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    Clinical Trial Results:
    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 (FALCON)

    Summary
    EudraCT number
    		 2011-006326-24
    Trial protocol
    		 GB   ES   CZ   SK   IT   PL  
    Global end of trial date
    16 Jan 2026

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 Apr 2026
    First version publication date
    30 Apr 2026
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D699BC00001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01602380
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca AB
    Sponsor organisation address
    Karlebyhusentren, B674 Astraallen, Södertälje, Sweden, 151 85
    Public contact
    Global Clinical Lead, AstraZeneca, +1 877-240-9479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca, +1 877-240-9479, information.center@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    16 Jan 2026
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Jan 2026
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to demonstrate the superior progression-free survival (PFS) of patients treated with fulvestrant 500 milligram (mg) versus patients treated with anastrozole 1 mg.
    Protection of trial subjects
    This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Council for Harmonisation/Good Clinical Practice, applicable regulatory requirements, and the AstraZeneca policy on Bioethics.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    17 Oct 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 12
    Country: Number of subjects enrolled
    Brazil: 7
    Country: Number of subjects enrolled
    Canada: 29
    Country: Number of subjects enrolled
    China: 25
    Country: Number of subjects enrolled
    Czechia: 7
    Country: Number of subjects enrolled
    Italy: 15
    Country: Number of subjects enrolled
    Japan: 31
    Country: Number of subjects enrolled
    Mexico: 19
    Country: Number of subjects enrolled
    Peru: 23
    Country: Number of subjects enrolled
    Poland: 9
    Country: Number of subjects enrolled
    Romania: 8
    Country: Number of subjects enrolled
    Russian Federation: 102
    Country: Number of subjects enrolled
    Slovakia: 6
    Country: Number of subjects enrolled
    South Africa: 16
    Country: Number of subjects enrolled
    Spain: 19
    Country: Number of subjects enrolled
    Taiwan: 11
    Country: Number of subjects enrolled
    Türkiye: 1
    Country: Number of subjects enrolled
    Ukraine: 85
    Country: Number of subjects enrolled
    United Kingdom: 17
    Country: Number of subjects enrolled
    United States: 20
    Worldwide total number of subjects
    462
    EEA total number of subjects
    64
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    263
    From 65 to 84 years
    189
    85 years and over
    10

    Subject disposition

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    Recruitment
    Recruitment details
    		 First patient enrolled: 17 October 2012.

    Pre-assignment
    Screening details
    		 524 patients were enrolled (signed informed consent). Patients were assigned to treatment if they met all inclusion and none of the exclusion criteria. 62 patients were not randomised, mainly due to eligibility criteria not being fulfilled (44/62 patients) or patient decision (13/62 patients). 462 patients were randomised to receive treatment.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Fulvestrant 500 mg
    Arm description
    		 Patients received fulvestrant (Faslodex™) 500 mg, administered as two 5 milliliters (mL) intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo to match anastrozole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matching placebo was administered orally as a single daily tablet at a dose of 1 mg/day from randomisation on Day 0 until the patient permanently discontinued the treatment.

    Investigational medicinal product name
    Fulvestrant
    Investigational medicinal product code
    Other name
    Faslodex
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Fulvestrant 500 mg was administered as two 5 ml intramuscular injections, one in each buttock, on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter until the patient permanently discontinued the treatment.

    Arm title
    		 Anastrozole 1 mg
    Arm description
    		 Patients received anastrozole (Arimidex™), administered orally as a single tablet at a dose of 1 mg/day from randomisation on Day 0 and once daily thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive anastrozole also received placebo to match the fulvestrant schedule (injections on Days 0, 14 [±3], 28 [±3] and every 28 [±3] days thereafter).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Placebo to match fulvestrant
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Matching placebo was administered as two 5 mL intramuscular injections, one in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter until the patient permanently discontinued the treatment.

