Angiogenesis inhibitors effects on overall survival and progression-free survival in newly diagnosed primary glioblastoma multiforme: a meta-analysis of twelve randomized clinical trials

Background: Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Typically treated with initial surgical resection, and chemoradiotherapy, despite current treatments, patients typically survive only 12–14 months, necessitating new therapeutic approaches. Our meta-analysis evaluates combining antiangiogenic medications with chemoradiotherapy versus using chemoradiotherapy alone in treating newly diagnosed GBM. Methods: A comprehensive literature search was conducted using PubMed/MEDLINE, Scopus, Cochrane and the Web of Science databases. The search aimed to identify studies reporting overall survival (OS), progression-free survival (PFS), and hazard ratio (HR) with corresponding confidence intervals (CIs) in patients with newly diagnosed GBM. We employed random-effect meta-analysis. Results: Twelve randomized clinical trials (RCTs) involved 3,309 patients included in the study. The findings showed that angiogenesis inhibitors significantly prolonged PFS [HR 0.85, 95% CI (0.73, 0.99), p-value = 0.04], while there was no significant difference on OS [HR 1.014, 95%CI (0.89, 1.15), p-value = 0.84]. Bevacizumab (BEV) exhibited the highest [HR 0.67, 95% CI (0.56, 0.79), p-value < 0.0001] and thalidomide exhibited the lowest [HR 1.46, 95% CI (1.004, 2.1), p-value = 0.048] improvements of PFS. Meta-regression revealed that age, white race, study sample size, infection, vascular disease complications, KPS > 60, biopsy, gross and subtotal resection can significantly influenced the PFS, while only the year of publication affected OS. Conclusions: The current study showed that improve the PFS with no significant effect on OS. Our findings may provide some evidence for decision-making regarding the utilization of angiogenesis inhibitors for the treatment of adult patients with newly diagnosed GBM.