Breast Cancer Research and Treatment

, Volume 136, Issue 2, pp 503–511 | Cite as

Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: follow-up analysis from the randomized ‘FIRST’ study

  • John F. R. RobertsonEmail author
  • Justin P. O. Lindemann
  • Antonio Llombart-Cussac
  • Janusz Rolski
  • David Feltl
  • John Dewar
  • Laura Emerson
  • Andrew Dean
  • Matthew J. Ellis
Clinical Trial


Fulvestrant fIRst-line Study comparing endocrine Treatments is a phase II, randomized, open-label study comparing fulvestrant 500 mg with anastrozole 1 mg as first-line endocrine therapy for postmenopausal women with hormone receptor-positive (HR+) advanced breast cancer. At data cut-off, only 36 % of patients had progressed and the median time to progression (TTP) had not been reached for fulvestrant. Here, we report follow-up data for TTP for fulvestrant 500 mg versus anastrozole 1 mg. Key inclusion criteria were postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive locally advanced or metastatic breast cancer and no prior endocrine therapy. Key exclusion criteria were presence of life-threatening metastases and prior treatment with a non-approved drug. Fulvestrant was administered 500 mg/month plus 500 mg on day 14 of month 1; anastrozole was administered 1 mg/day. TTP was defined by modified Response Evaluation Criteria in Solid Tumors v1.0 before data cut-off for the primary analysis, and investigator opinion after data cut-off. Best overall response to subsequent therapy and serious adverse events are also reported. In total, 205 patients received fulvestrant 500 mg (n = 102) or anastrozole (n = 103). Follow-up analysis was performed when 79.5 % of patients had discontinued study treatment. Median TTP was 23.4 months for fulvestrant versus 13.1 months for anastrozole; a 34 % reduction in risk of progression (hazard ratio 0.66; 95 % confidence interval: 0.47, 0.92; P = 0.01). Best overall response to subsequent therapy and clinical benefit rate for subsequent endocrine therapy was similar between the treatment groups. No new safety concerns for fulvestrant 500 mg were documented. These longer-term, follow-up results confirm efficacy benefit for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for HR+ advanced breast cancer in terms of TTP, and, importantly, show similar best overall response rates to subsequent endocrine therapy.


Advanced breast cancer Anastrozole Fulvestrant 500 mg Hormone receptor-positive Time to progression 



Adverse event


Aromatase inhibitor


Clinical benefit rate


Confidence interval


COmparisoN of Faslodex In Recurrent or Metastatic breast cancer


Duration of clinical benefit


Duration of response


Estrogen receptor


Faslodex InvestigatioN of Dose evaluation in Estrogen Receptor-positive advanced breast cancer (FINDER)


Fulvestrant fIRst-line Study comparing endocrine Treatments


Hormone receptor


Objective response rate


Neoadjuvant Endocrine therapy for Women with Estrogen-Sensitive Tumors


Progression-free survival


Progesterone receptor




Response Evaluation in Solid Tumors


Serious adverse event


Time to treatment failure


Time to progression


World Health Organization-Performance Status



This study was funded by AstraZeneca. We thank Simon Vass PhD, from Complete Medical Communications, who provided medical writing support, funded by AstraZeneca.

Conflict of interest

John F. R. Robertson has received consultancy, honoraria, and speaker fees as well as research funding from AstraZeneca. Antonio Llombart-Cussac has received consultancy fees from AstraZeneca. Janusz Rolski has no conflicts of interest to declare. David Feltl and John Dewar have received research funding from AstraZeneca. Matthew J. Ellis is a Bioclassifier employee and shareholder and has received consultancy fees and research funding from AstraZeneca, Novartis, and Pfizer. Justin P. O. Lindemann and Andrew Dean are AstraZeneca employees and shareholders. Laura Emerson is a former AstraZeneca employee.

Ethical standards

The study was performed in accordance with the Declaration of Helsinki and was consistent with International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice. The study protocol, patient consent forms, and information sheets were approved by the relevant independent ethics committees and institutional review boards.


