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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

Abstract

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.

Keywords

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

Abbreviations

AE

Adverse event

AI

Aromatase inhibitor

CBR

Clinical benefit rate

CI

Confidence interval

CONFIRM

COmparisoN of Faslodex In Recurrent or Metastatic breast cancer

DoCB

Duration of clinical benefit

DoR

Duration of response

ER

Estrogen receptor

FINDER

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

FIRST

Fulvestrant fIRst-line Study comparing endocrine Treatments

HR

Hormone receptor

ORR

Objective response rate

NEWEST

Neoadjuvant Endocrine therapy for Women with Estrogen-Sensitive Tumors

PFS

Progression-free survival

PgR

Progesterone receptor

PK

Pharmacokinetic

RECIST

Response Evaluation in Solid Tumors

SAE

Serious adverse event

TTF

Time to treatment failure

TTP

Time to progression

WHO-PS

World Health Organization-Performance Status

Notes

Acknowledgments

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.

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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

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