Breast Cancer
Conditions
Brief summary
To compare the anti-tumour effects as measured by changes in various biomarkers, of a combination of Faslodex and Arimidex with Faslodex alone and Arimidex alone in postmenopausal women patients with primary breast cancer who are awaiting curative-intent surgery.
Interventions
DRUGFulvestrant
500 mg intramuscular injection
DRUGAnastrazole
oral tablet
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Postmenopausal women. * Biopsy confirmation of primary breast cancer. * Oestrogen receptor positive tumour. * Fit for surgery within one month. * Written informed consent to participate in the study
Exclusion criteria
* Previous treatment with any anti-hormonal therapy for breast cancer. * Previous radiotherapy to the primary tumour. * Previous chemotherapy for the primary tumour.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline to Time of Surgery in Oestrogen Receptor (ER) H-score: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the ER H-score. | Surgery (SRG) was to be performed between days 15 and 22 after baseline (BL) | For each sample, the ER H-score is calculated from the percentage of cells staining very weak (+/-); weak (+); moderate (++); or strong (+++) as follows: H-score = \[(0.5 x percent +/-) + (1 x percent +) + (2 x percent ++) + (3 x percent +++)\]. Range 0-300. The greater the change from baseline (randomization) in ER H-score, the greater the blockage of ER expression and the greater the potential anti-tumour activity. Percentage change from baseline=\[(SRG - BL)/BL\]x100 |
| Percentage Change From Baseline to Time of Surgery in Progesterone Receptor (PgR) H-score: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the PgR H-score. | Surgery (SRG) was to be performed between days 15 and 22 after baseline (BL) | For each sample, the PgR H-score is calculated from the percentage of cells staining very weak (+/-); weak (+); moderate (++); or strong (+++) as follows: H-score = \[(0.5 x percent+/-) + (1 x percent+) + (2 x percent++) + (3 x percent+++)\]. Range 0-300. The greater the change from baseline (randomization in PgR H-score, the greater the blockage of PgR expression and the greater the potential anti-tumour activity. Percentage change from baseline=\[(SRG - BL)/BL\]x100 |
| Percentage Change From Baseline to Time of Surgery in Ki67 Labelling Index: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the Ki67 Labelling Index. | Surgery (SRG) was to be performed between days 15 and 22 after baseline (BL) | For each sample, the Ki67 labelling index is calculated as the percentage of cells stained positive for Ki67. Range 0-100. The greater the change from baseline (randomization) in Ki67 labelling index, the greater the blockage of Ki67 expression and the greater the potential anti-tumour activity. Percentage change from baseline=\[(SRG - BL)/BL\]x100 |
Countries
United Kingdom
Participant flow
Recruitment details
Postmenopausal women with oestrogen receptor positive breast cancer, awaiting curative-intent surgery were recruited to 4 medical centres within the UK.
Pre-assignment details
121 patients had baseline biopsy and were randomised 1:1:1. 120 patients received 14 to 21 days therapy. Surgery was actually performed between day 13 and 28 and a tumour sample was taken. Safety data is presented for all 120 patients who received therapy. The demography data are summarized for the population who had a usable tumour sample.
Participants by arm
| Arm | Count |
|---|---|
| Fulvestrant Fulvestrant 500 mg once monthly injection | 35 |
| Fulvestrant + Anastrozole Fulvestrant 500 mg once monthly injection + Anastrozole 1 mg once daily tablet | 31 |
| Anastrozole Anastrozole 1 mg once daily tablet | 37 |
| Total | 103 |
Baseline characteristics
| Characteristic | Fulvestrant | Fulvestrant + Anastrozole | Anastrozole | Total |
|---|---|---|---|---|
| Age, Customized 50 - 59 years | 7 Participants 8.5 | 13 Participants 10.5 | 10 Participants 8.7 | 30 Participants 9 |
| Age, Customized 60 - 69 years | 13 Participants | 7 Participants | 14 Participants | 34 Participants |
| Age, Customized 70 - 79 years | 13 Participants | 6 Participants | 9 Participants | 28 Participants |
| Age, Customized 80 - 89 years | 2 Participants | 3 Participants | 2 Participants | 7 Participants |
| Age, Customized Not available | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 35 Participants | 31 Participants | 37 Participants | 103 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 40 | 13 / 40 | 17 / 40 |
| serious Total, serious adverse events | 0 / 40 | 3 / 40 | 2 / 40 |
Outcome results
Primary
Percentage Change From Baseline to Time of Surgery in Ki67 Labelling Index: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the Ki67 Labelling Index.
