Skip to main content
Log in

Bevacizumab in the Treatment of Ovarian Cancer

  • Review
  • Published:
Advances in Therapy Aims and scope Submit manuscript

Abstract

Introduction

In the past decade there have been many attempts to improve systemic treatment and thus the outcome of patients with ovarian cancer. However, neither the sequential addition of non cross-resistant drugs to standard chemotherapy comprising carboplatin and paclitaxel, nor triplet combination therapies with conventional chemotherapeutic drugs have improved outcomes. Instead, such approaches have led to an increase in the incidence of side effects. We are currently experiencing a shift toward the addition of molecularly targeted and biological anticancer therapies to standard treatment. Vascular endothelial growth factor (VEGF), which improves vitally important tumor vasculature, is secreted by a range of tumors, and a high level of VEGF is known to be an independent risk factor for aggressive disease in ovarian cancer. This finding led to the development in the 1990s of bevacizumab, a humanized monoclonal antibody against VEGF.

Discussion

Several phase II trials and four phase III trials have demonstrated that bevacizumab is active in patients with advanced and recurrent ovarian cancer. Both phase III trials of bevacizumab as first-line therapy in advanced ovarian cancer (ICON 7/AGOOVAR 11 and GOG-0218) have shown that the addition of bevacizumab to chemotherapy and as maintenance therapy improves progressionfree survival (PFS). The phase III trials in platinum-sensitive (OCEANS) and platinumresistant, relapsed disease (AURELIA) have also demonstrated a benefit for bevazicumab with respect to PFS. The administration of bevacizumab to improve survival in patients with ovarian cancer is not without side effects and a broad discussion on the cost-effectiveness of this approach is ongoing.

Conclusion

This article presents clinical trial data on bevacizumab in the treatment of ovarian cancer and discusses the indication and pitfalls in the application of bevacizumab in patients with this malignancy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Kober J. The reluctant surgeon. A biography of John Hunter. Garden City, New York: Doubleday & Company, Inc.; 1960.

    Google Scholar 

  2. Thiersch C. Der Epithelialkrebs namentlich der Haut mit Atlas. Leipzig: 1865.

  3. Sandison J. The transparent chamber of the rabbits ear, giving a complete description of improved technic of construction and introduction, and general account of growth and behavior of living cells and tissues as seen with the microscope. Am J Anat. 1928;41:447–472.

    Article  Google Scholar 

  4. Ide A, Baker N, Warren S, et al. Vascularization of the Brown-Pearce rabbit epitheioma transplant as seen in the transparent ear chamber. Am J Roentgenol. 1939;42:891–899.

    Google Scholar 

  5. Folkman J, Merler E, Abernathy C, Williams G. Isolation of a tumor factor responsible for angiogenesis. J Exp Med. 1971;133:275–288.

    Article  PubMed  CAS  Google Scholar 

  6. Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun. 1989;161:851–858.

    Article  PubMed  CAS  Google Scholar 

  7. 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;57:4593–4599.

    PubMed  CAS  Google Scholar 

  8. Cannistra SA. Cancer of the ovary. N Engl J Med. 2004;351:2519–2529.

    Article  PubMed  CAS  Google Scholar 

  9. du Bois A, Reuss A, Pujade-Lauraine E, Harter P, Ray-Coquard I, Pfisterer J. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGOOVAR) and the Groupe d’Investigateurs Nationaux Pour les Etudes des Cancers de l’Ovaire (GINECO). Cancer. 2009;115:1234–1244.

    Article  PubMed  Google Scholar 

  10. Vergote I, Trope CG, Amant F, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363:943–953.

    Article  PubMed  CAS  Google Scholar 

  11. du Bois A, Luck HJ, Meier W, et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst. 2003;95:1320–1329.

    Article  PubMed  Google Scholar 

  12. Ozols RF, Bundy BN, Greer BE, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2003;21:3194–3200.

    Article  PubMed  CAS  Google Scholar 

  13. Mahner S, Woelber L, Eulenburg C, et al. TIMP-1 and VEGF-165 serum concentration during first-line therapy of ovarian cancer patients. BMC Cancer. 2010;10:139.

    Article  PubMed  Google Scholar 

  14. Cooper BC, Ritchie JM, Broghammer CL, et al. Preoperative serum vascular endothelial growth factor levels: significance in ovarian cancer. Clin Cancer Res. 2002;8:3193–3197.

    PubMed  CAS  Google Scholar 

  15. Gadducci A, Ferdeghini M, Fanucchi A, et al. Serum preoperative vascular endothelial growth factor (VEGF) in epithelial ovarian cancer: relationship with prognostic variables and clinical outcome. Anticancer Res. 1999;19:1401–1405.

