Abstract OT3-2-09: FALCON: A randomised, double-blind, multicentre, phase III study comparing fulvestrant 500 mg with anastrozole 1 mg for postmenopausal women with hormone receptor-positive locally advanced or metastatic breast cancer who have not previously been treated with any hormonal therapy
Authors: Ellis MJ , Prahladan M , Green NL , Mari E , Robertson JFR 
Published: August 2014

Background: The Phase III CONFIRM study demonstrated that a higher dose (500 mg) of fulvestrant, an estrogen receptor (ER) antagonist for treatment of advanced breast cancer, was associated with a significant increase in progression-free survival (PFS) without increased toxicity versus fulvestrant 250 mg.Moreover, a Phase II study (FIRST) showed that first-line treatment with fulvestrant 500 mg was at least as effective as anastrozole 1 mg with a similar safety profile. The aim of the FALCON study is to investigate whether fulvestrant 500 mg is superior to anastrozole 1 mg as first-line endocrine therapy. FALCON is the only Phase III study in recent years to compare two endocrine therapies as first-line treatment in metastatic breast cancer (MBC); hence, results may potentially affect standard clinical practice in the future.

Trial design: This is a randomised, double-blind, double-dummy, international, multicentre study comparing efficacy and tolerability of fulvestrant with anastrozole (NCT01602380). Eligible patients are randomised 1:1 to receive fulvestrant 500 mg or anastrozole 1 mg, and stratified at randomisation based on whether (1) they have locally advanced or MBC (2) they have received prior chemotherapy for locally advanced or MBC or not and (3) they have measurable or non-measurable disease.

Eligibility criteria: Eligible are postmenopausal women with histologically confirmed, ER-positive, locally advanced or MBC who have not previously received any endocrine therapy. Patients may have received one line of cytotoxic chemotherapy but must show progressive disease prior to enrolment, have a World Health Organisation performance status of 0, 1 or 2 and at least one lesion that can be accurately assessed at baseline and is suitable for repeated assessment according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1) guidelines.

Specific aims: The primary objective is to demonstrate the superior PFS of patients treated with fulvestrant 500 mg versus patients treated with anastrozole 1 mg. Secondary objectives include comparison of the overall survival (OS), the objective response rate (ORR), the clinical benefit rate (CBR) and quality of life (QoL) between the treatment groups, as well as safety and tolerability assessments.

Statistical methods: Comparison of PFS and OS for fulvestrant 500 mg versus anastrozole 1 mg will be performed using a stratified log-rank test. A multiple testing procedure will be used to control the overall type 1 error rate at 2.5% (1-sided). Results will be presented as an estimated hazard ratio, associated confidence interval and p-value. ORR and CBR will be analysed using a logistic regression model and examination of the odds ratio of the 2 treatment groups. A time to deterioration analysis will be performed for QoL endpoints.

Present accrual and target accrual: Recruitment is currently ongoing; on June 6, 2013, 101 patients had been randomised. The recruitment target is 450 patients; 124 study sites worldwide are currently initiated.

Contact information: Please contact the authors for specific information about this study.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-2-09.