs) administered as monotherapy have demonstrated limited clinical efficacy in glioblastoma (GBM). This study synthesized evidence from existing randomized controlled trials (RCTs) to evaluate the efficacy and safety of combination treatments incorporating TKIs for GBM. Methods: We performed a systematic literature search in PubMed, the Cochrane Library, Web of Science, and Embase to identify RCTs published up to January 10, 2026. The efficacy of treatments was evaluated by progression-free survival (PFS), overall survival (OS), objective response rate (ORR), stable disease (SD), and progressive disease (PD), while safety was assessed by the incidence of adverse events (AEs). Survival outcomes were pooled as hazard ratios (HRs) and dichotomous outcomes as risk ratios (RRs), each reported with 95% confidence intervals (CIs). Heterogeneity across studies was assessed using the Cochrane Q test, I² statistic, and 95% prediction intervals (PIs). Trial sequential analysis was incorporated into the meta-analysis to control the likelihood of false-positive and false-negative conclusions. Conclusion: Our study suggests that combination regimens incorporating TKIs may have only modest therapeutic activity for GBM, showing signals of improved PFS and ORR but no OS benefit in the current evidence base. Clinicians should remain vigilant for AEs associated with these combination regimens, ensure close monitoring, and promptly implement appropriate measures to manage and mitigate toxicity. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420261293988.