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).

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).

see Bevacizumab for recurrent 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).

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).

see Bevacizumab for meningioma

see Bevacizumab for neurofibromatosis type 2

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).

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

Genentech Study Showed That Avastin Helped People with Newly Diagnosed Glioblastoma Live Longer without Their Disease Worsening When Added to Radiation and Chemotherapy. 2012
Gilbert MR, Dignam J, Won M, Blumenthal DT, et al. RTOG 0825: Phase III double-blind placebo- controlled trial evaluating bevacizumab in patients with newly diagnosed glioblastoma. J Clin Oncol. 2013; 31
Yang SB, Gao KD, Jiang T, Cheng SJ, Li WB. Bevacizumab combined with chemotherapy for glioblastoma: a meta-analysis of randomized controlled trials. Oncotarget. 2017 Apr 7. doi: 10.18632/oncotarget.16924. [Epub ahead of print] PubMed PMID: 28446727.
Soffietti R, Trevisan E, Rudà R. What have we learned from trials on antiangiogenic agents in glioblastoma? Expert Rev Neurother. 2014 Jan;14(1):1-3. doi: 10.1586/14737175.2014.873277. PubMed PMID: 24417499.
Wang W, Sivakumar W, Torres S, Jhaveri N, Vaikari VP, Gong A, Howard A, Golden EB, Louie SG, Schönthal AH, Hofman FM, Chen TC. Effects of convection-enhanced delivery of bevacizumab on survival of glioma-bearing animals. Neurosurg Focus. 2015 Mar;38(3):E8. doi: 10.3171/2015.1.FOCUS14743. PubMed PMID: 25727230.
Abrams DA, Hanson JA, Brown JM, Hsu FP, Delashaw JB Jr, Bota DA. Timing of surgery and bevacizumab therapy in neurosurgical patients with recurrent high grade glioma. J Clin Neurosci. 2014 Dec 3. pii: S0967-5868(14)00562-1. doi: 10.1016/j.jocn.2014.05.054. [Epub ahead of print] Review. PubMed PMID: 25481268.
Perez-Torres CJ, Yuan L, Schmidt RE, Rich KM, Drzymala RE, Hallahan DE, Ackerman JJ, Garbow JR. Specificity of vascular endothelial growth factor treatment for radiation necrosis. Radiother Oncol. 2015 Sep 12. pii: S0167-8140(15)00462-4. doi: 10.1016/j.radonc.2015.09.004. [Epub ahead of print] PubMed PMID: 26376163.
Scholz A, Harter PN, Cremer S, Yalcin BH, Gurnik S, Yamaji M, Di Tacchio M, Sommer K, Baumgarten P, Bähr O, Steinbach JP, Trojan J, Glas M, Herrlinger U, Krex D, Meinhardt M, Weyerbrock A, Timmer M, Goldbrunner R, Deckert M, Braun C, Schittenhelm J, Frueh JT, Ullrich E, Mittelbronn M, Plate KH, Reiss Y. Endothelial cell-derived angiopoietin-2 is a therapeutic target in treatment-naive and bevacizumab-resistant glioblastoma. EMBO Mol Med. 2015 Dec 14. pii: e201505505. doi: 10.15252/emmm.201505505. [Epub ahead of print] PubMed PMID: 26666269.
  • bevacizumab.txt
  • Last modified: 2019/07/28 17:00
  • by administrador