Skip to main content

Advertisement

SpringerLink
Log in

Progression-free survival results in postmenopausal Asian women: subgroup analysis from a phase III randomized trial of fulvestrant 500 mg vs anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON)

  • Original Article
  • Published:
Breast Cancer Aims and scope Submit manuscript

Abstract

Background

The international, phase III FALCON study (NCT01602380) in postmenopausal patients with hormone receptor-positive, locally advanced/metastatic breast cancer (LA/MBC) who had not received prior endocrine therapy, demonstrated statistically significant improvement in progression-free survival (PFS) for patients who received fulvestrant 500 mg vs anastrozole 1 mg. This subgroup analysis evaluated PFS in Asian (randomized in China, Japan, or Taiwan) and non-Asian patients from the FALCON study.

Methods

Eligible patients (estrogen receptor- and/or progesterone receptor-positive LA/MBC; World Health Organization performance status 0–2; ≥ 1 measurable/non-measurable lesion[s]) were randomized. PFS was assessed via Response Evaluation Criteria in Solid Tumours version 1.1, surgery/radiotherapy for disease worsening, or death (any cause). Secondary endpoints included: objective response rate, clinical benefit rate, duration of response, and duration of clinical benefit. Consistency of effect across subgroups was assessed via hazard ratios and 95% confidence intervals (CIs) using a log-rank test. Adverse events (AEs) were evaluated.

Results

Of the 462 randomized patients, the Asian and non-Asian subgroups comprised 67 and 395 patients, respectively. In the Asian subgroup, median PFS was 16.6 and 15.9 months with fulvestrant and anastrozole, respectively (hazard ratio 0.81; 95% CI 0.44–1.50). In the non-Asian subgroup, median PFS was 16.5 and 13.8 months, respectively (hazard ratio 0.79; 95% CI 0.62–1.01). Secondary outcomes were numerically improved with fulvestrant vs anastrozole in both subgroups. AE profiles were generally consistent between Asian and non-Asian subgroups.

Conclusions

Results of this subgroup analysis suggest that treatment effects in the Asian patient subgroup are broadly consistent with the non-Asian population.

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
Fig. 3

Similar content being viewed by others

References

  1. Rugo HS, Rumble RB, Macrae E, Barton DL, Connolly HK, Dickler MN, et al. Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology Guideline. J Clin Oncol. 2016;34:3069–103.

    Article  CAS  PubMed  Google Scholar 

  2. Cardoso F, Costa A, Senkus E, Aapro M, André F, Barrios CH, et al. 3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 3). Breast. 2017;31:244–59.

    Article  CAS  PubMed  Google Scholar 

  3. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology version 2 2017: Breast Cancer. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 3 Jul 2017.

  4. Cardoso F, Costa A, Senkus E, Aapro M, Andre F, Barrios CH, et al. 3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 3). Ann Oncol. 2017;28:16–33.

    Article  CAS  PubMed  Google Scholar 

  5. US Food and Drugs Administration. Fulvestrant prescribing information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021344s029lbl.pdf. Accessed 3 Jul 2017.

  6. European Medicines Agency. Fulvestrant summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000540/WC500021174.pdf. Accessed 3 Jul 2017.

  7. US Food and Drug Administration. Fulvestrant prescribing information. https://www.azpicentral.com/faslodex/faslodex.pdf. Accessed 30 Nov 2017.

  8. AstraZeneca. Faslodex receives US FDA approval as monotherapy for expanded use in breast cancer. https://www.astrazeneca.com/media-centre/press-releases/2017/faslodex-receives-us-fda-approval-as-monotherapy-for-expanded-use-in-breast-cancer.html. Accessed 1 Sept 2017.

  9. AstraZeneca. Faslodex receives EU approval as first-line therapy for advanced breast cancer [press release]. https://www.astrazeneca.com/media-centre/press-releases/2017/faslodex-receives-eu-approval-as-first-line-therapy-for-advanced-breast-cancer-26072017.html. Accessed 1 Aug 2017.

  10. Howell A, Robertson JFR, Quaresma Albano J, Aschermannova A, Mauriac L, Kleeberg UR, et al. 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. 2002;20:3396–403.

    Article  CAS  PubMed  Google Scholar 

  11. Osborne CK, Pippen J, Jones SE, Parker LM, Ellis M, Come S, et al. 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. 2002;20:3386–95.

    Article  CAS  PubMed  Google Scholar 

  12. Xu B, Jiang Z, Shao Z, Wang J, Feng J, Song S, et al. 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. 2011;67:223–30.

    Article  CAS  PubMed  Google Scholar 

  13. Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, et al. 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. 2010;28:4594–600.

    Article  PubMed  Google Scholar 

  14. Zhang Q, Shao Z, Shen K, Li L, Feng J, Tong Z, et al. Fulvestrant 500 mg vs 250 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer: a randomized, double-blind registrational trial in China. Oncotarget. 2016;7:57301–9.

    PubMed  PubMed Central  Google Scholar 

  15. Robertson JF, Llombart-Cussac A, Rolski J, Feltl D, Dewar J, Macpherson E, et al. 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. 2009;27:4530–5.

