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Breast Cancer Research and Treatment

, Volume 171, Issue 3, pp 535–544 | Cite as

Efficacy and safety of fulvestrant in postmenopausal patients with hormone receptor-positive advanced breast cancer: a systematic literature review and meta-analysis

  • Jiayu Wang
  • Binghe XuEmail author
  • Wenna Wang
  • Xiaoyu Zhai
  • Xuelian Chen
Review

Abstract

Purpose

This meta-analysis was conducted to compare the efficacy and safety of fulvestrant with aromatase inhibitors in postmenopausal women with hormone receptor-positive (estrogen and/or progesterone receptor positive) advanced breast cancer.

Methods

Electronic databases were searched for randomized controlled trials comparing the efficacy and safety of fulvestrant with three aromatase inhibitors (anastrozole/letrozole/exemestane) published through August 31, 2017. Time to progression/progression-free survival was the primary outcome, while overall survival and safety were the secondary outcomes. Time to progression/progression-free survival was evaluated in subgroups determined on age, hormone receptor status, visceral metastasis, and measurable disease. Hazard ratios with 95% confidence intervals were analyzed by STATA 12.0.

Results

Total of seven randomized controlled trials, with 3168 patients were included for analysis. In the overall population, fulvestrant and aromatase inhibitors had similar time to progression/progression-free survival (Hazard ratio 0.93; 95% confidence interval 0.86–1.01, P = 0.102); however, time to progression/progression-free survival for fulvestrant 500 mg was significantly longer compared with aromatase inhibitors (hazard ratio 0.75; 95% confidence interval 0.62–0.91, P = 0.003). Subgroup analysis revealed significant prolongation of time to progression/progression-free survival with fulvestrant compared with aromatase inhibitors in the patients of estrogen and progesterone receptor-positive (hazard ratio 0.86; 95% confidence interval, 0.75–0.98, P = 0.022) and patients aged ≥ 65 years (hazard ratio 0.81; 95% confidence interval 0.68–0.96, P = 0.014). Overall survival was similar in both groups (hazard ratio 0.89; 95% confidence interval 0.70, 1.13, P = 0.334).

Conclusion

In postmenopausal women with estrogen and/or progesterone receptor-positive advanced breast cancer, fulvestrant 500 mg showed better efficacy than aromatase inhibitor, which was not seen with fulvestrant 250 mg. Compared to aromatase inhibitors, fulvestrant prolonged time to progression/progression-free survival in the subgroups including estrogen and progesterone receptor-positive patients and those aged ≥ 65 years.

Keywords

Advanced breast cancer Hormone receptor Fulvestrant Aromatase inhibitors Postmenopausal 