    Investigational medicinal product name
    Anastrozole
    Investigational medicinal product code
    Other name
    Arimidex
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Anastrozole was administered as a 1 mg oral tablet from randomisation on Day 0 until the patient permanently discontinued the treatment.

    Number of subjects in period 1
    		Fulvestrant 500 mg Anastrozole 1 mg
    Started
    230
    232
    Completed
    25
    31
    Not completed
    205
    201
         Consent withdrawn by subject
    39
    41
         Eligibility criteria not fulfilled
    2
    3
         Death
    147
    145
         Unspecified
    2
    -
         Lost to follow-up
    15
    12

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Fulvestrant 500 mg
    Reporting group description
    		 Patients received fulvestrant (Faslodex™) 500 mg, administered as two 5 milliliters (mL) intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).

    Reporting group title
    Anastrozole 1 mg
    Reporting group description
    		 Patients received anastrozole (Arimidex™), administered orally as a single tablet at a dose of 1 mg/day from randomisation on Day 0 and once daily thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive anastrozole also received placebo to match the fulvestrant schedule (injections on Days 0, 14 [±3], 28 [±3] and every 28 [±3] days thereafter).

    Reporting group values
    		 Fulvestrant 500 mg Anastrozole 1 mg Total
    Number of subjects
    		 230 232 462
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 63.8 ( 9.86 ) 63.3 ( 10.38 ) -
    Sex: Female, Male
    Units:
        Female
    		 230 232 462
        Male
    		 0 0 0
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 1 5 6
        Asian
    		 36 34 70
        Black or African American
    		 4 4 8
        White
    		 175 174 349
        Other
    		 14 15 29

    End points

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    End points reporting groups
    Reporting group title
    Fulvestrant 500 mg
    Reporting group description
    		 Patients received fulvestrant (Faslodex™) 500 mg, administered as two 5 milliliters (mL) intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).

    Reporting group title
    Anastrozole 1 mg
    Reporting group description
    		 Patients received anastrozole (Arimidex™), administered orally as a single tablet at a dose of 1 mg/day from randomisation on Day 0 and once daily thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive anastrozole also received placebo to match the fulvestrant schedule (injections on Days 0, 14 [±3], 28 [±3] and every 28 [±3] days thereafter).

    Primary: Comparison of PFS in Patients Treated With Fulvestrant With Those Treated With Anastrozole

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    End point title
    		 Comparison of PFS in Patients Treated With Fulvestrant With Those Treated With Anastrozole
    End point description
    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. The intention to treat (ITT) analysis set included all randomised patients.
    End point type
    Primary
    End point timeframe
    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)
    End point values
    		 Fulvestrant 500 mg Anastrozole 1 mg
    Number of subjects analysed
    230
    232
    Units: Months
        median (confidence interval 95%)
    16.6 (13.83 to 20.99)
    13.8 (11.99 to 16.59)
    Statistical analysis title
    		 Comparison of PFS
    Statistical analysis description
    If the true PFS hazard ratio (HR) for comparison of fulvestrant vs. anastrozole was 0.69 (likely to correspond to a 45% prolongation of PFS) the study had 90% power to demonstrate a statistically significant difference for PFS with a one-sided type 1 error of 2.5% (two-sided 5%).
    Comparison groups
    Anastrozole 1 mg v Fulvestrant 500 mg
    Number of subjects included in analysis
    462
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.0486 [2]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.797
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.637
         upper limit
    		 0.999
    Notes
    [1] - Stratified log-rank test with factors for prior chemotherapy for locally advanced or metastatic disease and measurable disease at baseline. A hazard ratio < 1 favours fulvestrant.
    [2] - 2-sided p-value

    Secondary: Comparison of Overall Survival (OS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole; Percentage of Patients With Events

