The role of bevacizumab in the treatment of glioblastoma

Abstract

Bevacizumab has been used in patients with GBM as a salvage therapy since its approval in the United States for recurrent GBM in 2009. In order to review the therapeutic effect of bevacizumab in the primary and recurrent clinical setting we have performed a systematic analysis of data from the published literature. Weighted median progression free survival and overall survival were calculated and compared to standard therapy or other experimental therapies. A qualitative analysis of the limited studies on health related quality of life and effects on steroid requirements was also undertaken. We found that the available literature supports the use of bevacizumab for prolonging PFS and OS in the recurrent setting either alone or in combination with a cytotoxic agent (P < 0.05), but does not support its use in the primary setting (P > 0.05). The survival advantage of bevacizumab compared to experimental therapy at recurrence is limited to 4 months. There is no additional benefit reported to date in health-related quality of life with the use of bevacizumab, although it may reduce steroid requirements. On average there is one side-effect event per patient and 74% of these events are grade 3 toxicity or higher. Further studies investigating the role of bevacizumab in combination with cytotoxic agents at recurrence are awaited.

Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology

“…Likewise, VEGF and its signaling pathway are the most important positive regulators of angiogenesis, acting as an effective mitogen and survival factor for GECs and impacting blood vessel integrity and permeability. The high expression of VEGF and its receptors was widely demonstrated in GBM and many other forms of cancer, leading to a monoclonal antibody to be developed against VEGF, bevacizumab (Avastin ® ), which is administered for colorectal cancer, metastatic breast cancer, and non-small cell lung cancer, as well as for relapsed forms of GBM [32]. It was demonstrated that the local high concentration of VEGF was supported by PLT contribution, as PLTs store VEGF in their α-granuli, which are released after TCIPA.…”

Metronomic capecitabine as an immune modulator in glioblastoma patients reduces myeloid-derived suppressor cells

“…In nearly 100% of cases, this approach fails, resulting in a recurrent tumor with limited therapeutic options. Few therapies are FDA-approved for patients with recurrent GBM, including lomustine, bevacizumab, carmustine wafers, and tumor-treating fields, none of which have demonstrated a marked improvement in overall survival [6][7][8][9] . Multiple other cancers have faced similar obstacles to effective treatment, but this has been recently overcome with the use of immune-modulating therapies, and as a consequence, there is interest in trying to modify the immune system in GBM.…”

A five‐CpG signature of microRNA methylation in non‐G‐CIMP glioblastoma

“…Bevacizumab, a humanized monoclonal antibody against VEGF, has been the most promising anti‐angiogenic agents for treating GBMs and was approved for recurrent GBM treatment . However, in newly diagnosed GBM patients, recent randomized trials failed to yield clear survival benefits when applied bevacizumab plus Stupp regimen, implying that proper indicators are needed for bevacizumab treatment. In this study, the miRNA methylation‐based risk subgroups were associated with differential enrichments of pro‐angiogenic gene sets (eg, hypoxia or VEGF pathways), suggesting the possibility of differential responses to bevacizumab within the risk subgroups.…”