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Clinical and Translational Oncology

, Volume 20, Issue 7, pp 862–869 | Cite as

Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine-resistant advanced breast cancer in routine clinical practice

  • I. Blancas
  • M. Fontanillas
  • V. Conde
  • J. Lao
  • E. Martínez
  • M. J. Sotelo
  • A. Jaen
  • J. L. Bayo
  • F. Carabantes
  • J. J. Illarramendi
  • M. M. Gordon
  • J. Cruz
  • A. García-Palomo
  • C. Mendiola
  • E. Pérez-Ruiz
  • J. S. Bofill
  • J. M. Baena-Cañada
  • N. M. Jáñez
  • G. Esquerdo
  • M. Ruiz-Borrego
Research Article
  • 196 Downloads

Abstract

Introduction

This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data.

Materials and methods

Multicenter, retrospective, observational study conducted in Spain. Postmenopausal women with locally advanced/metastatic ER-positive breast cancer who received treatment with fulvestrant 500 mg after progression with a previous anti-estrogen therapy were eligible. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), clinical benefit rate (CBR), duration of clinical benefit (DoCB), and safety profile.

Results

A total of 263 women were evaluated (median age, 65.8 years). At a median follow-up of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS according to 1st, 2nd, 3rd, and ≥ 4th lines were 11.5, 10.6, 9.9, and 8.5 months, respectively (p = 0.0245). PFS in patients with visceral involvement was 10 months vs 10.6 months in patients without visceral involvement (p = 0.6604), 9.6 months in patients with high Ki67 vs 10 months in patients with low Ki67 (p = 0.7224), and 10.2 months in HER2+ patients vs 10.3 months in HER2− patients (p = 0.6809). The CBR was 56.5% and the DoCB was 18.4 months. The most frequently adverse events were injection site pain (10.3%) and musculoskeletal disorders (7.6%).

Conclusions

Fulvestrant 500 mg administered in clinical practice was shown to be effective (PFS, 10.6 months; CBR, 56.5%) and well tolerated, in accordance with previous trials.

Keywords

Metastatic breast cancer Postmenopausal women Hormone receptor-positive advanced breast cancer Fulvestrant 

Notes

Acknowledgements

We thank the participating patients and their families, all nurses and other members of the staff for their valuable contribution. We also appreciate Ana López-Ballesteros and Antonio Torres-Ruiz (Dynamic Science) for their medical-writing support and editorial assistance.

Compliance with ethical standards

Conflict of interest

JMBC participated as an advisor for AstraZeneca; IB, JSB and MRB (study coordinators) received honoraria from AstraZeneca. None of the other authors has declared any conflict of interest.

Ethical standards

The study was conducted in accordance with the 1964 Declaration of Helsinki and its later amendments. The study was approved by the Independent Research Ethics Committee at Hospital Universitario San Cecilio (Granada, Spain).

Informed consent

Informed consent was obtained from all individual participants before being included in the study.

Funding

The study described within the paper was sponsored by Astra Zeneca Spain S.A., Madrid, Spain.