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    End point title
    		 Comparison of Overall Survival (OS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole; Percentage of Patients With Events
    End point description
    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. The ITT analysis set included all randomised patients. Date of death of 2 patients were unknown in the Anastrozole 1 mg arm, hence they were censored for OS analysis.
    End point type
    Secondary
    End point timeframe
    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
    End point values
    		 Fulvestrant 500 mg Anastrozole 1 mg
    Number of subjects analysed
    230
    232
    Units: Percentage of patients
        number (not applicable)
    68.3
    67.7
    Statistical analysis title
    		 Comparison of OS
    Statistical analysis description
    65% OS maturity
    Comparison groups
    Fulvestrant 500 mg v Anastrozole 1 mg
    Number of subjects included in analysis
    462
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.7579 [4]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.966
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.773
         upper limit
    		 1.206
    Notes
    [3] - Stratified log-rank test with factors for prior chemotherapy for locally advanced or metastatic disease and measurable disease at baseline. A HR of <1 favours fulvestrant.
    [4] - 2-sided p-value

    Secondary: Objective Response Rate (ORR) for Fulvestrant Treatment Versus Anastrozole Treatment

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    End point title
    		 Objective Response Rate (ORR) for Fulvestrant Treatment Versus Anastrozole Treatment
    End point description
    ORR was defined as the percentage of patients with an objective response (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. Percentages for ORR were calculated based on the number of patients in the ITT analysis set (which included all randomised patients) who had measurable disease at baseline (n=193 for Fulvestrant arm and n=196 for Anastrozole arm).
    End point type
    Secondary
    End point timeframe
    Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
    End point values
    		 Fulvestrant 500 mg Anastrozole 1 mg
    Number of subjects analysed
    193
    196
    Units: Percentage of patients
        number (not applicable)
    46.1
    44.9
    Statistical analysis title
    		 ORR
    Comparison groups
    Fulvestrant 500 mg v Anastrozole 1 mg
    Number of subjects included in analysis
    389
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.729 [5]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.074
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.716
         upper limit
    		 1.614
    Notes
    [5] - 2-sided p-value

    Secondary: Duration of Response (DoR) for Fulvestrant Treatment Versus Anastrozole Treatment

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    End point title
    		 Duration of Response (DoR) for Fulvestrant Treatment Versus Anastrozole Treatment
    End point description
    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. Only patients in the ITT analysis set (which included all randomised patients), who also had an objective response and had measurable disease at baseline were included in the DoR analysis (n=89 for Fulvestrant arm and n=88 for Anastrozole arm). 99999=75th percentile value not calculable due to insufficient data.
    End point type
    Secondary
    End point timeframe
    Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
    End point values
    		 Fulvestrant 500 mg Anastrozole 1 mg
    Number of subjects analysed
    89
    88
    Units: Months
        median (inter-quartile range (Q1-Q3))
    20.0 (10.6 to 99999)
    13.2 (8.3 to 24.7)
    No statistical analyses for this end point

    Secondary: Expected Duration of Response (EDoR) for Fulvestrant Treatment Versus Anastrozole Treatment

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    End point title
    		 Expected Duration of Response (EDoR) for Fulvestrant Treatment Versus Anastrozole Treatment
    End point description
    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). EDoR analysis was based on the number of patients in the ITT analysis set (which included all randomised patients) who had measurable disease at baseline (n=193 for Fulvestrant arm and n=196 for Anastrozole arm).
    End point type
    Secondary
    End point timeframe
    Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
    End point values
    		 Fulvestrant 500 mg Anastrozole 1 mg
    Number of subjects analysed
    193
    196
    Units: Days
        number (not applicable)
    346.84
    227.58
    Statistical analysis title
    		 EDoR
    Comparison groups
    Fulvestrant 500 mg v Anastrozole 1 mg
    Number of subjects included in analysis
    389
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0367 [6]
    Method
    		 Method of Ellis et al
    Parameter type
    		 Rato of EDoR
    Point estimate
    1.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.03
         upper limit
    		 2.26
    Notes
    [6] - 2-sided p-value

