Breast Cancer Research and Treatment

, Volume 136, Issue 2, pp 503–511

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

DOI: 10.1007/s10549-012-2192-4

Cite this article as:
Robertson, J.F.R., Lindemann, J.P.O., Llombart-Cussac, A. et al. Breast Cancer Res Treat (2012) 136: 503. doi:10.1007/s10549-012-2192-4


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

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • John F. R. Robertson
    • 1
  • 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