    PubMed  CAS  Google Scholar 

  16. Mabuchi S, Terai Y, Morishige K, et al. Maintenance treatment with bevacizumab prolongs survival in an in vivo ovarian cancer model. Clin Cancer Res. 2008;14:7781–7789.

    Article  PubMed  CAS  Google Scholar 

  17. du Bois A, Rochon J, Lamparter C, et al. Die Qualität der Therapie des Ovarialkarzinoms in Deutschland. Frauenarzt. 2 2009;50:742–751.

    Google Scholar 

  18. Penson RT, Dizon DS, Cannistra SA, et al. Phase II study of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab as first-line chemotherapy for advanced mullerian tumors. J Clin Oncol. 2010;28:154–159.

    Article  PubMed  CAS  Google Scholar 

  19. Brown JV III, Micha JP, Rettenmaier MA, Abaid LN, Lopez KL, Goldstein BH. A pilot study evaluating a novel regimen comprised of carboplatin, paclitaxel, and bevacizumab for advancedstage ovarian carcinoma. Int J Gynecol Cancer. 2010;20:1132–1136.

    Article  PubMed  Google Scholar 

  20. Micha JP, Goldstein BH, Rettenmaier MA, et al. A phase II study of outpatient first-line paclitaxel, carboplatin, and bevacizumab for advanced-stage epithelial ovarian, peritoneal, and fallopian tube cancer. Int J Gynecol Cancer. 2007;17:771–776.

    Article  PubMed  CAS  Google Scholar 

  21. Konner JA, Grabon DM, Gerst SR, et al. Phase II study of intraperitoneal paclitaxel plus cisplatin and intravenous paclitaxel plus bevacizumab as adjuvant treatment of optimal stage II/III epithelial ovarian cancer. J Clin Oncol. 2011;29:4662–4668.

    Article  PubMed  CAS  Google Scholar 

  22. Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473–2483.

    Article  PubMed  CAS  Google Scholar 

  23. Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365:2484–2496.

    Article  PubMed  CAS  Google Scholar 

  24. AGO Study Group. Evaluation of Optimal Initial Treatment Duration of Bevacizumab in Combination With Standard Chemotherapy in Patients With Ovarian Cancer (BOOST). ClinicalTrials no. NCT01462890. Available at: http://clinicaltrials.gov/ct2/show/NCT01462890. Accessed June 2012.

  25. Heitz F, du Bois A, Kurzeder C, et al. Surgery for recurrent ovarian cancer. Womens Health (Lond Engl). 2011;7:529–535.

    Article  Google Scholar 

  26. AGO Study group. Study Comparing Tumor Debulking Surgery Versus Chemotherapy Alone in Recurrent Platinum-Sensitive Ovarian Cancer (DESKTOP III). (NCT01166737). Available at: http://clinicaltrials.gov/ct2/show/NCT01166737. Accessed July 2012.

  27. GOG. Carboplatin and Paclitaxel With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer. (NCT00565851). Available at: http://clinicaltrials.gov/ct2/show/NCT00565851. Accessed July 2012.

  28. Stuart GC, Kitchener H, Bacon M, et al. 2010 Gynecologic Cancer InterGroup (GCIG) Consensus Statement on Clinical Trials in Ovarian Cancer: Report From the Fourth Ovarian Cancer Consensus Conference. Int J Gynecol Cancer. 2011;21:750–755.

    Article  PubMed  Google Scholar 

  29. Meier W, du Bois A, Reuss A, et al. Topotecan versus treosulfan, an alkylating agent, in patients with epithelial ovarian cancer and relapse within 12 months following 1st-line platinum/paclitaxel chemotherapy. A prospectively randomized phase III trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR). Gynecol Oncol. 2009;114:199–205.

    Article  PubMed  CAS  Google Scholar 

  30. Mutch DG, Orlando M, Goss T, et al. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007;25:2811–2818.

    Article  PubMed  CAS  Google Scholar 

  31. Ferrandina G, Ludovisi M, Lorusso D, et al. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol. 2008;26:890–896.

    Article  PubMed  CAS  Google Scholar 

  32. ten Bokkel Huinink W, Gore M, Carmichael J, et al. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol. 1997;15:2183–2193.

    PubMed  Google Scholar 

  33. Parmar MK, Ledermann JA, Colombo N, et al. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003;361:2099–2106.

    Article  PubMed  CAS  Google Scholar 

  34. Pfisterer J, Plante M, Vergote I, et al. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J Clin Oncol. 2006;24:4699–4707.