Notes

Acknowledgements

The authors acknowledge Dr. Priyanka Nair and Karan Sharma from Indegene Pvt. Ltd. for medical writing assistance during the development of this manuscript, as funded by AstraZeneca Pharmaceutical Company Ltd.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90.  https://doi.org/10.3322/caac.20107 CrossRefGoogle Scholar
  2. 2.
    Li T, Mello-Thoms C, Brennan PC (2016) Descriptive epidemiology of breast cancer in China: incidence, mortality, survival and prevalence. Breast Cancer Res Treat 159:395–406.  https://doi.org/10.1007/s10549-016-3947-0 CrossRefPubMedGoogle Scholar
  3. 3.
    Chen W, Zheng R, Baade PD et al (2016) Cancer statistics in China, 2015. CA Cancer J Clin 66:115–132.  https://doi.org/10.3322/caac.21338 CrossRefGoogle Scholar
  4. 4.
    Kümler I, Knoop AS, Jessing CAR et al (2016) Review of hormone-based treatments in postmenopausal patients with advanced breast cancer focusing on aromatase inhibitors and fulvestrant. ESMO Open 1:e000062.  https://doi.org/10.1136/esmoopen-2016-000062 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Rugo HS, Rumble RB, Macrae E et al (2016) Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology Guideline. J Clin Oncol 34:3069–3103.  https://doi.org/10.1200/JCO.2016.67.1487 CrossRefPubMedGoogle Scholar
  6. 6.
    Cardoso F, Costa A, Norton L et al (2014) ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2). Breast Edinb Scotl 23:489–502.  https://doi.org/10.1016/j.breast.2014.08.009 CrossRefGoogle Scholar
  7. 7.
    Mantas D, Kostakis JD, C. M (2016) Aromatase inhibitors: a comprehensive review in mechanisms of action, side effects and treatment in postmenopausal early breast cancer patients. Hell J Surg 88:245–251CrossRefGoogle Scholar
  8. 8.
    Ingle JN (2011) Overview of adjuvant trials of aromatase inhibitors in early breast cancer. Steroids 76:765–767.  https://doi.org/10.1016/j.steroids.2011.02.021 CrossRefPubMedGoogle Scholar
  9. 9.
    Osborne CK, Wakeling A, Nicholson RI (2004) Fulvestrant: an oestrogen receptor antagonist with a novel mechanism of action. Br J Cancer 90(Suppl 1):S2–S6.  https://doi.org/10.1038/sj.bjc.6601629 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
  11. 11.
    Di Leo A, Jerusalem G, Petruzelka L et al (2010) Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor–positive advanced breast cancer. J Clin Oncol 28:4594–4600.  https://doi.org/10.1200/JCO.2010.28.8415 CrossRefPubMedGoogle Scholar
  12. 12.
    Leo AD, Jerusalem G, Petruzelka L et al (2014) Final overall survival: fulvestrant 500 mg vs 250 mg in the randomized CONFIRM trial. JNCI J Natl Cancer Inst 106:djt337–djt337.  https://doi.org/10.1093/jnci/djt337 CrossRefPubMedGoogle Scholar
  13. 13.
    Valachis A, Mauri D, Polyzos NP et al (2010) Fulvestrant in the treatment of advanced breast cancer: A systematic review and meta-analysis of randomized controlled trials. Crit Rev Oncol Hematol 73:220–227.  https://doi.org/10.1016/j.critrevonc.2009.03.006 CrossRefPubMedGoogle Scholar
  14. 14.
    Telford C, Jones N, Livings C, Batson S (2016) Network meta-analysis comparing overall survival for fulvestrant 500 mg versus alternative therapies for treatment of postmenopausal, estrogen receptor-positive advanced breast cancer following failure on prior endocrine therapy. Clin Breast Cancer 16:188–195.  https://doi.org/10.1016/j.clbc.2016.02.007 CrossRefPubMedGoogle Scholar
  15. 15.
    Telford C, Takyar S, Parth J et al (2017) A network meta-analysis of fulvestrant vs alternative first-line endocrine therapies for endocrine therapy-naive postmenopausal hormone receptor-positive advanced or metastatic breast cancer. J Clin Oncol 35:e12545–e12545CrossRefGoogle Scholar
  16. 16.
    Cope S, Ouwens MJNM, Jansen JP, Schmid P (2013) Progression-free survival with fulvestrant 500 mg and alternative endocrine therapies as second-line treatment for advanced breast cancer: a network meta-analysis with parametric survival models. Value Health 16:403–417.  https://doi.org/10.1016/j.jval.2012.10.019 CrossRefPubMedGoogle Scholar
  17. 17.
    Bachelot T, McCool R, Duffy S et al (2014) Comparative efficacy of everolimus plus exemestane versus fulvestrant for hormone-receptor-positive advanced breast cancer following progression/recurrence after endocrine therapy: a network meta-analysis. Breast Cancer Res Treat 143:125–133.  https://doi.org/10.1007/s10549-013-2778-5 CrossRefPubMedGoogle Scholar
  18. 18.
