Bevacizumab (BEV)

Bevacizumab is a monoclonal antibody that inhibits angiogenesis by clearing circulating VEGF, resulting in a decline in the contrast-enhancing tumor, which does not always correlate with treatment response.

Bevacizumab, as antibodies, were applied to inhibit tumor angiogenesis by preventing activation of vascular endothelial growth factor receptor.

Bevacizumab, is sold under the trade name Avastin (Genentech/ Roche, South San Francisco, California).

Trials

AVAglio: a phase III trial with the addition of bevacizumab to the Stupp regimen for newly diagnosed GBM ¹⁾ and RTOG 0825 (another trial of similar design) showed improved PFS, but no significant improvement on OS ²⁾.

Yang et al. analyzed four clinical trials, including 607 patients, to investigate the efficacy and safety of bevacizumab when combined with chemotherapy for the treatment of glioblastomas. Results demonstrated that bevacizumab when combined with chemotherapy improved progression-free survival (HR = 0.66; 95% CI 0.56-0.78; p < 0.00001) compared with bevacizumab or chemotherapy alone. Furthermore, overall survival showed insignificant difference between two arms (HR 0.99; 95% CI 0.8-1.21; p = 0.92). However, we found that patients treated with bevacizumab-containing therapy reported increased objective response rate (OR 1.85, 95% CI 1.17-2.93; p = 0.009), but more treatment-related adverse events (OR 1.75; 95% CI 1.09-2.83; p = 0.02) ³⁾.

Indications

Recurrent glioblastoma

see Bevacizumab for recurrent glioblastoma.

Newly diagnosed glioblastoma

Glioblastoma, an highly vascular tumor, is a seemingly ideal target for antiangiogenic therapies.

Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known.

The most common schedule is 10 mg/kg every 2 weeks.

The AVAglio trial has reported an improvement of quality of life, while the RTOG 0825 did not, and suggested a negative impact on neurocognitive functions. The GLARIUS trial, focusing on newly diagnosed glioblastoma without MGMT methylation, suggested an advantage for bevacizumab plus irinotecan. The Phase III CENTRIC trial has excluded any role for cilengitide in addiction to standard treatment in newly diagnosed glioblastoma ⁴⁾.

The administration of bevacizumab via convection enhanced delivery (CED) increases survival over that of treatment with IV bevacizumab. Thus, CED of bevacizumab alone or in combination with chemotherapy can be an effective protocol for treating gliomas ⁵⁾.

Timing of surgery and bevacizumab therapy

The optimum time between cessation of bevacizumab therapy and surgery was 4 weeks. The timing for reinitiation of bevacizumab postsurgery was at least 2 weeks. The duration of preoperative cessation of bevacizumab treatment is critical in preventing life threatening surgical complications. The interval between the surgery and reinitiation of bevacizumab can be shortened. However, more studies are needed to ascertain the exact timing of preoperative and postoperative therapy ⁶⁾.

Meningioma

see Bevacizumab for meningioma

Neurofibromatosis type 2

see Bevacizumab for neurofibromatosis type 2

Radiation induced necrosis

Radiation induced necrosis in the brain has been treated using bevacizumab.

Perez-Torres et al. validated the VEGF specificity by comparing the therapeutic efficacy of anti-VEGF with non-specific isotype control antibody. Additionally, they found that VEGF over-expression and radionecrosis developed simultaneously, which precludes preventative anti-VEGF treatment ⁷⁾.

Resistance

Combining VEGF blockade with inhibition of Angiopoietin 2 may potentially overcome resistance to bevacizumab therapy ⁸⁾.

References