Effectiveness of Vascular Endothelial Growth Factor Inhibitors in the Treatment of Glioblastoma: A Systematic Review and Meta-Analysis

Abstract

The purpose - was to perform a meta-analysis based on the results of randomized controlled trials that examined the efficacy and safety of using anti-VEGF (vascular endothelial growth factor (vascular endothelial growth factor, VEGF)) drugs as an auxiliary treatment for patients with glioblastoma (GBM). Material and methods. A search for randomized controlled trials was conducted in the Pubmed, EMBASE, eLibrary and Cohrane Library databases published from January 2008 to March 2019, which examined the efficacy and safety of using anti-VEGF agents as an auxiliary method of treating GBM patients. The odds ratio (OR) and 95% confidence interval (CI) were used to calculate the overall survival and progression-free survival values. Results. According to the eligibility criteria, 9 randomized controlled trials included in this meta-analysis that examine the results of using anti-VEGF drugs in 3189 patients with GBM. The overall survival rates of patients with GBM using anti-VEGF therapy exceed those in the group of patients with standard therapy without statistically significant differences (OR=0.89, 95% CI: 0.76, 1.04, p=0.13). Significant differences in progression-free survival were noted in favor of anti-VEGF agents (OR=0.70, 95% CI: 0.60, 0.82, p<0.00001). The performed subgroup analysis showed the absence of a statistically significant effect of bevacizumab on the overall survival rates of patients with GBM (OR=0.89, 95% CI: 0.75, 1.06, p=0.20). Using a combination of bevacizumab and standard therapy can significantly improve the progression-free survival rates in patients with GBM (OR=0.63, 95% CI: 0.51, 0.78, p<0.0001). Conclusion. The performed meta-analysis clearly demonstrated that the combination of anti-VEGF agents and standard therapy does not significantly increase the overall survival rate of patients with GBM. However, the use of anti-VEGF drugs statistically significantly improves the values of progression-free survival in patients with GBM.

Molecular and cellular mechanisms of glioblastoma resistance to vascular endothelial growth factor inhibitors

“…Эффективность использования анти-VEGFлекарственных средств в терапии глиобластомы наглядно продемонстрирована в ряде рандомизированных контролируемых клинических исследований, а также подтверждена в систематических обзорах и метаанализах [9][10][11]. Однако широкое применение анти-VEGF препаратов в нейроонкологической практике привело к развитию резистентности глиобластомы к лекарственным препаратам данной группы [12].…”

“…[60] отмечено, что использование антиангиогенных препаратов in vitro способствует мезенхимальной трансформации глиобластомы, имеющей более быстрый и агрессивный рост. Однако результаты последних крупных рандомизированных контролируемых клинических исследований, систематических обзоров и метаанализов наглядно продемонстрировали отсутствие различий в общей выживаемости пациентов, принимающих стандартную химиолучевую терапию и комбинацию последней c бевацизумабом [9][10][11]61]. Учитывая результаты данных исследований, можно утверждать, что применение анти-VEGF-агентов не приводит к трансформации глиобластомы в более агрессивный фенотип.…”