Efficacy and safety of bevacizumab in combination with radiotherapy and temozolomide in patients with glioblastoma: A meta-analysis and meta-regression of randomized controlled trials.

Abstract

2057 Background: Glioblastoma (GBM), the most common primary brain tumor in adults, has a poor prognosis despite standard treatment. This meta-analysis evaluates the efficacy and safety of Bevacizumab, a VEGF inhibitor, when combined with radiotherapy and Temozolomide in terms of progression-free survival (PFS), overall survival (OS), and treatment-related adverse events. Methods: A systematic search of PubMed, Cochrane Library, Embase, and ClinicalTrials.gov identified randomized controlled trials (RCTs) evaluating Bevacizumab with radiotherapy and Temozolomide. Ten RCTs involving 4,425 patients (2,249 in the Bevacizumab arm and 2,176 in the control arm) met the inclusion criteria. A random-effects model calculated mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI). Results: Bevacizumab significantly improved PFS by a mean difference of 2.39 months (95% CI: 1.34 to 3.44; P = 0.0005), but no significant benefit was observed in OS (MD: 0.46 months, 95% CI: -0.53 to 1.45; P = 0.318). The therapy increased the risk of vascular adverse events (RR: 1.52, 95% CI: 1.10 to 2.11; P = 0.023). While trends towards increased hematologic adverse events (RR: 1.24, 95% CI: 0.95 to 1.60; P = 0.093) and hypertensive events (RR: 2.17, 95% CI: 0.91 to 5.16; P = 0.066) were observed, they did not reach statistical significance. Other adverse events, including serious adverse events (RR: 1.21, 95% CI: 0.84 to 1.76; P = 0.221), grade 3-4 thrombocytopenia (RR: 1.05, 95% CI: 0.44 to 2.52; P = 0.858), visceral perforation (RR: 1.92, 95% CI: 0.54 to 6.90; P = 0.202), and thromboembolic incidents (RR: 1.32, 95% CI: 0.88 to 2.00; P = 0.120), showed no significant increase. Meta-regression analysis indicated that study-level covariates, including patient age, sex distribution, and histologic differences did not significantly influence the primary outcomes. However, MGMT methylation status demonstrated borderline significance (P < 0.1), suggesting potential prognostic relevance. Conclusions: Bevacizumab modestly improves PFS but not OS, with an increased risk of vascular toxicities. Personalized treatment strategies and further research are essential to optimize its role in glioblastoma management. Adverse event outcomes associated with bevacizumab in glioblastoma patients. Adverse Event Outcomes RR 95%CI P value Any Adverse events 1.18 [0.64,2.16] 0.364 Hematologic adverse events 1.24 [0.95,1.60] 0.093 Any serious adverse events 1.21 [0.84,1.76] 0.221 Any vascular adverse events 1.52 [1.10,2.11] 0.023 Any grade 3-4 thrombocytopenia 1.05 [0.44,2.52] 0.858 Visceral perforation 1.92 [0.54,6.90] 0.202 Any arterial or venous thromboembolic incidents 1.32 [0.88,2.00] 0.120 Any hypertensive events 2.17 [0.91,5.16] 0.066