Metastatic Breast Cancer
Conditions
Keywords
oncology, cancer, breast cancer
Brief summary
The purpose of this study is to compare the efficacy and tolerability of Faslodex (fulvestrant) with Arimidex (anastrozole) in postmenopausal women with hormone receptor positive advanced breast cancer.
Interventions
DRUGfulvestrant
500 mg intramuscular injection
DRUGanastrozole
1 mg oral tablet
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed hormone receptor positive advanced breast cancer, postmenopausal women
Exclusion criteria
* Previous treatment for advanced breast cancer (previous treatment for early breast cancer is allowed).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate | From randomisation to data cut off (DCO) for primary analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for primary analysis was on 10th Jan 2008, 6 months after the last patient was enrolled. | A Clinical Benefit (CB) responder is defined as a patient having a best overall response of either complete response (CR), partial response (PR) or stable disease (SD) for at least 24 weeks evaluated according to modified RECIST. The Clinical Benefit Rate is the percentage of patients with CB. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | From randomisation to data cut off (DCO) for primary analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for primary analysis was on 10th Jan 2008, 6 months after the last patient was enrolled. | For each patient with measurable disease at baseline, the determination of the overall response for each visit was carried out using a SAS program per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete Response (CR): Disappearance of all target lesion (TL) and non-target lesions (NTLs) and no new lesions. Partial Response (PR): At least a 30% decrease in the sum of longest diameter of TLs (compared to baseline), no progression of NTLs and no new lesions. Objective response rate is defined as percentage of patients with either CR or PR. |
| Time to Progression | From randomisation to data cut off (DCO) for primary analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for primary analysis was on 10th Jan 2008, 6 months after the last patient was enrolled. | Time from randomization until earlier of disease progression or death. Progression was defined according to RECIST: a patient is determined to have progressed if they have progression of target lesions, clear progression of existing non-target lesions, or the appearance of one or more new lesions. Progression of target lesions is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum of LD recorded. Kaplan-Meier estimates of median for each treatment are reported. |
| Time to Treatment Failure | From randomisation to data cut off (DCO) for 75% treatment failure. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007. The DCO for 75% treatment failure was on 26 Mar 2010, 32 months after the last patient was enrolled. | Time from randomization to treatment discontinuation |
| Time to Progression (Investigator Assessed) | From randomisation to data cut off (DCO) for 75% treatment failure. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007. The DCO for 75% treatment failure was on 26 Mar 2010, 32 months after the last patient was enrolled. | Time from randomization to disease progression (investigator assessed) or death from any cause. Progression was defined by investigator opinion, as patients did not have formal RECIST visits in the follow-up period after the data cut off for the primary analysis of the study. |
Countries
Brazil, Bulgaria, Czechia, France, Italy, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
Postmenopausal women presenting with advanced breast cancer who had either never received endocrine therapy for advanced disease or had not received endocrine therapy in the previous 12 months in the adjuvant setting were recruited between 6th Feb 2006 and 11th July 2007.
Pre-assignment details
28 of the 233 enrolled patients were not randomized to treatment groups for the following reasons - 20 patients were incorrectly enrolled (ie did not comply with inclusion / exclusion criteria), 1 died, 1 had an adverse event, 4 voluntarily discontinued, 2 patients were not randomized for other non-specified reasons.
Participants by arm
| Arm | Count |
|---|---|
| Fulvestrant 500 mg Fulvestrant 500 mg | 102 |
| Anastrozole 1 mg Anastrozole 1 mg | 103 |
| Total | 205 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 63 | 74 |
| Overall Study | Did not consent to OS follow-up | 16 | 19 |
Baseline characteristics
| Characteristic | Fulvestrant 500 mg | Anastrozole 1 mg | Total |
|---|---|---|---|
| Age, Continuous | 66.6 Years STANDARD_DEVIATION 9 | 67.6 Years STANDARD_DEVIATION 9.3 | 67.1 Years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 102 Participants | 103 Participants | 205 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 63 / 102 | 74 / 103 |
| other Total, other adverse events | 71 / 101 | 70 / 103 |
| serious Total, serious adverse events | 24 / 101 | 22 / 103 |
Outcome results
Primary
Clinical Benefit Rate
A Clinical Benefit (CB) responder is defined as a patient having a best overall response of either complete response (CR), partial response (PR) or stable disease (SD) for at least 24 weeks evaluated according to modified RECIST. The Clinical Benefit Rate is the percentage of patients with CB.
