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Bevacizumab in the treatment of ovarian cancer: a meta-analysis from four phase III randomized controlled trials

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Background

The aim of this meta-analysis was to summarize the efficacy and safety of bevacizumab in the treatment of ovarian cancer.

Methods

We sought to identify randomised controlled trials (RCTs) by searching PubMed and Web of Science. Outcomes were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events.

Results

Four studies with 4,246 patients were included. Combination of bevacizumab and chemotherapy resulted in a statistically significant improvement in ORR (OR 2.165, 95 % CI 1.511–3.103) and in PFS (HR 0.691, 95 % CI 0.517–0.865), compared with chemotherapy alone. There was no evidence of a significant improvement in OS (HR 0.934, 95 % CI 0.826–1.041). It also had significantly increased risk of gastrointestinal events (OR 2.743, 95 % CI 1.580–4.763; P < 0.001), hypertension (OR 4.630, 95 % CI 3.737 to 5.737; P < 0.001), proteinuria (OR 4.872, 95 % CI 2.617–9.069; P < 0.001), and arterial thromboembolism (OR 1.994, 95 % CI 1.210–3.286; P = 0.007).

Conclusion

This meta-analysis suggests that the addition of bevacizumab to chemotherapy offers meaningful improvement in objective response rate and progression-free survival in ovarian cancer treatment, but does not benefit overall survival. It also significantly increased the occurrence of gastrointestinal events, hypertension, proteinuria, and arterial thromboembolism.

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References

  1. Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90

    Article  PubMed  Google Scholar 

  2. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62(1):10–29

    Article  PubMed  Google Scholar 

  3. Hennessy BT, Coleman RL, Markman M (2009) Ovarian cancer. Lancet 374(9698):1371–1382

    Article  PubMed  CAS  Google Scholar 

  4. Jelovac D, Armstrong DK (2011) Recent progress in the diagnosis and treatment of ovarian cancer. CA Cancer J Clin 61(3):183–203

    Article  PubMed  Google Scholar 

  5. Kryczek I, Lange A, Mottram P et al (2005) CXCL12 and vascular endothelial growth factor synergistically induce neoangiogenesis in human ovarian cancers. Cancer Res 65(2):465–472

    PubMed  CAS  Google Scholar 

  6. Zhang L, Yang N, Park JW et al (2003) Tumor-derived vascular endothelial growth factor up-regulates angiopoietins-2 in host endothelium and destabilizes host vasculature, supporting angiogenesis in ovarian cancer. Cancer Res 63(12):3403–3412

    PubMed  CAS  Google Scholar 

  7. Byrne AT, Ross L, Holash J et al (2003) Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model. Clin Cancer Res 9(15):5721–5728

    PubMed  CAS  Google Scholar 

  8. Ferrara N, Hillan KJ, Gerber HP et al (2004) Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 3(5):391–400

    Article  PubMed  CAS  Google Scholar 

  9. FDA Approval for bevacizumab. (Updated: 11/18/2011). http://www.cancer.gov/cancertopics/druginfo/fda-bevacizumab

  10. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216

    Article  PubMed  CAS  Google Scholar 

  11. Higgins JPT, Altman DG. Chapter 8: Assessing risk of bias in included studies. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. http://www.cochrane-handbook.org

  12. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  13. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  16. Aghajanian C, Finkler N, Rutherford T et al (2012) OCEANS: a randomized, double-blind, placebo-controlled phase iii trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 30(17):2039–2045

    Article  PubMed  CAS  Google Scholar 

  17. Pujade-Lauraine E, Hilpert F, Weber B, et al (2012) AURELIA: a randomized phase III trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum (PT)-resistant recurrent ovarian cancer (OC). http://meeting.ascopubs.org/cgi/content/short/30/18_suppl/LBA5002?rss=1. Accessed 29 Mar 2013

  18. Folkman J, Cole P, Zimmerman S (1966) Tumor behavior in isolated perfused organs: in vitro growth and metastases of biopsy material in rabbit thyroid and canine intestinal segment. Ann Surg 164:491–502