For each sample, the Ki67 labelling index is calculated as the percentage of cells stained positive for Ki67. Range 0-100. The greater the change from baseline (randomization) in Ki67 labelling index, the greater the blockage of Ki67 expression and the greater the potential anti-tumour activity. Percentage change from baseline=\[(SRG - BL)/BL\]x100
Time frame: Surgery (SRG) was to be performed between days 15 and 22 after baseline (BL)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Percentage Change From Baseline to Time of Surgery in Ki67 Labelling Index: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the Ki67 Labelling Index. | -62 Percentage change from baseline | Standard Error 4 |
| Fulvestrant + Anastrozole | Percentage Change From Baseline to Time of Surgery in Ki67 Labelling Index: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the Ki67 Labelling Index. | -68 Percentage change from baseline | Standard Error 6 |
| Anastrozole | Percentage Change From Baseline to Time of Surgery in Ki67 Labelling Index: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the Ki67 Labelling Index. | -75 Percentage change from baseline | Standard Error 4 |
Primary
Percentage Change From Baseline to Time of Surgery in Oestrogen Receptor (ER) H-score: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the ER H-score.
For each sample, the ER H-score is calculated from the percentage of cells staining very weak (+/-); weak (+); moderate (++); or strong (+++) as follows: H-score = \[(0.5 x percent +/-) + (1 x percent +) + (2 x percent ++) + (3 x percent +++)\]. Range 0-300. The greater the change from baseline (randomization) in ER H-score, the greater the blockage of ER expression and the greater the potential anti-tumour activity. Percentage change from baseline=\[(SRG - BL)/BL\]x100
Time frame: Surgery (SRG) was to be performed between days 15 and 22 after baseline (BL)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Percentage Change From Baseline to Time of Surgery in Oestrogen Receptor (ER) H-score: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the ER H-score. | -37 Percentage change from baseline | Standard Error 4 |
| Fulvestrant + Anastrozole | Percentage Change From Baseline to Time of Surgery in Oestrogen Receptor (ER) H-score: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the ER H-score. | -38 Percentage change from baseline | Standard Error 5 |
| Anastrozole | Percentage Change From Baseline to Time of Surgery in Oestrogen Receptor (ER) H-score: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the ER H-score. | -7 Percentage change from baseline | Standard Error 6 |
Primary
Percentage Change From Baseline to Time of Surgery in Progesterone Receptor (PgR) H-score: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the PgR H-score.
For each sample, the PgR H-score is calculated from the percentage of cells staining very weak (+/-); weak (+); moderate (++); or strong (+++) as follows: H-score = \[(0.5 x percent+/-) + (1 x percent+) + (2 x percent++) + (3 x percent+++)\]. Range 0-300. The greater the change from baseline (randomization in PgR H-score, the greater the blockage of PgR expression and the greater the potential anti-tumour activity. Percentage change from baseline=\[(SRG - BL)/BL\]x100
Time frame: Surgery (SRG) was to be performed between days 15 and 22 after baseline (BL)
Population: nine patients with PgR=0 at baseline were excluded from analysis of PgR because the question of medical interest was the effect of treatment on PgR positive patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Percentage Change From Baseline to Time of Surgery in Progesterone Receptor (PgR) H-score: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the PgR H-score. | -31 Percentage change from baseline | Standard Error 8 |
| Fulvestrant + Anastrozole | Percentage Change From Baseline to Time of Surgery in Progesterone Receptor (PgR) H-score: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the PgR H-score. | -38 Percentage change from baseline | Standard Error 12 |
| Anastrozole | Percentage Change From Baseline to Time of Surgery in Progesterone Receptor (PgR) H-score: Antitumour Effects of Fulvestrant, Anastrozole and a Combination of Both as Measured by the PgR H-score. | -38 Percentage change from baseline | Standard Error 7 |