Bevacizumab-Induced Hypertension as a Potential Physiological Clinical Biomarker for Improved Outcomes in Patients With Recurrent Glioblastoma Multiforme: A Systematic Review

Abstract

With the advancement in medicine leading to the discovery of anti-vascular endothelial growth factor drugs, numerous oncologists are now commonly using antiangiogenic medications to improve outcomes and attain disease control. Thus, the significance of prognostic and predictive indicators in patient selection has become increasingly imperative. These biomarkers have the capacity to be highly effective and can easily be implemented in various diagnostic and therapeutic settings on a large scale. Overall, it has the potential of significantly decreasing mortality in a fatal disease and possibly achieving partial or complete remission. Many clinical trials have shown the efficacy of bevacizumab in treating malignancies. However, there are currently no known predictive or prognostic biomarkers for bevacizumab in glioblastoma multiforme (GBM). Several clinical studies have evaluated bevacizumab-induced hypertension as a potential marker in patients with different malignancies, including recurrent glioblastoma multiforme (rGBM). This systematic review was performed to determine the association of bevacizumab-induced hypertension with outcomes in patients with advanced brain cancer and to assess whether hypertension (HTN) can be used as a prognostic factor. The review was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, and the databases were searched from January 2012 to June 2022. This review aimed to evaluate six published studies to investigate the relationship between hypertension and the outcomes of patients with rGBM treated with bevacizumab. Among the included publications, four out of six were retrospective and featured a positive result regarding hypertension being used as an independent predictive factor of survival outcomes in rGBM. However, two studies showed negative results. This can be attributed to the limited subsets of patients and the duration of the studies. In conclusion, bevacizumabinduced hypertension may represent a prognostic factor in patients with rGBM.

Bevacizumab-Induced Hypertension in Glioblastoma Patients and Its Potential as a Modulator of Treatment Response

“…The most reported adverse event following administration of bevacizumab is hypertension (grade 2–3), which affects ≈40% of treated patients 24–27,38,39 (Figure 1B). Interestingly, with the exception of 1 small prospective study, 38 patients who developed hypertension following bevacizumab treatment demonstrated prolonged progression-free survival and OS, with statistically significant increases in OS ranging from 5 to 9 months compared with normotensive patients.…”

“…36 This is because bevacizumab stabilizes the vasculature by inhibiting VEGFA-induced vessel permeabilization, 37 and thereby restores blood-brain barrier integrity, leading to skewed magnetic resonance imaging readouts due to marked decreases of hyperperfusion, edema, and contrast enhancement. 36 The most reported adverse event following administration of bevacizumab is hypertension (grade 2-3), which affects ≈40% of treated patients [24][25][26][27]38,39 (Figure 1B). Interestingly, with the exception of 1 small prospective study, 38 patients who developed hypertension following bevacizumab treatment demonstrated prolonged progression-free survival and OS, with statistically significant increases in OS ranging from 5 to 9 months compared with normotensive patients.…”

“…[24][25][26][27] Furthermore, bevacizumab-induced hypertension was shown by multivariate analysis to independently predict improved OS. [24][25][26][27]39 It is, therefore, possible that the inconsistencies of reported bevacizumab efficacy across different clinical trials may be a result of the large proportion of nonresponders statistically masking the benefit experienced by the smaller cohort of responders. Given these findings, it is now urgent to identify which patients will derive the most benefit from bevacizumab.…”