A Global Study to Compare the Effects of Fulvestrant and Arimidex in a Subset of Patients With Breast Cancer.

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)

Population: The ITT analysis set included all randomised patients.

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)

Population: The ITT analysis set included all randomised patients.

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

Population: The ITT analysis set included all randomised patients. Date of death of 2 participants were unknown in the Anastrozole 1mg arm, hence they were censored for OS analysis.

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)

Population: The ITT analysis set included all randomised patients.

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)

Population: 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).

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)

Population: 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).

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)

Population: The ITT analysis set included all randomised patients.

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)

Population: 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).

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)

Population: 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).