References

  1. 1.
    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMedGoogle Scholar
  2. 2.
    Hashim D, Boffetta P, La Vecchia C, Rota M, Bertuccio P, Malvezzi M, Negri E. The global decrease in cancer mortality: trends and disparities. Ann Oncol. 2016;27(5):926–33.CrossRefPubMedGoogle Scholar
  3. 3.
    Dunnwald LK, Rossing MA, Li CI. Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res. 2007;9(1):R6.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Miller WR. Aromatase inhibitors: prediction of response and nature of resistance. Expert Opin Pharmacother. 2010;11(11):1873–87.CrossRefPubMedGoogle Scholar
  5. 5.
    Robertson JF. Fulvestrant (Faslodex)—how to make a good drug better. Oncologist. 2007;12(7):774–84.CrossRefPubMedGoogle Scholar
  6. 6.
    Howell A, Robertson JF, Quaresma AJ, 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(16):3396–403.CrossRefPubMedGoogle Scholar
  7. 7.
    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(16):3386–95.CrossRefPubMedGoogle Scholar
  8. 8.
    Howell A, Robertson JF, Abram P, Lichinitser MR, Elledge R, Bajetta E, et al. 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. 2004;22(9):1605–13.CrossRefPubMedGoogle Scholar
  9. 9.
    Di LA, 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(30):4594–600.CrossRefGoogle Scholar
  10. 10.
    Di LA, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, et al. Final overall survival: fulvestrant 500 mg vs 250 mg in the randomized CONFIRM trial. J Natl Cancer Inst. 2014;106(1):djt337.CrossRefGoogle Scholar
  11. 11.
    Summary of Product Characteristics. Faslodex 250 mg solution for injection. 2015. https://www.medicines.org.uk/emc/medicine/14381. Accessed 15 Mar 16.
  12. 12.
    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(27):4530–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Robertson JF, Lindemann JP, 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(2):503–11.CrossRefPubMedGoogle Scholar
  14. 14.
    Ellis MJ, Llombart-Cussac A, Feltl D, Dewar JA, Jasiowka 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(32):3781–7.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Migliaccio I, Malorni L, Hart CD, Guarducci C, Di LA. Endocrine therapy considerations in postmenopausal patients with hormone receptor positive, human epidermal growth factor receptor type 2 negative advanced breast cancers. BMC Med. 2015;13:46.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Iorfida M, Maiorano E, Orvieto E, Maisonneuve P, Bottiglieri L, Rotmensz N, et al. Invasive lobular breast cancer: subtypes and outcome. Breast Cancer Res Treat. 2012;133(2):713–23.CrossRefPubMedGoogle Scholar
  17. 17.
    Wasif N, Maggard MA, Ko CY, Giuliano AE. Invasive lobular vs. ductal breast cancer: a stage-matched comparison of outcomes. Ann Surg Oncol. 2010;17(7):1862–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Adachi Y, Ishiguro J, Kotani H, Hisada T, Ichikawa M, Gondo N, et al. Comparison of clinical outcomes between luminal invasive ductal carcinoma and luminal invasive lobular carcinoma. BMC Cancer. 2016;16(1):248.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.CrossRefPubMedGoogle Scholar
  20. 20.
    Prat A, Perou CM. Deconstructing the molecular portraits of breast cancer. Mol Oncol. 2011;5(1):5–23.CrossRefPubMedGoogle Scholar
  21. 21.
    Anderson WF, Chu KC, Chatterjee N, Brawley O, Brinton LA. Tumor variants by hormone receptor expression in white patients with node-negative breast cancer from the surveillance, epidemiology, and end results database. J Clin Oncol. 2001;19(1):18–27.CrossRefPubMedGoogle Scholar
  22. 22.
    Dowsett M, Allred C, Knox J, Quinn E, Salter J, Wale C, et al. Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the arimidex, tamoxifen, alone or in combination trial. J Clin Oncol. 2008;26(7):1059–65.CrossRefPubMedGoogle Scholar
  23. 23.
    Viale G, Regan MM, Maiorano E, Mastropasqua MG, Dell’Orto P, Rasmussen BB, et al. Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal early breast cancer: BIG 1-98. J Clin Oncol. 2007;25(25):3846–52.CrossRefPubMedGoogle Scholar
  24. 24.
    Inic Z, Zegarac M, Inic M, Markovic I, Kozomara Z, Djurisic I, et al. Difference between luminal A and luminal B subtypes according to Ki-67, tumor size, and progesterone receptor negativity providing prognostic information. Clin Med Insights Oncol. 2014;8:107–11.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Untch M, Gerber B, Harbeck N, Jackisch C, Marschner N, Mobus V, et al. 13th st. Gallen international breast cancer conference 2013: primary therapy of early breast cancer evidence, controversies, consensus—opinion of a german team of experts (zurich 2013). Breast Care (Basel). 2013;8(3):221–9.Google Scholar
  26. 26.
    Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009;27(33):5538–46.CrossRefPubMedGoogle Scholar
  27. 27.
    Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, et al. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009;27(33):5529–37.CrossRefPubMedGoogle Scholar
  28. 28.
    Mauriac L, Romieu G, Bines J. Activity of fulvestrant versus exemestane in advanced breast cancer patients with or without visceral metastases: data from the EFECT trial. Breast Cancer Res Treat. 2009;117(1):69–75.CrossRefPubMedGoogle Scholar
  29. 29.
    Clarke R, Tyson JJ, Dixon JM. Endocrine resistance in breast cancer–an overview and update. Mol Cell Endocrinol. 2015;418(Pt 3):220–34.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Vergote I, Amant F, Leunen K, Van GT, Berteloot P, Neven P. Metastatic breast cancer: sequencing hormonal therapy and positioning of fulvestrant. Int J Gynecol Cancer. 2006;16(Suppl 2):524–6.CrossRefPubMedGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2017

Authors and Affiliations

  • I. Blancas
    • 1
  • M. Fontanillas
    • 2
  • V. Conde
    • 3
  • J. Lao
    • 4
  • E. Martínez
    • 5
  • M. J. Sotelo
    • 6
  • A. Jaen
    • 7
  • J. L. Bayo
    • 8
  • F. Carabantes
    • 9
  • J. J. Illarramendi
    • 10
  • M. M. Gordon
    • 11
  • J. Cruz
    • 12
  • A. García-Palomo
    • 13
  • C. Mendiola
    • 14
  • E. Pérez-Ruiz
    • 15
  • J. S. Bofill
    • 16
  • J. M. Baena-Cañada
    • 17
  • N. M. Jáñez
    • 18
  • G. Esquerdo
    • 19
  • M. Ruiz-Borrego
    • 20
  1. 1.Hospital Universitario Clínico San Cecilio, Complejo Hospitalario UniversitarioGranadaSpain
  2. 2.Hospital Clinic de BarcelonaBarcelonaSpain
  3. 3.Hospital Universitario Virgen de las NievesGranadaSpain
  4. 4.Hospital Universitario Miguel ServetZaragozaSpain
  5. 5.Hospital Provincial de CastellónCastelló de la PlanaSpain
  6. 6.Hospital Universitario Clínico San CarlosMadridSpain
  7. 7.Hospital de JaénJaénSpain
  8. 8.Hospital Juan Ramón Jiménez, Ronda Exterior Norte s/nHuelvaSpain
  9. 9.Hospital Universitario Carlos HayaMálagaSpain
  10. 10.Complejo Universitario Hospital de NavarraPamplonaSpain
  11. 11.Hospital de JerezCádizSpain
  12. 12.Hospital Universitario de CanariasSanta Cruz de TenerifeSpain
  13. 13.Complejo Universitario Asistencial de LeónLeónSpain
  14. 14.Hospital UniversitarioMadridSpain
  15. 15.Hospital Costa del SolMarbellaSpain
  16. 16.Hospital Nuestra Señora De ValmeSevilleSpain
  17. 17.Hospital Universitario Puerta del MarCádizSpain
  18. 18.Hospital Ramón y CajalMadridSpain
  19. 19.Clínica BenidormBenidormSpain
  20. 20.Hospital Universitario Virgen del RocíoSevilleSpain

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