Skip to main content

Advertisement

SpringerLink
Log in

Patterns of use and outcomes of adjuvant bevacizumab therapy prior to regulatory approval in women with newly diagnosed ovarian cancer

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

Abstract

Purpose

We used real-world claims data to assess the utility of the relatively novel therapeutic bevacizumab in patients with newly diagnosed ovarian cancer in the United States after release of clinical data but prior to FDA approval.

Methods

We used the IQVIA Pharmetrics Plus commercial claims database to identify women with a new diagnosis of ovarian cancer who underwent primary surgery or neoadjuvant chemotherapy followed by interval surgery from 2006 to 2018. We calculated the rate of use of bevacizumab, and the relative frequency of hospital and emergency department (ED) admissions. Treatment-related toxicities, and time to second line chemotherapy were calculated.

Results

Among 8923 women who met study parameters, 533 (6.0%) received bevacizumab. The rate of use increased over time from 1.5% in 2006 to 7.0% in 2017 (P < 0.001), with a peak of 8.6% in 2011. The use was lowest in those ≥ 70 years old (2.8%), and in the West (4.5%), and was unaffected by number of comorbidities. Over one third (35.1%) received bevacizumab for less than 3 months, and 15.9% remained on it for greater than 13 months. Bevacizumab use was not associated with hospitalization or ED admission. Toxicities included hypertension (15.0%), kidney damage (6.8%), bleeding (3.8%), venous thrombo-embolism (2.3%) and fistula (1.1%). Time from initiation of first line chemotherapy to initiation of second line therapy was 19.9 months without bevacizumab and 22.6 months with bevacizumab use.

Conclusions

Real-world patterns of upfront bevacizumab use prior to FDA approval in 2018 differed significantly from trial data.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The study utilized commercially available data.

References

  1. Siegel RL, Miller KD, Jemal A (2020) Cancer statistics, 2020. CA Cancer J Clin 70(1):7–30. https://doi.org/10.3322/caac.21590[publishedOnlineFirst:2020/01/09]

    Article  PubMed  Google Scholar 

  2. Burger RA, Sill MW, Monk BJ et al (2007) Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a gynecologic oncology group study. J Clin Oncol 25(33):5165–5171. https://doi.org/10.1200/JCO.2007.11.5345 ([publishedOnlineFirst:2007/11/21])

    Article  CAS  PubMed  Google Scholar 

  3. Pujade-Lauraine E, Hilpert F, Weber B et al (2014) Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol 32(13):1302–1308. https://doi.org/10.1200/JCO.2013.51.4489 ([publishedOnlineFirst:2014/03/19])

    Article  CAS  PubMed  Google Scholar 

  4. Coleman RL, Brady MF, Herzog TJ et al (2017) Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG oncology/gynecologic oncology group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 18(6):779–791. https://doi.org/10.1016/S1470-2045(17)30279-6 ([publishedOnlineFirst:2017/04/26])

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Aghajanian C, Blank SV, Goff BA 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. https://doi.org/10.1200/JCO.2012.42.0505 ([publishedOnlineFirst:2012/04/25])

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Burger RA, Brady MF, Bookman MA et al (2011) Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365(26):2473–2483. https://doi.org/10.1056/NEJMoa1104390 ([publishedOnlineFirst:2011/12/30])

    Article  CAS  PubMed  Google Scholar 

  7. Burger RA, Brady MF, Rhee J et al (2013) Independent radiologic review of the gynecologic oncology group study 0218, a phase III trial of bevacizumab in the primary treatment of advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer. Gynecol Oncol 131(1):21–26. https://doi.org/10.1016/j.ygyno.2013.07.100 ([publishedOnlineFirst:2013/08/03])

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Oza AM, Cook AD, Pfisterer J et al (2015) Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol 16(8):928–936. https://doi.org/10.1016/S1470-2045(15)00086-8 ([publishedOnlineFirst:2015/06/28])

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Cohn DE, Kim KH, Resnick KE et al (2011) 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 29(10):1247–1251. https://doi.org/10.1200/JCO.2010.32.1075 ([publishedOnlineFirst:2011/03/09])

    Article  PubMed  Google Scholar 

  10. Randall LM, Monk BJ (2010) Bevacizumab toxicities and their management in ovarian cancer. Gynecol Oncol 117(3):497–504. https://doi.org/10.1016/j.ygyno.2010.02.021 ([publishedOnlineFirst:2010/04/07])

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. FDA approves bevacizumab in combination with chemotherapy for ovarian cancer 2018 Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-bevacizumab-combination-chemotherapy-ovarian-cancer accessed January 4 2020.

  12. Eisenhauer EA. Real-world evidence in the treatment of ovarian cancer. Ann Oncol 2017;28(suppl_8):viii61-viii65. https://doi.org/10.1093/annonc/mdx443 [published Online First: 2017/12/13]

  13. Yu N, Xiao Y, Yi J et al (2017) Real world treatment patterns of patients with ovarian cancer receiving first line chemotherapy in the United States. Value in Health 20(9):A473

    Article  Google Scholar 

  14. Beachler DC, Lamy FX, Russo L et al (2020) A real-world study on characteristics, treatments and outcomes in US patients with advanced stage ovarian cancer. J Ovarian Res 13(1):101. https://doi.org/10.1186/s13048-020-00691-y ([publishedOnlineFirst:2020/09/02])

