Breast Cancer
Conditions
Keywords
Hormone, receptor, positive, breast, cancer, first, relapse
Brief summary
The purpose of this study is to determine the efficacy of anastrozole monotherapy versus maximal oestrogen blockade with combinated therapy of fulvestrant and anastrozole compared with in treatment of hormone receptor positive women with first relapse of breast cancer.
Interventions
DRUGFulvestrant
intramuscular injection 250 mg loading dose (LD) regimen
DRUGAnastrozole
1 mg oral tablet
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Signed informed consent, postmenopausal females, histological or cytological confirmed oestrogene and/or progesterone (PgR) receptor positive breast cancer, local recurrence or metastasis
Exclusion criteria
* Previous systemic endocrine therapy for advanced or recurrent disease; prior fulvestrant therapy * Premenopausal women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) | RECIST assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009 | RECIST (Response Evaluation Criteria in Solid Tumours) assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009. TTP, time in months to worsen 'progression' according to RECIST criteria. (RECIST is a set of published rules that define when cancer patients improve respond, stay the same stableor worsen progression during treatments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Clinical Benefit Rate (CBR) Responders | RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009 | No. of patients who were clinical benefit responders over the no. of randomised patients x100. A clinical benefit responder = a patient whose best response is CR, PR or SD\>=24 weeks (where a best response of SD = no new lesions and for existing lesions; neither suffient shrinkage to count as PR nor sufficient growth to count as progression) |
| Duration of Response (DoR) | RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009 | Median time from randomisation until objective progression or death (in the absence of objective progression), measured only in those patients who are objective responders |
| Percentage of Evaluable Participants With Objective Response Rate (ORR) | RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009 | No. of patients who were objective responders over the no. of patients evaluable for response x100. An objective responder = a patient whose best response is either CR (disappearance of all lesions) or PR (\>= 30% shrinkage in the sum of the longest diamemeters of the measurable lesions + no new lesions + no progression of non-measurable lesions) |
| Time to Treatment Failure (TTF) | From randomisation until data cut-off on 30th April 2009 | Time from randomisation until the date of discontinuation of randomised treatment for any reason |
| Overall Survival (OS) | All deaths occurring between randomisation and data cut-off on 30th April 2009 are included. | Overall survival is equivalent to time to death. Time from randomisation until the date of death |
| Duration of Clinical Benefit (DoCB) | RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009 | Median time from randomisation until objective progression or death (in the absence of objective progression), measured only in those patients who are clinical benefit responders |
Countries
Canada, Costa Rica, Finland, France, Germany, Guatemala, Iceland, Italy, Norway, Portugal, Sweden, Turkey (Türkiye)
Participant flow
Recruitment details
258 patients were randomised to Fulvestrant + Anastrozole and 256 patients were randomised to Anastrozole. In each treatment group, there were 2 patients who did not receive any trial therapy and so have been excluded from the safety summaries.
Participants by arm
| Arm | Count |
|---|---|
| Fulvestrant + Anastrozole Fulvestrant 250 mg Loading Dose Regimen + Anastrozole 1 mg | 258 |
| Anastrozole Anastrozole 1 mg | 256 |
| Total | 514 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 6 |
| Overall Study | disease progression | 97 | 105 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Prematurely Discontinued | 1 | 0 |
| Overall Study | Protocol Violation | 6 | 5 |
| Overall Study | still ongoing at data cut-off | 41 | 46 |
| Overall Study | Withdrawal by Subject | 7 | 7 |
| Overall Study | withdrawn due to osteoporosis | 1 | 0 |
Baseline characteristics
| Characteristic | Fulvestrant + Anastrozole | Anastrozole | Total |
|---|---|---|---|
| Age Continuous | 65.2 Years STANDARD_DEVIATION 9.6 | 63.4 Years STANDARD_DEVIATION 10.3 | 64.3 Years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 258 Participants | 256 Participants | 514 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 | — / — | — / — |
| other Total, other adverse events | 161 / 256 | 178 / 254 |
| serious Total, serious adverse events | 40 / 256 | 45 / 254 |
Outcome results
Primary
Time to Progression (TTP)
RECIST (Response Evaluation Criteria in Solid Tumours) assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009. TTP, time in months to worsen 'progression' according to RECIST criteria. (RECIST is a set of published rules that define when cancer patients improve respond, stay the same stableor worsen progression during treatments.
Time frame: RECIST assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant + Anastrozole | Time to Progression (TTP) | 10.8 months |
| Anastrozole | Time to Progression (TTP) | 10.2 months |
Secondary
Duration of Clinical Benefit (DoCB)
Median time from randomisation until objective progression or death (in the absence of objective progression), measured only in those patients who are clinical benefit responders
Time frame: RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant + Anastrozole | Duration of Clinical Benefit (DoCB) | 18.5 months |
| Anastrozole | Duration of Clinical Benefit (DoCB) | 18.1 months |
Secondary
Duration of Response (DoR)
Median time from randomisation until objective progression or death (in the absence of objective progression), measured only in those patients who are objective responders
Time frame: RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant + Anastrozole | Duration of Response (DoR) | 22.3 months |
| Anastrozole | Duration of Response (DoR) | 18.2 months |
Secondary
Overall Survival (OS)
Overall survival is equivalent to time to death. Time from randomisation until the date of death
Time frame: All deaths occurring between randomisation and data cut-off on 30th April 2009 are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant + Anastrozole | Overall Survival (OS) | 37.8 months |
| Anastrozole | Overall Survival (OS) | 38.2 months |
Secondary
Percentage of Clinical Benefit Rate (CBR) Responders
No. of patients who were clinical benefit responders over the no. of randomised patients x100. A clinical benefit responder = a patient whose best response is CR, PR or SD\>=24 weeks (where a best response of SD = no new lesions and for existing lesions; neither suffient shrinkage to count as PR nor sufficient growth to count as progression)
Time frame: RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fulvestrant + Anastrozole | Percentage of Clinical Benefit Rate (CBR) Responders | 55.0 Percentage of participants |
| Anastrozole | Percentage of Clinical Benefit Rate (CBR) Responders | 55.1 Percentage of participants |
Secondary
Percentage of Evaluable Participants With Objective Response Rate (ORR)
No. of patients who were objective responders over the no. of patients evaluable for response x100. An objective responder = a patient whose best response is either CR (disappearance of all lesions) or PR (\>= 30% shrinkage in the sum of the longest diamemeters of the measurable lesions + no new lesions + no progression of non-measurable lesions)
Time frame: RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fulvestrant + Anastrozole | Percentage of Evaluable Participants With Objective Response Rate (ORR) | 31.8 Percentage of evaluable participants |
| Anastrozole | Percentage of Evaluable Participants With Objective Response Rate (ORR) | 33.6 Percentage of evaluable participants |
Secondary
Time to Treatment Failure (TTF)
Time from randomisation until the date of discontinuation of randomised treatment for any reason
Time frame: From randomisation until data cut-off on 30th April 2009
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant + Anastrozole | Time to Treatment Failure (TTF) | 12.4 months |
| Anastrozole | Time to Treatment Failure (TTF) | 11.4 months |