    Article  PubMed  CAS  Google Scholar 

  19. Kim KJ, Li B, Winer J et al (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362(6423):841–844

    Article  PubMed  CAS  Google Scholar 

  20. Valachis A, Polyzos NP, Patsopoulos NA, Georgoulias V, Mavroudis D, Mauri D (2010) Bevacizumab in metastatic breast cancer: a meta-analysis of randomized controlled trials. Breast Cancer Res Treat 122(1):1–7

    Article  PubMed  CAS  Google Scholar 

  21. Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349(5):427–434

    Article  PubMed  CAS  Google Scholar 

  22. Lima AB, Macedo LT, Sasse AD (2011) Addition of bevacizumab to chemotherapy in advanced non-small cell lung cancer: a systematic review and meta-analysis. PLoS One 6(8):e22681

    Article  PubMed  CAS  Google Scholar 

  23. Cao Y, Tan A, Gao F, Liu L, Liao C, Mo Z (2009) A meta-analysis of randomized controlled trials comparing chemotherapy plus bevacizumab with chemotherapy alone in metastatic colorectal cancer. Int J Colorectal Dis 24(6):677–685

    Article  PubMed  Google Scholar 

  24. Penson RT, Dizon DS, Cannistra SA et al (2010) Phase II study of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab as first-line chemotherapy for advanced mullerian tumors. J Clin Oncol 28(1):154–159

    Article  PubMed  CAS  Google Scholar 

  25. Micha JP, Goldstein BH, Rettenmaier MA, Genesen M, Graham C, Bader K, Lopez KL, Nickle M, Brown JV 3rd (2007) 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 17(4):771–776

    Article  PubMed  CAS  Google Scholar 

  26. Garcia AA, Hirte H, Fleming G et al (2008) 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 26(1):76–82

    Article  PubMed  CAS  Google Scholar 

  27. Chura JC, Van Iseghem K, Downs LS Jr et al (2007) Bevacizumab plus cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer. Gynecol Oncol 107(2):326–330

    Article  PubMed  CAS  Google Scholar 

  28. Ranpura V, Pulipati B, Chu D, Zhu X, Wu S (2010) Increased risk of high-grade hypertension with bevacizumab in cancer patients: a meta-analysis. Am J Hypertens 23(5):460–468

    Article  PubMed  CAS  Google Scholar 

  29. Zhu X, Wu S, Dahut WL, Parikh CR (2007) Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis. Am J Kidney Dis 49(2):186–193

    Article  PubMed  CAS  Google Scholar 

  30. Nalluri SR, Chu D, Keresztes R, Zhu X, Wu S (2008) Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 300(19):2277–2285

    Article  PubMed  CAS  Google Scholar 

  31. Hapani S, Chu D, Wu S (2009) Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis. Lancet Oncol 10(6):559–568

    Article  PubMed  CAS  Google Scholar 

  32. Shord SS, Bressler LR, Tierney LA, Cuellar S, George A (2009) Understanding and managing the possible adverse effects associated with bevacizumab. Am J Health Syst Pharm 66(11):999–1013

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank anonymous reviewers and the editor for several insightful comments that significantly improved the paper. We are also grateful to anonymous reviewer for correcting syntax error in the paper.

Conflicts of interest

The authors have declared no conflicts of interest.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Xi Si Road 20#, Nantong, Jiangsu, People’s Republic of China

    Qing Ye

  2. Nantong University, Qi Xiu Road 19#, Nantong, Jiangsu, People’s Republic of China

    Hong-Lin Chen

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  1. Qing Ye
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  2. Hong-Lin Chen
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Corresponding author

Correspondence to Qing Ye.

Appendix

Appendix

GI events

Hypertension

Proteinuria

Arterial TE

Venous TE

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Ye, Q., Chen, HL. Bevacizumab in the treatment of ovarian cancer: a meta-analysis from four phase III randomized controlled trials. Arch Gynecol Obstet 288, 655–666 (2013). https://doi.org/10.1007/s00404-013-2820-1

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  • DOI: https://doi.org/10.1007/s00404-013-2820-1

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