Time frame: From randomisation to data cut off (DCO) for primary analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for primary analysis was on 10th Jan 2008, 6 months after the last patient was enrolled.
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fulvestrant 500 mg | Clinical Benefit Rate | 72.5 Percentage of Participants |
| Anastrozole 1 mg | Clinical Benefit Rate | 67.0 Percentage of Participants |
p-value: 0.38695% CI: [0.717, 2.38]Regression, Logistic
Secondary
Objective Response Rate
For each patient with measurable disease at baseline, the determination of the overall response for each visit was carried out using a SAS program per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete Response (CR): Disappearance of all target lesion (TL) and non-target lesions (NTLs) and no new lesions. Partial Response (PR): At least a 30% decrease in the sum of longest diameter of TLs (compared to baseline), no progression of NTLs and no new lesions. Objective response rate is defined as percentage of patients with either CR or PR.
Time frame: From randomisation to data cut off (DCO) for primary analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for primary analysis was on 10th Jan 2008, 6 months after the last patient was enrolled.
Population: Evaluable For Response Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fulvestrant 500 mg | Objective Response Rate | 36.0 Percentage of Participants |
| Anastrozole 1 mg | Objective Response Rate | 35.5 Percentage of Participants |
p-value: 0.94795% CI: [0.556, 1.874]Regression, Logistic
Secondary
Time to Progression
Time from randomization until earlier of disease progression or death. Progression was defined according to RECIST: a patient is determined to have progressed if they have progression of target lesions, clear progression of existing non-target lesions, or the appearance of one or more new lesions. Progression of target lesions is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum of LD recorded. Kaplan-Meier estimates of median for each treatment are reported.
Time frame: From randomisation to data cut off (DCO) for primary analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for primary analysis was on 10th Jan 2008, 6 months after the last patient was enrolled.
Population: Full Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant 500 mg | Time to Progression | NA Day |
| Anastrozole 1 mg | Time to Progression | 381 Day |
p-value: 0.049695% CI: [0.3929, 0.9991]Log Rank
Secondary
Time to Progression (Investigator Assessed)
Time from randomization to disease progression (investigator assessed) or death from any cause. Progression was defined by investigator opinion, as patients did not have formal RECIST visits in the follow-up period after the data cut off for the primary analysis of the study.
Time frame: From randomisation to data cut off (DCO) for 75% treatment failure. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007. The DCO for 75% treatment failure was on 26 Mar 2010, 32 months after the last patient was enrolled.
Population: Full Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant 500 mg | Time to Progression (Investigator Assessed) | 712 Day |
| Anastrozole 1 mg | Time to Progression (Investigator Assessed) | 400 Day |
p-value: 0.0195% CI: [0.47, 0.92]Log Rank
p-value: 0.0195% CI: [0.46, 0.9]Regression, Cox
Secondary
Time to Treatment Failure
Time from randomization to treatment discontinuation
Time frame: From randomisation to data cut off (DCO) for 75% treatment failure. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007. The DCO for 75% treatment failure was on 26 Mar 2010, 32 months after the last patient was enrolled.
Population: Full analysis set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant 500 mg | Time to Treatment Failure | 536 Day |
| Anastrozole 1 mg | Time to Treatment Failure | 387 Day |
p-value: 0.0595% CI: [0.54, 1]Log Rank
p-value: 0.0495% CI: [0.52, 0.98]Regression, Cox
Post Hoc
Overall Survival
Time from randomization to death (any cause)
Time frame: From randomization to data cut off (DCO) for 65% OS analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for 65% OS analysis was on 15 Jul 2014, 7 years after the last patient was enrolled.
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant 500 mg | Overall Survival | 54.1 Month |
| Anastrozole 1 mg | Overall Survival | 48.4 Month |
p-value: 0.04195% CI: [0.5, 0.98]Log Rank
p-value: 0.12695% CI: [0.54, 1.08]Regression, Cox