    Article  PubMed  PubMed Central  Google Scholar 

  15. Bertelli G, Drews F, Lutchman-Singh K (2016) Bevacizumab for ovarian cancer at high risk of progression: reproducibility of trial results in “real-world” patients. Anticancer Res 36(9):4947–4950. https://doi.org/10.21873/anticanres.11061 ([publishedOnlineFirst:2016/09/16])

    Article  PubMed  Google Scholar 

  16. Perren TJ, Swart AM, Pfisterer J et al (2011) A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365(26):2484–2496. https://doi.org/10.1056/NEJMoa1103799 ([publishedOnlineFirst:2011/12/30])

    Article  CAS  PubMed  Google Scholar 

  17. Hall M, Bertelli G, Li L et al (2020) Role of front-line bevacizumab in advanced ovarian cancer: the OSCAR study. Int J Gynecol Cancer 30(2):213–220. https://doi.org/10.1136/ijgc-2019-000512 ([publishedOnlineFirst:2019/11/30])

    Article  PubMed  Google Scholar 

  18. Marlow NM, Pavluck AL, Bian J, et al. The relationship between insurance coverage and cancer care: a literature synthesis. Research Triangle Park (NC)2009.

  19. Buckanovich RJ, Rustin G, Uppal S et al (2019) No role for maintenance bevacizumab for up-front stage IIIc (R0) ovarian cancer. J Clin Oncol 37(29):2707–2708. https://doi.org/10.1200/JCO.19.01650 ([publishedOnlineFirst:2019/08/27])

    Article  CAS  PubMed  Google Scholar 

  20. Stark D, Nankivell M, Pujade-Lauraine E et al (2013) Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the international collaboration on ovarian neoplasms (ICON7) phase 3 randomised trial. Lancet Oncol 14(3):236–243. https://doi.org/10.1016/S1470-2045(12)70567-3 ([publishedOnlineFirst:2013/01/22])

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hinde S, Epstein D, Cook A et al (2016) The cost-effectiveness of bevacizumab in advanced ovarian cancer using evidence from the ICON7 Trial. Value Health 19(4):431–439. https://doi.org/10.1016/j.jval.2016.01.013 ([publishedOnlineFirst:2016/06/22])

    Article  PubMed  Google Scholar 

  22. Barnett JC, Alvarez Secord A, Cohn DE et al (2013) Cost effectiveness of alternative strategies for incorporating bevacizumab into the primary treatment of ovarian cancer. Cancer 119(20):3653–3661. https://doi.org/10.1002/cncr.28283 ([publishedOnlineFirst:2013/08/08])

    Article  PubMed  Google Scholar 

  23. Lee JY, Kim K, Lee YS et al (2016) Treatment preferences of advanced ovarian cancer patients for adding bevacizumab to first-line therapy. Gynecol Oncol 143(3):622–627. https://doi.org/10.1016/j.ygyno.2016.10.021 ([publishedOnlineFirst:2016/10/25])

    Article  CAS  PubMed  Google Scholar 

  24. Audibert C, Perlaky A, Stuntz M et al (2017) Variability in the therapeutic management of advanced ovarian cancer patients: a five-country survey of oncologists. Drug Des Devel Ther 11:3471–3479. https://doi.org/10.2147/DDDT.S151420 ([publishedOnlineFirst:2017/12/20])

    Article  PubMed  PubMed Central  Google Scholar 

  25. Monk BJ, Lammers PE, Cartwright T, et al. Barriers to the Access of Bevacizumab in Patients with Solid Tumors and the Potential Impact of Biosimilars: A Physician Survey. Pharmaceuticals (Basel) 2017;10(1) https://doi.org/10.3390/ph10010019 [published Online First: 2017/01/31]

Download references

Funding

Funding was provided by Merck.

Author information

Authors and Affiliations

  1. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, 161 Fort Washington Ave, Suite 456, New York, NY, 10032, USA

    Charlotte R. Gamble, Ling Chen, Dawn Hershman & Jason Wright

  2. New York Presbyterian Hospital, New York, NY, USA

    Charlotte R. Gamble

  3. Joseph L. Mailman School of Public Health, Columbia University, New York, NY, USA

    Ling Chen, Dawn Hershman & Jason Wright

  4. Center for Observational and Real-World Evidence, Oncology Product Line, Merck & Co, Kenilworth, NJ, USA

    Elizabeth Szamreta & Matthew Monberg

  5. Herbert Irving Comprehensive Cancer Center, New York, NY, USA

    Dawn Hershman & Jason Wright

Authors
  1. Charlotte R. Gamble
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ling Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elizabeth Szamreta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Matthew Monberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dawn Hershman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jason Wright
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CG: project development, data analysis, manuscript writing/editing. LC: data management, data analysis, manuscript writing/editing. ES: data management, data analysis, manuscript writing/editing. MM: project development, data analysis, manuscript writing/editing. DH Project development, data analysis, manuscript writing/editing. JW: project development, data analysis, manuscript writing/editing.

Corresponding author

Correspondence to Jason Wright.

Ethics declarations

Conflicts of interest

Dr. Wright received honorary from Clovis Oncology and royalties from UpToDate.

Ethics approval

This study was approved by the Columbia University Institutional Review Board.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PPTX 50 kb)

Supplementary file2 (DOCX 56 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gamble, C.R., Chen, L., Szamreta, E. et al. Patterns of use and outcomes of adjuvant bevacizumab therapy prior to regulatory approval in women with newly diagnosed ovarian cancer. Arch Gynecol Obstet 305, 1647–1654 (2022). https://doi.org/10.1007/s00404-021-06282-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-021-06282-6

Keywords

Search

Navigation