  1. 1.
    Bonneterre J, Buzdar A, Nabholtz JM, Robertson JF, Thürlimann B, von Euler M, Sahmoud T, Webster A, Steinberg M, Arimidex Writing Committee Investigators Committee Members (2001) Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer 92:2247–2258PubMedCrossRefGoogle Scholar
  2. 2.
    Bonneterre J, Thürlimann B, Robertson JF, Krzakowski M, Mauriac L, Koralewski P, Vergote I, Webster A, Steinberg M, von Euler M (2000) Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. J Clin Oncol 18:3748–3757PubMedGoogle Scholar
  3. 3.
    Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, Verhoeven D, Pedrini JL, Smirnova I, Lichinitser MR, Pendergrass K, Garnett S, Lindemann JP, Sapunar F, Martin M (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 28:4594–4600PubMedCrossRefGoogle Scholar
  4. 4.
    Howell A, Robertson JFR, Abram P, Lichinitser MR, Elledge R, Bajetta E, Watanabe T, Morris C, Webster A, Dimery I, Osborne CK (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 22:1605–1613PubMedCrossRefGoogle Scholar
  5. 5.
    Howell A, Robertson JFR, Quaresma Albano J, Aschermannova A, Mauriac L, Kleeberg UR, Vergote I, Erikstein B, Webster A, Morris C (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 20:3396–3403PubMedCrossRefGoogle Scholar
  6. 6.
    Howell A, Sapunar F (2011) Fulvestrant revisited: efficacy and safety of the 500-mg dose. Clin Breast Cancer 11:204–210PubMedCrossRefGoogle Scholar
  7. 7.
    Kuter I, Hegg R, Singer CF, Badwe R, Lowe E, on behalf of the NEWEST investigators (2007) Fulvestrant 500 mg vs 250 mg: first results from NEWEST, a randomized, phase II neoadjuvant trial in postmenopausal women with locally advanced, estrogen receptor-positive breast cancer. Breast Cancer Res Treat 106: S7 (abstract 23)Google Scholar
  8. 8.
    Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Jaenicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Chaudri-Ross H, Lang R, Wyld P, Bhatnagar A (2003) Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol 21:2101–2109PubMedCrossRefGoogle Scholar
  9. 9.
    Nabholtz JM, Buzdar A, Pollak M, Harwin W, Burton G, Mangalik A, Steinberg M, Webster A, von Euler M (2000) Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. J Clin Oncol 18:3758–3767PubMedGoogle Scholar
  10. 10.
    Ohno S, Rai Y, Iwata H, Yamamoto N, Yoshida M, Iwase H, Masuda N, Nakamura S, Taniguchi H, Kamigaki S, Noguchi S (2010) 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 21:2342–2347PubMedCrossRefGoogle Scholar
  11. 11.
    Osborne CK, Pippen J, Jones SE, Parker LM, Ellis M, Come S, Gertler SZ, May JT, Burton G, Dimery I, Webster A, Morris C, Elledge R, Buzdar A (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 20:3386–3395PubMedCrossRefGoogle Scholar
  12. 12.
    Paridaens RJ, Dirix LY, Beex LV, Nooij M, Cameron DA, Cufer T, Piccart MJ, Bogaerts J, Therasse P (2008) Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. J Clin Oncol 26:4883–4890PubMedCrossRefGoogle Scholar
  13. 13.
    Pritchard KI, Rolski J, Papai Z, Mauriac L, Cardoso F, Chang J, Panasci L, Ianuli C, Kahan Z, Fukase K, Lindemann JPO, Macpherson MP, Neven P (2010) Results of a phase II study comparing three dosing regimens of fulvestrant in postmenopausal women with advanced breast cancer (FINDER2). Breast Cancer Res Treat 123:453–461PubMedCrossRefGoogle Scholar
  14. 14.
    Robertson JF, Erikstein B, Osborne KC, Pippen J, Come SE, Parker LM, Gertler S, Harrison MP, Clarke DA (2004) Pharmacokinetic profile of intramuscular fulvestrant in advanced breast cancer. Clin Pharmacokinet 43:529–538PubMedCrossRefGoogle Scholar
  15. 15.
    Robertson JF, Nicholson RI, Bundred NJ, Anderson E, Rayter Z, Dowsett M, Fox JN, Gee JM, Webster A, Wakeling AE, Morris C, Dixon M (2001) Comparison of the short-term biological effects of 7alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5,(10)-triene-3,17beta-diol (Faslodex) versus tamoxifen in postmenopausal women with primary breast cancer. Cancer Res 61:6739–6746PubMedGoogle Scholar
  16. 16.
    Robertson JF, Osborne CK, Howell A, Jones SE, Mauriac L, Ellis M, Kleeberg UR, Come SE, Vergote I, Gertler S, Buzdar A, Webster A, Morris C (2003) Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials. Cancer 98:229–238PubMedCrossRefGoogle Scholar
  17. 17.
    Robertson JFR (2007) Fulvestrant (Faslodex)—how to make a good drug better. Oncologist 12:774–784PubMedCrossRefGoogle Scholar
  18. 18.
    Robertson JFR, Howell A, Gorbunova VA, Watanabe T, Pienkowski T, Lichinitser MR (2005) Sensitivity to further endocrine therapy is retained following progression on first-line fulvestrant. Breast Cancer Res Treat 92:169–174PubMedCrossRefGoogle Scholar
  19. 19.
    Robertson JFR, Llombart A, Rolski J, Feltl D, Dewar J, Macpherson E, Lindemann J, Ellis MJ (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 27:4530–4535PubMedCrossRefGoogle Scholar
  20. 20.
    Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (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 92:205–216PubMedCrossRefGoogle Scholar
  21. 21.
    Wakeling AE, Dukes M, Bowler J (1991) A potent specific pure antiestrogen with clinical potential. Cancer Res 51:3867–3873PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • John F. R. Robertson
    • 1
    Email author
  • Justin P. O. Lindemann
    • 2
  • Antonio Llombart-Cussac
    • 3
  • Janusz Rolski
    • 4
  • David Feltl
    • 5
  • John Dewar
    • 6
  • Laura Emerson
    • 7
  • Andrew Dean
    • 2
  • Matthew J. Ellis
    • 8
  1. 1.Division of Breast Surgery, Graduate Entry Medicine & Health School (GEMS)University of Nottingham, Royal Derby HospitalDerbyUK
  2. 2.AstraZenecaMacclesfieldUK
  3. 3.Hospital Arnau de VilanovaLéridaSpain
  4. 4.Centrum OnkologiiInstytut im M. Skłodowskiej-CurieKrakówPoland
  5. 5.FNsP OstravaRadioterapeutická klinikaOstrava-PorubaCzech Republic
  6. 6.Department of OncologyNinewells Hospital and Medical SchoolDundeeUK
  7. 7.AstraZenecaCharnwoodUK
  8. 8.Washington University School of MedicineSt LouisUSA

Personalised recommendations