    Article  CAS  PubMed  Google Scholar 

  16. Robertson JFR, Lindemann JPO, Llombart-Cussac A, Rolski J, Feltl D, Dewar J, et al. Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: follow-up analysis from the randomized ‘FIRST’ study. Breast Cancer Res Treat. 2012;136:503–11.

    Article  CAS  PubMed  Google Scholar 

  17. Ellis MJ, Llombart-Cussac A, Feltl D, Dewar JA, Jasiówka M, Hewson N, et al. Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: overall survival analysis from the Phase II FIRST study. J Clin Oncol. 2015;33:3781–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Robertson JFR, Bondarenko IM, Trishkina E, Dvorkin M, Panasci L, Manikhas A, et al. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet. 2016;388:2997–3005.

    Article  CAS  PubMed  Google Scholar 

  19. Ling WH, Lee SC. Inter-ethnic differences—how important is it in cancer treatment? Ann Acad Med Singap. 2011;40:356–61.

    PubMed  Google Scholar 

  20. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. 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. 2000;92:205–16.

    Article  CAS  PubMed  Google Scholar 

  21. Sekine I, Yamamoto N, Nishio K, Saijo N. Emerging ethnic differences in lung cancer therapy. Br J Cancer. 2008;99:1757–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Robertson JFR, Osborne CK, Howell A, Jones SE, Mauriac L, Ellis M, et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials. Cancer. 2003;98:229–38.

    Article  CAS  PubMed  Google Scholar 

  23. Ohno S, Rai Y, Iwata H, Yamamoto N, Yoshida M, Iwase H, et al. Three dose regimens of fulvestrant in postmenopausal Japanese women with advanced breast cancer: results from a double-blind, phase II comparative study (FINDER1). Ann Oncol. 2010;21:2342–7.

    Article  CAS  PubMed  Google Scholar 

  24. Pritchard KI, Rolski J, Papai Z, Mauriac L, Cardoso F, Chang J, et al. Results of a phase II study comparing three dosing regimens of fulvestrant in postmenopausal women with advanced breast cancer (FINDER2). Breast Cancer Res Treat. 2010;123:453–61.

    Article  CAS  PubMed  Google Scholar 

  25. Tan SH, Lee SC, Goh BC, Wong J. Pharmacogenetics in breast cancer therapy. Clin Cancer Res. 2008;14:8027–41.

    Article  CAS  PubMed  Google Scholar 

  26. Noguchi S, Masuda N, Iwata H, Mukai H, Horiguchi J, Puttawibul P, et al. Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2. Breast Cancer. 2014;21:703–14.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Lynda M. Grinsted for her contribution to the statistical analysis of these data. Medical writing support, funded by AstraZeneca, was provided by Laura Fullerton-Batten of Complete Medical Communications.

Funding

The study was funded by AstraZeneca.

Author information

Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

    Shinzaburo Noguchi

  2. Lester and Sue Smith Breast Center, Baylor Clinic, Baylor College of Medicine, Houston, TX, USA

    Matthew J. Ellis

  3. Division of Medical Sciences and Graduate Entry Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, UK

    John F. R. Robertson

  4. AstraZeneca, Cambridge, UK

    Jackie Thirlwell

  5. AstraZeneca, Gaithersburg, MD, USA

    Mehdi Fazal

  6. Fudan University Shanghai Cancer Center, Shanghai, China

    Zhimin Shao

Authors
  1. Shinzaburo Noguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew J. Ellis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John F. R. Robertson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jackie Thirlwell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mehdi Fazal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhimin Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhimin Shao.

Ethics declarations

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki, the International Conference on Harmonisation, and Good Clinical Practice Guidelines. An ethics committee or institutional review board approved the final protocol at each study site.

Informed consent

All patients provided written, informed consent.

Conflict of interest

Shinzaburo Noguchi has been an advisor for Taiho, and has received research funding from AstraZeneca, Novartis, Chugai, Daiichi-Sankyo, Takeda, Pfizer, Ono, Taiho, and Eisai, and honoraria from AstraZeneca, Novartis, and Chugai. Matthew J. Ellis holds stock and has a leadership position with Bioclassifier LLC, which derives royalties and other income from a sublicense to Nanostring LLC for PAM50-based diagnostics, including Prosigna; he has been an ad hoc consultant for, and received honoraria and research funding from, AstraZeneca, and has also been a consultant for Pfizer, Puma and Novartis. John F. R. Robertson has been a consultant for, and has received honoraria from, AstraZeneca and Bayer AG, has received research funding from AstraZeneca, Bayer AG, and Novartis, has provided expert testimony for AstraZeneca, holds stocks or other ownership with Oncimmune, and holds stock options with Carrick Therapeutics. Jackie Thirlwell is an employee of JMT Statistics Ltd, and is under contract to provide statistical support to AstraZeneca. Mehdi Fazal is an employee of AstraZeneca. Zhimin Shao has no conflicts of interest to disclose.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Noguchi, S., Ellis, M.J., Robertson, J.F.R. et al. Progression-free survival results in postmenopausal Asian women: subgroup analysis from a phase III randomized trial of fulvestrant 500 mg vs anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON). Breast Cancer 25, 356–364 (2018). https://doi.org/10.1007/s12282-018-0838-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12282-018-0838-8

Keywords

Search

Navigation