Originally published as JCO Early Release 10.1200/JCO.2008.21.1136 on August 24 2009

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Activity of Fulvestrant 500 mg Versus Anastrozole 1 mg As First-Line Treatment for Advanced Breast Cancer: Results From the FIRST Study

From the Division of Breast Surgery, University of Nottingham, Nottingham; Department of Oncology, Ninewells Hospital and Medical School, Dundee; AstraZeneca Pharmaceuticals, Alderley Park, United Kingdom; Hospital Arnau de Vilanova, Lérida, Spain; Centrum Onkologii, Instytut im M. Skodowskiej-Curie, Krakow, Poland; Fackultni Nemocnice Ostrava, Radioterapeutická klinika, Ostrava-Poruba, Czech Republic; Washington University School of Medicine, St Louis, MO.

Corresponding author: John F.R. Robertson, MD, Division of Breast Surgery, University of Nottingham, Nottingham City Hospital, Hucknall Rd, Nottingham, NG5 1PB, United Kingdom; e-mail: john.robertson{at}nottingham.ac.uk.

Purpose To compare the clinical activity of the pure antiestrogen fulvestrant at 500 mg/mo (double the approved dose) with the aromatase inhibitor anastrozole as first-line endocrine therapy for advanced hormone receptor–positive breast cancer in postmenopausal women.

Patients and Methods FIRST (Fulvestrant First-Line Study Comparing Endocrine Treatments) is a phase II, randomized, open-label, multicenter study of a fulvestrant high-dose (HD) regimen (500 mg/mo plus 500 mg on day 14 of month 1) versus anastrozole (1 mg/d). The primary efficacy end point was clinical benefit rate (CBR), defined as the proportion of patients experiencing an objective response (OR) or stable disease for 24 weeks. The primary analysis was performed 6 months after the last patient was randomly assigned.

Results CBR was similar for fulvestrant HD (n = 102) and anastrozole (n = 103), 72.5% v 67.0%, respectively (odds ratio, 1.30; 95% CI, 0.72 to 2.38; P = .386). Objective response rate (ORR) was also similar between treatments: fulvestrant HD, 36.0%; anastrozole, 35.5%. Time to progression (TTP) was significantly longer for fulvestrant versus anastrozole (median TTP not reached for fulvestrant HD v 12.5 months for anastrozole; hazard ratio, 0.63; 95% CI, 0.39 to 1.00; P = .0496). Duration of OR and CB also numerically favored fulvestrant HD. Both treatments were well tolerated, with no significant differences in the incidence of prespecified adverse events.

Conclusion First-line fulvestrant HD was at least as effective as anastrozole for CBR and ORR and was associated with significantly longer TTP. Fulvestrant HD was generally well tolerated, with a safety profile similar to that of anastrozole.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00274469 [ClinicalTrials.gov] .

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