Efficacy of Anti-VEGF Drugs Based Combination Therapies in Recurrent Glioblastoma: Systematic Review and Meta-Analysis.

Background: Recurrent glioblastoma multiforme (rGBM) has a grim prognosis, with current therapies offering no survival benefit. Several combination therapies involving anti-VEGF agents have been studied with mixed results.

Methods: A systematic search was performed using five electronic databases: PubMed, Scopus, ISI, Embase, and the Cochrane Library, without language limitations. The primary outcome of interest was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response ratio (ORR), and grade ≥ 3 adverse events. Estimates for PFS and OS were calculated as random effects hazard ratio (HR) with 95% confidence intervals (CIs) using the generic inverse variance method. Estimates for ORR and grade ≥ 3 adverse events were calculated using a random-effects risk ratio (RR) with 95% confidence intervals (CIs) using the Mantel-Haenszel method.

Results: Thirteen studies met the inclusion criteria and a total of 1994 patients were included in the analysis. There was no statistically significant improvement in PFS (HR 0.84; 95% CI (0.68, 1.03); I²=81%), OS (HR 0.99; 95% CI (0.88, 1.12); I²=0%), and ORR (RR 1.36; 95% CI (0.96, 1.92); I²=61%) in the combination therapy group when compared to the control group. Significantly higher grade ≥ 3 adverse events (RR 1.30; 95% CI (1.14, 1.48); I²=47%) were seen in the combination therapy when compared to the control group.

Conclusion: Our analysis showed that the use of combination therapy with anti-VEGF agents did not offer any benefit in PFS, OS, or ORR. In contrast, it had significantly higher grade 3-5 adverse events. Further studies are needed to identify effective therapies in rGBM that can improve survival.