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.
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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
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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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L. Emerson is a previous employee of AstraZeneca, Charnwood, UK.
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Robertson, J.F.R., Lindemann, J.P.O., Llombart-Cussac, A. 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 136, 503–511 (2012). https://doi.org/10.1007/s10549-012-2192-4
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DOI: https://doi.org/10.1007/s10549-012-2192-4