    Mauri D, Pavlidis N, Polyzos NP, Ioannidis JPA (2006) Survival with aromatase inhibitors and inactivators versus standard hormonal therapy in advanced breast cancer: meta-analysis. J Natl Cancer Inst 98:1285–1291.  https://doi.org/10.1093/jnci/djj357 CrossRefPubMedGoogle Scholar
  19. 19.
    Altundag K (2006) Aromatase inhibitors in breast cancer: an overview. Oncologist 11:553–562.  https://doi.org/10.1634/theoncologist.11-6-553 CrossRefPubMedGoogle Scholar
  20. 20.
    Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097.  https://doi.org/10.1371/journal.pmed.1000097 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Higgins JPT, Altman DG, Gotzsche PC et al (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928–d5928.  https://doi.org/10.1136/bmj.d5928 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127:820–826CrossRefGoogle Scholar
  23. 23.
    Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560.  https://doi.org/10.1136/bmj.327.7414.557 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Howell A, Robertson JFR, Quaresma Albano J et al (2002) Fulvestrant, formerly ICI 182,780, Is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol 20:3396–3403.  https://doi.org/10.1200/JCO.2002.10.057 CrossRefPubMedGoogle Scholar
  25. 25.
    Osborne CK, Pippen J, Jones SE et al (2002) Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American Trial. J Clin Oncol 20:3386–3395.  https://doi.org/10.1200/JCO.2002.10.058 CrossRefPubMedGoogle Scholar
  26. 26.
    Xu B, Jiang Z, Shao Z et al (2011) Fulvestrant 250 mg versus anastrozole for Chinese patients with advanced breast cancer: results of a multicentre, double-blind, randomised phase III trial. Cancer Chemother Pharmacol 67:223–230.  https://doi.org/10.1007/s00280-010-1483-x CrossRefPubMedGoogle Scholar
  27. 27.
    Johnston SR, Kilburn LS, Ellis P et al (2013) Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial. Lancet Oncol 14:989–998.  https://doi.org/10.1016/S1470-2045(13)70322-X CrossRefPubMedGoogle Scholar
  28. 28.
    Chia S, Gradishar W, Mauriac L et al (2008) Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor–positive, Advanced Breast Cancer: Results From EFECT. J Clin Oncol 26:1664–1670.  https://doi.org/10.1200/JCO.2007.13.5822 CrossRefPubMedGoogle Scholar
  29. 29.
    Robertson JFR, Llombart-Cussac A, Rolski J et al (2009) Activity of fulvestrant 500 mg versus anastrozole 1 mg as first-line treatment for advanced breast cancer: results from the FIRST Study. J Clin Oncol 27:4530–4535.  https://doi.org/10.1200/JCO.2008.21.1136 CrossRefPubMedGoogle Scholar
  30. 30.
    Robertson JFR, Bondarenko IM, Trishkina E et al (2016) Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet 388:2997–3005.  https://doi.org/10.1016/S0140-6736(16)32389-3 CrossRefPubMedGoogle Scholar
  31. 31.
    Howell A, Robertson JFR, Abram P et al (2004) Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. J Clin Oncol 22:1605–1613.  https://doi.org/10.1200/JCO.2004.02.112 CrossRefPubMedGoogle Scholar
  32. 32.
    Clatot F, Augusto L, Di Fiore F (2017) ESR1 mutations in breast cancer. Aging 9:3–4.  https://doi.org/10.18632/aging.101165 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Reinert T, Saad ED, Barrios CH, Bines J (2017) Clinical implications of ESR1 mutations in hormone receptor-positive advanced breast cancer. Front Oncol  https://doi.org/10.3389/fonc.2017.00026 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Fribbens C, O’Leary B, Kilburn L et al (2016) Plasma ESR1 mutations and the treatment of estrogen receptor–positive advanced breast cancer. J Clin Oncol 34:2961–2968.  https://doi.org/10.1200/JCO.2016.67.3061 CrossRefPubMedGoogle Scholar
  35. 35.
    Stewart LA, Tierney JF (2002) To IPD or not to IPD?: advantages and disadvantages of systematic reviews using individual patient data. Eval Health Prof 25:76–97.  https://doi.org/10.1177/0163278702025001006 CrossRefPubMedGoogle Scholar
  36. 36.
    Turner NC, Ro J, André F et al (2015) Palbociclib in hormone-receptor–positive advanced breast cancer. N Engl J Med 373:209–219.  https://doi.org/10.1056/NEJMoa1505270 CrossRefPubMedGoogle Scholar
  37. 37.
    Finn RS, Crown JP, Lang I et al (2015) The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 16:25–35.  https://doi.org/10.1016/S1470-2045(14)71159-3 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medical Oncology, National Cancer Centre and Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

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