The purpose of the study is to compare how treatment with Fulvestrant (FASLODEX) or Anastrozole (ARIMIDEX) effects disease progression for women with locally advanced or metastatic breast cancer who have not had prior hormonal treatment.
A Randomised, Double-blind, Parallel-group, Multicentre, Phase III Study to Compare the Efficacy and Tolerability of Fulvestrant (FASLODEX) 500 mg with Anastrozole (ARIMIDEX) 1 mg as Hormonal Treatment for Postmenopausal Women with Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer Who Have Not Previously Been Treated With Any Hormonal Therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
462
2 x intramuscular injections at day 1, 14, 28 and every 28 days thereafter
oral tablet 1 daily
2 x intramuscular injections at day 1, 14, 28 and every 28 days thereafter
Comparison of Progression-Free Survival (PFS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole
PFS was defined as the time from randomisation until objective disease progression according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1), surgery or radiotherapy to manage worsening of disease or death by any cause (in the absence of progression). Outcome measure is reported as median time from randomisation to PFS, calculated using the Kaplan-Meier technique.
Time frame: Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until the earliest of disease progression evident, patient dies or has surgery/radiotherapy for their disease (up to approximately 38 months)
Comparison of Overall Survival (OS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole; Percentage of Patients With Events
OS was defined as the time from randomisation until death by any cause. The current OS data correspond to that of the final analysis and the outcome measure is reported as percentage of patients with events.
Time frame: Baseline (Day 0) up to data cut-off for final analysis (up to approximately 116 months). Following disease progression, patients were to be contacted at 12 weekly intervals to determine survival status
Objective Response Rate (ORR) for Fulvestrant Treatment Versus Anastrozole Treatment
ORR was defined as the percentage patients with an objective response (i.e. those recording a partial response \[PR\] or complete response \[CR\]) at some point during the study, prior to disease progression. ORR was assessed in patients with measurable disease at baseline only. The determination of measurable disease at baseline was done using baseline RECIST data. CR was disappearance of all target lesions since baseline; was any pathological lymph nodes selected as target lesions (TL) to have a reduction in short axis to \<10 millimeter. PR was at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
Time frame: Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
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oral tablet 1 daily
Research Site
Modesto, California, United States
Research Site
Savannah, Georgia, United States
Research Site
Auburn, Maine, United States
Research Site
Worcester, Massachusetts, United States
Research Site
Detroit, Michigan, United States
Research Site
St Louis, Missouri, United States
Research Site
Lincoln, Nebraska, United States
Research Site
Somerset, New Jersey, United States
Research Site
Columbus, Ohio, United States
Research Site
Montgomery, Ohio, United States
...and 108 more locations
Duration of Response (DoR) for Fulvestrant Treatment Versus Anastrozole Treatment
DoR was defined only for patients who had an objective response, as the time in days from date of first documentation of response (CR/PR) until date of disease progression. CR was disappearance of all target lesions since baseline; any pathological lymph nodes selected as TL to have a reduction in short axis to \<10 mm. At least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
Time frame: Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
Expected Duration of Response (EDoR) for Fulvestrant Treatment Versus Anastrozole Treatment
EDoR was estimated using the formula EDoR = p Efp(x), where x = DoR, p = proportion of responders, and Efp(x) = mean duration of response for responders. The estimation was completed by using the maximum likelihood estimates of p and Efp(x), as described by Ellis (Ellis S et al. Analysis of duration of response in oncology trials, Contemp Clin Trials 2008; 29:456-65).
Time frame: Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
Clinical Benefit Rate (CBR) for Fulvestrant Treatment Versus Anastrozole Treatment
CBR was defined as the percentage of patients who had a clinical benefit (i.e. best objective response of CR, PR or stable disease), that was maintained for at least 24 weeks, prior to any evidence of progression. Note that a minimum duration of 22 weeks for CBR was applicable in the analysis (rather than 24 weeks) to allow for the protocolled window of +/-2 weeks.
Time frame: Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
Duration of Clinical Benefit (DoCB) for Fulvestrant Treatment Versus Anastrozole Treatment
DoCB was defined only for patients who had clinical benefit, as the time in days from date of randomisation until the date of disease progression.
Time frame: Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
Expected Duration of Clinical Benefit (EDoCB) for Fulvestrant Treatment Versus Anastrozole Treatment
EDoCB was estimated using the formula EDoCB = p Efp(x), where x = EDoCB, p = proportion of responders, and Efp(x) = mean duration of response for responders. The estimation was completed by using the maximum likelihood estimates of p and Efp(x), as described by Ellis (Ellis S et al. Analysis of duration of response in oncology trials, Contemp Clin Trials 2008; 29:456-65).
Time frame: Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
Comparison of the Effect of Fulvestrant Treatment Versus Anastrozole Treatment on Time to Deterioration of Health-Related Quality of Life (HRQoL)
The Functional Assessment of Cancer Therapy - Breast (FACT-B) questionnaire was the instrument selected to assess HRQoL and comprised of following subscales: physical well-being (PWB), functional well-being (FWB), social well-being, emotional well-being, and breast cancer subscale (BCS). The main outcome measure from the FACT-B questionnaire was the Trial Outcome Index (TOI), which was a summary of the following subscales: PWB, FWB, and BCS. Outcome measure is reported as median time to deterioration, defined as the interval from the date of baseline of final analysis to the first assessment of worsened without an improvement in the next 12 weeks in FACT-B TOI, or the date of death (by any cause in the absence of symptom deterioration). Time to deterioration as measured by FACT-B total score was derived similarly and is also reported.
Time frame: Quality of life questionnaires administered at 3 months post objective disease progression, then at 6-monthly intervals (approximately 75 months)