    Secondary: Clinical Benefit Rate (CBR) for Fulvestrant Treatment Versus Anastrozole Treatment

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    End point title
    		 Clinical Benefit Rate (CBR) for Fulvestrant Treatment Versus Anastrozole Treatment
    End point description
    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. The ITT analysis set included all randomised patients.
    End point type
    Secondary
    End point timeframe
    Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
    End point values
    		 Fulvestrant 500 mg Anastrozole 1 mg
    Number of subjects analysed
    230
    232
    Units: Percentage of patients
        number (not applicable)
    78.3
    74.1
    Statistical analysis title
    		 CBR
    Comparison groups
    Fulvestrant 500 mg v Anastrozole 1 mg
    Number of subjects included in analysis
    462
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3045 [7]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.253
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.815
         upper limit
    		 1.932
    Notes
    [7] - 2-sided p-value

    Secondary: Duration of Clinical Benefit (DoCB) for Fulvestrant Treatment Versus Anastrozole Treatment

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    End point title
    		 Duration of Clinical Benefit (DoCB) for Fulvestrant Treatment Versus Anastrozole Treatment
    End point description
    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. Only patients in the ITT analysis set (which included all randomised patients) who also had a clinical benefit were included in the DoCB analysis (n=180 for Fulvestrant arm and n=172 for Anastrozole arm). 99999=75th percentile value not calculable due to insufficient data.
    End point type
    Secondary
    End point timeframe
    Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
    End point values
    		 Fulvestrant 500 mg Anastrozole 1 mg
    Number of subjects analysed
    180
    172
    Units: Months
        median (inter-quartile range (Q1-Q3))
    22.1 (11.2 to 99999)
    19.1 (11.3 to 30.4)
    No statistical analyses for this end point

    Secondary: Expected Duration of Clinical Benefit (EDoCB) for Fulvestrant Treatment Versus Anastrozole Treatment

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    End point title
    		 Expected Duration of Clinical Benefit (EDoCB) for Fulvestrant Treatment Versus Anastrozole Treatment
    End point description
    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). The ITT analysis set included all randomised patients.
    End point type
    Secondary
    End point timeframe
    Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)
    End point values
    		 Fulvestrant 500 mg Anastrozole 1 mg
    Number of subjects analysed
    230
    232
    Units: Days
        number (not applicable)
    667.94
    532.04
    Statistical analysis title
    		 EDoCB
    Comparison groups
    Fulvestrant 500 mg v Anastrozole 1 mg
    Number of subjects included in analysis
    462
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0561 [8]
    Method
    		 Method of Ellis et al
    Parameter type
    		 Ratio of EDoCB
    Point estimate
    1.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.99
         upper limit
    		 1.59
    Notes
    [8] - 2-sided p-value

    Secondary: Comparison of the Effect of Fulvestrant Treatment Versus Anastrozole Treatment on Time to Deterioration of Health-Related Quality of Life (HRQoL)

