, Volume 70, Issue 2, pp 181–189 | Cite as


In Previously Treated Glioblastoma
  • Marit D. MoenEmail author
Adis Drug Profile


Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that binds to human vascular endothelial growth factor and inhibits angiogenesis and hence tumour growth. It is available in the US and other countries for the treatment of several types of cancer, including glioblastoma that has recurred after previous treatment.

Two prospective phase II trials have evaluated bevacizumab 10mg/kg every 2 weeks for the treatment of previously treated glioblastoma. In the randomized, noncomparative, multicentre AVF3708g trial in patients with glioblastoma in first or second relapse, the rate of progression-free survival at 6 months was 42.6% and the objective response rate was 28.2% in recipients of bevacizumab alone (n = 85). In the bevacizumab plus irinotecan treatment arm (n=82), the 6-month progression-free survival rate was 50.3% and the objective response rate was 37.8%. These rates were all significantly higher than historical control data.

In the supporting, single-arm, single-centre, phase II NCI 06-C-0064E trial of bevacizumab in patients with glioblastoma that had recurred after radiotherapy and temozolomide chemotherapy (n = 48), the rate of progression-free survival at 6 months was 29% and the overall response rate based on Macdonald criteria was 35%.

Given the nature of the disease, bevacizumab was generally well tolerated in these two phase II trials. In the AVF3708g trial, grade 3 or higher treatment-emergent adverse events occurred in 46.4% of bevacizumab and 65.8% of bevacizumab plus irinotecan recipients.


Vascular Endothelial Growth Factor Bevacizumab Irinotecan Objective Response Rate Karnofsky Performance Status 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Acknowledgements and Disclosures

The manuscript was reviewed by: H.S. Friedman, Brain Tumor Center, Duke University Medical Center, Durham, North Carolina, USA; T.N. Kreisl, Neuro-Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA; P.Y. Wen, Center for Neuro-Oncology, Dana-Farber/Brigham and Women’s Cancer Center, Boston, Massachusetts, USA.

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.