    Article  PubMed  CAS  Google Scholar 

  35. Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, et al. Pegylated liposomal doxorubicin and carboplatin compared with paclitaxel and carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol. 2010;28:3323–3329.

    Article  PubMed  CAS  Google Scholar 

  36. Thigpen T, duBois A, McAlpine J, et al. First-line therapy in ovarian cancer trials. Int J Gynecol Cancer. 2011;21:756–762.

    Article  PubMed  Google Scholar 

  37. Cannistra SA, Matulonis UA, Penson RT, et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol. 2007;25:5180–5186.

    Article  PubMed  CAS  Google Scholar 

  38. Garcia AA, Hirte H, Fleming G, et al. Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. J Clin Oncol. 2008;26:76–82.

    Article  PubMed  CAS  Google Scholar 

  39. Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007;25:5165–5171.

    Article  PubMed  CAS  Google Scholar 

  40. Chura JC, Van Iseghem K, Downs LS Jr, Carson LF, Judson PL. Bevacizumab plus cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer. Gynecol Oncol. 2007;107:326–330.

    Article  PubMed  CAS  Google Scholar 

  41. Nimeiri HS, Oza AM, Morgan RJ, et al. Efficacy and safety of bevacizumab plus erlotinib for patients with recurrent ovarian, primary peritoneal, and fallopian tube cancer: a trial of the Chicago, PMH, and California Phase II Consortia. Gynecol Oncol. 2008;110:49–55.

    Article  PubMed  CAS  Google Scholar 

  42. Smerdel MP, Waldstrom M, Brandslund I, Steffensen KD, Andersen RF, Jakobsen A. Prognostic importance of vascular endothelial growth factor-A expression and vascular endothelial growth factor polymorphisms in epithelial ovarian cancer. Int J Gynecol Cancer. 2009;19:578–584.

    Article  PubMed  Google Scholar 

  43. Kudoh K, Takano M, Kouta H, et al. Effects of bevacizumab and pegylated liposomal doxorubicin for the patients with recurrent or refractory ovarian cancers. Gynecol Oncol. 2011;122:233–237.

    Article  PubMed  CAS  Google Scholar 

  44. Muggia FM, Boyd L, Liebes L, et al. Pegylated liposomal doxorubicin (PLD) with bevacizumab (B) in second-line treatment of ovarian cancer (OC): pharmacokinetics (PK), safety, and preliminary outcome results. J Clin Oncol 2009;27(Suppl.): 15s (abstr 5548).

    Google Scholar 

  45. McGonigle KF, Muntz HG, Vuky J, et al. Combined weekly topotecan and biweekly bevacizumab in women with platinumresistant ovarian, peritoneal, or fallopian tube cancer: results of a phase 2 study. Cancer. 2011;117:3731–3740.

    Article  PubMed  CAS  Google Scholar 

  46. Del Carmen MG, Micha J, Small L, Street DG, Londhe A, McGowan T. A phase II clinical trial of pegylated liposomal doxorubicin and carboplatin plus bevacizumab in patients with platinumsensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer. Gynecol Oncol. 2012;126:369–374.

    Article  PubMed  Google Scholar 

  47. Aghajanian C, Finkler N, Rutherford T, et al. OCEANS: a randomized, double-blinded, placebocontrolled phase III trial of chemotherapy with or without bevacizumab (BEV) in patients with platinum-sensitive recurrent epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC). J Clin Oncol. 2011;29(Suppl.). Abstract LBA 5007.

  48. Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G. AURELIA: a randomized phase III trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum (PT)-resistant recurrent ovarian cancer (OC). J Clin Oncol 2012;30(Suppl.). Abstract LBA 5002.

  49. Hensley ML. Big costs for little gain in ovarian cancer. J Clin Oncol. 2011;29:1230–1232.

    Article  PubMed  Google Scholar 

  50. Cohn DE, Kim KH, Resnick KE, O’Malley DM, Straughn JM Jr. At what cost does a potential survival advantage of bevacizumab make sense for the primary treatment of ovarian cancer? A cost-effectiveness analysis. J Clin Oncol. 2011;29:1247–1251.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Florian Heitz.

Additional information

To view enhanced content go to www.advancesintherapy.com

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heitz, F., Harter, P., Barinoff, J. et al. Bevacizumab in the Treatment of Ovarian Cancer. Adv Therapy 29, 723–735 (2012). https://doi.org/10.1007/s12325-012-0041-9

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-012-0041-9

Keywords

Navigation