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    End point title
    		 Comparison of the Effect of Fulvestrant Treatment Versus Anastrozole Treatment on Time to Deterioration of Health-Related Quality of Life (HRQoL)
    End point description
    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. The ITT analysis set included all randomised patients.
    End point type
    Secondary
    End point timeframe
    Quality of life questionnaires administered at 3 months post objective disease progression, then at 6-monthly intervals (approximately 75 months)
    End point values
    		 Fulvestrant 500 mg Anastrozole 1 mg
    Number of subjects analysed
    230
    232
    Units: months
    median (inter-quartile range (Q1-Q3))
        Time to TOI deterioration
    14.1 (5.5 to 44.1)
    11.1 (5.5 to 38.3)
        Time to FACT-B total score deterioration
    13.8 (5.5 to 38.7)
    11.1 (4.8 to 33.6)
    Statistical analysis title
    		 Comparison of the effect on HRQoL
    Statistical analysis description
    Comparative statistical analysis for time to deterioration of FACT-B total score is presented (fulvestrant versus anastrozole).
    Comparison groups
    Fulvestrant 500 mg v Anastrozole 1 mg
    Number of subjects included in analysis
    462
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 = 0.0844 [10]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 1.03
    Notes
    [9] - Stratified log-rank test with factors for prior chemotherapy for locally advanced/metastatic disease and measurable/non-measurable disease at baseline. A hazard ratio < 1 favours fulvestrant.
    [10] - 2-sided p-value
    Statistical analysis title
    		 Comparison of the effect on HRQoL
    Statistical analysis description
    Comparative statistical analysis for time to deterioration of TOI score is presented (fulvestrant versus anastrozole).
    Comparison groups
    Fulvestrant 500 mg v Anastrozole 1 mg
    Number of subjects included in analysis
    462
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [11]
    P-value
    		 = 0.2846 [12]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1.11
    Notes
    [11] - Stratified log-rank test with factors for prior chemotherapy for locally advanced/metastatic disease and measurable/non-measurable disease at baseline. A hazard ratio < 1 favours fulvestrant.
    [12] - 2-sided p-value

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    116 months (duration from first patient enrolled to data cut-off date for the final analysis)
    Adverse event reporting additional description
    All-Cause Mortality: The ITT analysis set: All randomised patients. Serious adverse events and other (non-serious) adverse events: Safety population was defined as all patients who received at least 1 dose of randomised study medication. 2 patients in the Fulvestrant 500 mg arm did not receive treatment and were not included in safety population.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Fulvestrant 500 mg
    Reporting group description
    		 Patients received fulvestrant (Faslodex™) 500 mg, administered as two 5 mL intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).

    Reporting group title
    Anastrozole 1 mg
    Reporting group description
    		 Patients received anastrozole (Arimidex™), administered orally as a single tablet at a dose of 1 mg/day from randomisation on Day 0 and once daily thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive anastrozole also received placebo to match the fulvestrant schedule (injections on Days 0, 14 [±3], 28 [±3] and every 28 [±3] days thereafter).