  1. 1.
    Omuro AMP, Faivre S, Raymond E. Lessons learned in the development of targeted therapy for malignant gliomas. Mol Cancer Ther 2007 Jul; 6(7): 1909–19PubMedCrossRefGoogle Scholar
  2. 2.
    Central Brain Tumor Registry of the United States (CBTRUS). Statistical report: primary brain tumors in the United States, 2007–2008 (years of data collected 2000–2004) [online]. Available from URL: [Accessed 2009 Sep 14]
  3. 3.
    National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: central nervous system cancers V.2.2009 [online]. Available from URL: [Accessed 2009 Sep 14]
  4. 4.
    Wong ET, Hess KR, Gleason MJ, et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 1999 Aug; 17(8): 2572–8PubMedGoogle Scholar
  5. 5.
    de Groot JF, Yung WKA. Bevacizumab and irinotecan in the treatment of recurrent malignant gliomas. Cancer J 2008 Sep–Oct; 14(5): 279–85PubMedCrossRefGoogle Scholar
  6. 6.
    Chaudhry IH, O’Donovan DG, Brenchley PEC, et al. Vascular endothelial growth factor expression correlates with tumour grade and vascularity in gliomas. Histopathology 2001 Oct; 39(4): 409–15PubMedCrossRefGoogle Scholar
  7. 7.
    Zhou YH, Tan F, Hess KR, et al. The expression of PAX6, PTEN, vascular endothelial growth factor, and epidermal growth factor receptor in gliomas: relationship to tumor grade and survival. Clin Cancer Res 2003 Aug 15; 9(9): 3369–75PubMedGoogle Scholar
  8. 8.
    Avastin® (bevacizumab) solution for intravenous infusion: US prescribing information. South San Francisco (CA): Genentech, Inc., 2009 JulGoogle Scholar
  9. 9.
    Scott LJ. Bevacizumab: in first-line treatment of metastatic breast cancer. Drugs 2007; 67(12): 1793–9PubMedCrossRefGoogle Scholar
  10. 10.
    Frampton JE, Keating GM. Bevacizumab: in first-line treatment of advanced and/or metastatic renal cell carcinoma. Biodrugs 2008; 22(2): 113–20PubMedCrossRefGoogle Scholar
  11. 11.
    Wagstaff AJ, Keam SJ, McCormack PL. Bevacizumab plus platinum-based chemotherapy: in advanced non-small cell lung cancer. Biodrugs 2009; 23(3): 187–96PubMedCrossRefGoogle Scholar
  12. 12.
    Lyseng-Williamson KA, Robinson DM. Bevacizumab: a review of its use in advanced colorectal cancer, breast cancer, and NSCLC. Am J Cancer 2006; 5(1): 43–60CrossRefGoogle Scholar
  13. 13.
    Chinot O, de La Motte Rouge T, Moore N, et al. Addition of bevacizumab to the multi-modality standard of care in patients with newly diagnosed glioblastoma: a phase III trial [abstract no. P-8713]. Eur J Cancer Suppl 2009 Sep; 7(2): 497CrossRefGoogle Scholar
  14. 14.
    Gerber HP, Ferrara N. Pharmacology and pharmacodynamics of bevacizumab as mono therapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res 2005 Feb 1; 65(3): 671–80PubMedGoogle Scholar
  15. 15.
    Presta LG, Chen H, O’Connor SJ, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 1997 Oct 15; 57(20): 4593–9PubMedGoogle Scholar
  16. 16.
    Wang Y, Fei D, Vanderlaan M, et al. Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro. Angiogenesis 2004; 7(4): 335–45PubMedCrossRefGoogle Scholar
  17. 17.
    Kim KJ, Li B, Winer J, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 1993 Apr 29; 362(6423): 841–4PubMedCrossRefGoogle Scholar
  18. 18.
    Gordon MS, Margolin K, Talpaz M, et al. Phase I safety and pharmacokinetic study of recombinant human antivascular endothelial growth factor in patients with advanced cancer. J Clin Oncol 2001 Feb 1; 19(3): 843–50PubMedGoogle Scholar
  19. 19.
    Shih T, Lindley C. Bevacizumab: an angiogenesis inhibitor for the treatment of solid malignancies. Clin Ther 2006 Nov;28(11): 1779–802PubMedCrossRefGoogle Scholar
  20. 20.
    Jain RK. A new target for tumor therapy. N Engl J Med 2009 Jun 18; 360(25): 2669–71PubMedCrossRefGoogle Scholar
  21. 21.
    Lu JF, Bruno R, Eppler S, et al. Clinical pharmacokinetics of bevacizumab in patients with solid tumors. Cancer Chemother Pharmacol 2008 Oct; 62(5): 779–86PubMedCrossRefGoogle Scholar
  22. 22.
    Margolin K, Gordon MS, Holmgren E, et al. Phase Ib trial of intravenous recombinant humanized monoclonal antibody to vascular endothelial growth factor in combination with chemotherapy in patients with advanced cancer: pharmacologic and long-term safety data. J Clin Oncol 2001 Feb 1; 19(3): 851–6PubMedGoogle Scholar
  23. 23.
    Denlinger CS, Blanchard R, Xu L, et al. Pharmacokinetic analysis of irinotecan plus bevacizumab in patients with advanced solid tumors. Cancer Chemother Pharmacol 2009 Dec; 65(1): 97–105PubMedCrossRefGoogle Scholar
  24. 24.
    Mahmood I. Center for Drug Evaluation and Research. Approval package for application number STN-125085/0: clinical pharmacology/TOX review [online]. Available from URL: [Accessed 2009 Sep3]
  25. 25.
    Friedman HS, Prados MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 2009 Oct 1; 27(28): 4733–40PubMedCrossRefGoogle Scholar
  26. 26.
    Kreisl TN, Kim L, Moore K, et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 2009 Feb 10; 27(5): 740–5PubMedCrossRefGoogle Scholar
  27. 27.
    US Food and Drug Administration. FDA briefing document: Oncology Drug Advisory Committee meeting; March 31, 2009; BLA STN 125085/169 Avastin® (bevacizumab) [online]. Available from URL: [Accessed 2009 Aug 12]
  28. 28.
    Macdonald DR, Cascino TL, Schold Jr SC, et al. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 1990 Jul; 8(7): 1277–80PubMedGoogle Scholar
  29. 29.
    Prados M, Cloughesy T, Samant MK, et al. Evaluation of objective response as a predictor of survival in bevacizumab-treated patients with glioblastoma at first or second relapse in the BRAIN study [abstract no. P-8721]. Eur J Cancer Suppl 2009 Sep; 7(2): 499CrossRefGoogle Scholar
  30. 30.
    Vredenburgh JJ, Wefel J, Cloughesy T, et al. Clinical assessment of corticosteroid use and neurocognitive function in patients with glioblastoma at first or second relapse treated with bevacizumab in the BRAIN study [abstract no. O-8707]. Eur J Cancer Suppl 2009 Sep; 7(2): 495CrossRefGoogle Scholar
  31. 31.
    Wefel JS, Cloughesy T, Zazzali J, et al. Neurocognitive function in patients with glioblastoma multiforme in first or second relapse treated with bevacizumab in the BRAIN study [abstract no. 2056]. J Clin Oncol 2009; 27 Suppl.: 15s. Plus poster presented at the 45th Annual Meeting of the American Society of Clinical Oncology; 2009 May 29–Jun 2; Orlando (FL)CrossRefGoogle Scholar
  32. 32.
    Higa GM, Abraham J. Biological mechanisms of bevacizumab-associated adverse events. Expert Rev Anti-cancer Ther 2009 Jul; 9(7): 999–1007CrossRefGoogle Scholar
  33. 33.
    Dietrich J, Norden AD, Wen PY. Emerging antiangiogenic treatments for gliomas: efficacy and safety issues. Curr Opin Neurol 2008 Dec; 21(6): 736–44PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  1. 1.Adis, a Wolters Kluwer BusinessMairangi Bay, North Shore 0754, AucklandNew Zealand

Personalised recommendations