    Serious adverse events
    		 Fulvestrant 500 mg Anastrozole 1 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    39 / 228 (17.11%)
    36 / 232 (15.52%)
         number of deaths (all causes)
    157
    159
         number of deaths resulting from adverse events
    7
    9
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colorectal cancer
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 228 (0.44%)
    3 / 232 (1.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 228 (0.44%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acoustic neuroma
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of the oral cavity
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertensive crisis
         subjects affected / exposed
    2 / 228 (0.88%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 228 (0.00%)
    2 / 232 (0.86%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchiectasis
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    3 / 228 (1.32%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pleural effusion
         subjects affected / exposed
    7 / 228 (3.07%)
    2 / 232 (0.86%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 228 (0.88%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Skin abrasion
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    2 / 228 (0.88%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic spinal cord compression
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure acute
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Atrial flutter
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Angina pectoris
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 228 (0.44%)
    2 / 232 (0.86%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    0 / 228 (0.00%)
    3 / 232 (1.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Palpitations
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Haemorrhagic stroke
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    2 / 228 (0.88%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 228 (0.44%)
    2 / 232 (0.86%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia macrocytic
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Dysphagia
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal dilatation
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal stenosis
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 228 (0.00%)
    2 / 232 (0.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Musculoskeletal and connective tissue disorders
    Neck pain
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 228 (0.00%)
    2 / 232 (0.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Device related sepsis
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 228 (0.44%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    2 / 228 (0.88%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 228 (1.32%)
    4 / 232 (1.72%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 228 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 228 (0.88%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 228 (0.44%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 228 (0.00%)
    2 / 232 (0.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Fulvestrant 500 mg Anastrozole 1 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    166 / 228 (72.81%)
    171 / 232 (73.71%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    16 / 228 (7.02%)
    8 / 232 (3.45%)
         occurrences all number
    18
    8
    Aspartate aminotransferase increased
         subjects affected / exposed
    12 / 228 (5.26%)
    9 / 232 (3.88%)
         occurrences all number
    13
    9
    Vascular disorders
    Hypertension
         subjects affected / exposed
    18 / 228 (7.89%)
    22 / 232 (9.48%)
         occurrences all number
    19
    25
    Hot flush
         subjects affected / exposed
    26 / 228 (11.40%)
    24 / 232 (10.34%)
         occurrences all number
    35
    32
    Nervous system disorders
    Headache
         subjects affected / exposed
    12 / 228 (5.26%)
    12 / 232 (5.17%)
         occurrences all number
    13
    12
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    9 / 228 (3.95%)
    20 / 232 (8.62%)
         occurrences all number
    10
    21
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    29 / 228 (12.72%)
    18 / 232 (7.76%)
         occurrences all number
    35
    20
    Injection site pain
         subjects affected / exposed
    12 / 228 (5.26%)
    10 / 232 (4.31%)
         occurrences all number
    15
    23
    Oedema peripheral
         subjects affected / exposed
    11 / 228 (4.82%)
    14 / 232 (6.03%)
         occurrences all number
    11
    15
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    16 / 228 (7.02%)
    11 / 232 (4.74%)
         occurrences all number
    16
    13
    Diarrhoea
         subjects affected / exposed
    15 / 228 (6.58%)
    15 / 232 (6.47%)
         occurrences all number
    20
    17
    Nausea
         subjects affected / exposed
    25 / 228 (10.96%)
    25 / 232 (10.78%)
         occurrences all number
    29
    27
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    12 / 228 (5.26%)
    9 / 232 (3.88%)
         occurrences all number
    15
    12
    Dyspnoea
         subjects affected / exposed
    10 / 228 (4.39%)
    15 / 232 (6.47%)
         occurrences all number
    10
    17
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    18 / 228 (7.89%)
    15 / 232 (6.47%)
         occurrences all number
    19
    16
    Anxiety
         subjects affected / exposed
    12 / 228 (5.26%)
    4 / 232 (1.72%)
         occurrences all number
    13
    4
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    42 / 228 (18.42%)
    31 / 232 (13.36%)
         occurrences all number
    65
    40
    Back pain
         subjects affected / exposed
    22 / 228 (9.65%)
    18 / 232 (7.76%)
         occurrences all number
    25
    19
    Myalgia
         subjects affected / exposed
    16 / 228 (7.02%)
    8 / 232 (3.45%)
         occurrences all number
    19
    11
    Pain in extremity
         subjects affected / exposed
    17 / 228 (7.46%)
    11 / 232 (4.74%)
         occurrences all number
    22
    15

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Dec 2012
    Clarified that patients who continued to receive open-label study treatment beyond the closure of the database were no longer required to continue with the placebo treatment. Editorial corrections included. Eligibility criteria updated. The methods for unblinding the study were updated. Updates and clarifications were made to the concomitant and post-study treatment. Clarified that the statistical analysis was to be performed on the oestrogen containing hormone replacement therapy data.
    01 Dec 2017
    Clarified that the delay of final OS analysis would be to 75% maturity. Updated to describe the investigational product supply in the post OS analysis phase. Updated to explain that serious adverse events (SAEs) were to be recorded on a paper-based SAE report form in the post-OS analysis period.
    17 Dec 2021
    Change of final OS analysis trigger from when 75% of patients died to: when at least 65% of patients died and at least 8 years passed since the last patient was enrolled. Updated with details of provision of fulvestrant and anastrozole being supplied as a continued access phase after final database lock. Clarified that Coronavirus Disease-2019 (COVID-19) vaccination with authorised vaccines was permitted at the discretion of the investigator. Change in the wording of SAE reporting as opposed to SAE recorded. Updated the study timetable details. Change of contract research organization name from Quintiles to IQVIA. Other minor corrections/updates were made throughout the document.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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