Breast Cancer
Conditions
Keywords
Breast cancer, letrozole, anastrozole, adjuvant, postmenopausal, FACE
Brief summary
Eligible patients will be post-menopausal hormone receptor- and lymph node-positive females who recently underwent primary surgery for breast cancer. Patients will be randomized to letrozole (2.5 mg per day for 5 years) vs anastrozole (1 mg per day for 5 years). Follow up will occur for 5 years after the completion of enrollment for survival and disease status updates.
Interventions
DRUGLetrozole
2.5 mg tablets
DRUGAnastrozole
1 mg tablets
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
33 Years to 96 Years
Healthy volunteers
No
Inclusion criteria
* Recent primary surgery for breast cancer * Early stage breast cancer * Postmenopausal * Hormone receptor positive * Positive lymph node involvement
Exclusion criteria
* Metastatic disease * Presence of contralateral breast cancer including DCIS * Progression Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival | 84 months | Disease-free survival was defined as the time from the date of randomization to the date of the first documentation of re-occurrence of invasive breast cancer in local, regional or distant sites, new invasive breast cancer in the contra-lateral breast, or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Development of Distant Metastases | 84 months | Time to development of distant metastases was defined as the time from date of randomization to the date of the first development of any recurrent or metastatic disease in sites other than the local mastectomy scar, the ipsilateral breast in case of breast conservation or the contra lateral breast. |
| Time to Development of Contra Lateral Breast Cancer | 84 months | Time to development of contra lateral breast cancer was defined as the time from the date of randomization to the date of the first development of any disease in the contra lateral breast. |
| Distant Disease-free Survival | 84 months | Distant disease-free survival was defined as the time from date of randomization to the date of the first development of any relapse at a distant site or death from any cause. |
| Overall Survival | 84 months | Overall survival was defined as the time from the date of randomization to the date of death from any cause. |
| Percentage of Participants Who Experienced Clinical Fracture Events | 84 months | The incidence of clinical fractures was analyzed. |
| Percentage of Participants Who Experienced Cardiovascular Events | 84 months | The incidence of ischemic heart disease, cardiac failures, cerebrovascular accidents and thromboembolic events was analyzed. |
| Change From Baseline in Serum Lipid Profiles | baseline, 6, 12, 24, 36, 48 and 60 months | Total cholesterol was analyzed to assess the impact on serum lipids profiles. The adjusted means was calculated. |
Countries
Australia, Austria, Belgium, Canada, China, Denmark, France, Germany, Ireland, Israel, Italy, Japan, Netherlands, Norway, South Korea, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Participants, who had recently undergone surgery, were randomly assigned in 1:1 ratio to letrozole or anastrozole. Participants received daily treatment until disease recurrence/relapse or for a maximum of 5 years. Participants underwent post-treatment long term follow-up for disease-free survival and overall survival.
Participants by arm
| Arm | Count |
|---|---|
| Letrozole 2.5 mg by mouth (p.o.) once daily | 2,061 |
| Anastrozole 1 mg p.o. once daily | 2,075 |
| Total | 4,136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory values | 4 | 0 |
| Overall Study | Abnormal test procedure(s) result | 49 | 61 |
| Overall Study | Administrative problems | 22 | 25 |
| Overall Study | Adverse Event | 311 | 296 |
| Overall Study | Death | 28 | 47 |
| Overall Study | Disease progression | 196 | 216 |
| Overall Study | Lost to Follow-up | 28 | 35 |
| Overall Study | Protocol deviation | 17 | 19 |
| Overall Study | Protocol Violation | 35 | 30 |
| Overall Study | Withdrawal by Subject | 71 | 79 |
Baseline characteristics
| Characteristic | Letrozole | Anastrozole | Total |
|---|---|---|---|
| Age, Continuous | 63.2 Years STANDARD_DEVIATION 8.48 | 63.1 Years STANDARD_DEVIATION 8.45 | 63.2 Years STANDARD_DEVIATION 8.46 |
| Sex/Gender, Customized Female | 2061 Participants | 2075 Participants | 4136 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1,747 / 2,049 | 1,762 / 2,062 |
| serious Total, serious adverse events | 486 / 2,049 | 520 / 2,062 |
Outcome results
Primary
Disease Free Survival
Disease-free survival was defined as the time from the date of randomization to the date of the first documentation of re-occurrence of invasive breast cancer in local, regional or distant sites, new invasive breast cancer in the contra-lateral breast, or death from any cause.
Time frame: 84 months
Population: Intent-to-treat (ITT) - the ITT contained randomized participants who had no protocol deviations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Letrozole | Disease Free Survival | NA Months |
| Anastrozole | Disease Free Survival | NA Months |
p-value: 0.315Log Rank
Secondary
Change From Baseline in Serum Lipid Profiles
Total cholesterol was analyzed to assess the impact on serum lipids profiles. The adjusted means was calculated.
Time frame: baseline, 6, 12, 24, 36, 48 and 60 months
Population: Safety Set: The safety set included randomized participants who received at least one of study medication and had at least one post baseline assessment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Letrozole | Change From Baseline in Serum Lipid Profiles | 6 months | 5.643 mg/dL |
| Letrozole | Change From Baseline in Serum Lipid Profiles | 12 months | 5.569 mg/dL |
| Letrozole | Change From Baseline in Serum Lipid Profiles | 24 months | 5.508 mg/dL |
| Letrozole | Change From Baseline in Serum Lipid Profiles | 36 months | 5.429 mg/dL |
| Letrozole | Change From Baseline in Serum Lipid Profiles | 48 months | 5.395 mg/dL |
| Letrozole | Change From Baseline in Serum Lipid Profiles | 60 months | 5.375 mg/dL |
| Anastrozole | Change From Baseline in Serum Lipid Profiles | 48 months | 5.366 mg/dL |
| Anastrozole | Change From Baseline in Serum Lipid Profiles | 6 months | 5.553 mg/dL |
| Anastrozole | Change From Baseline in Serum Lipid Profiles | 36 months | 5.427 mg/dL |
| Anastrozole | Change From Baseline in Serum Lipid Profiles | 12 months | 5.511 mg/dL |
| Anastrozole | Change From Baseline in Serum Lipid Profiles | 60 months | 5.368 mg/dL |
| Anastrozole | Change From Baseline in Serum Lipid Profiles | 24 months | 5.436 mg/dL |
Secondary
Distant Disease-free Survival
Distant disease-free survival was defined as the time from date of randomization to the date of the first development of any relapse at a distant site or death from any cause.
Time frame: 84 months
Population: Intent-to-treat (ITT) - the ITT contained randomized participants who had no protocol deviations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Letrozole | Distant Disease-free Survival | NA Months |
| Anastrozole | Distant Disease-free Survival | NA Months |
Secondary
Overall Survival
Overall survival was defined as the time from the date of randomization to the date of death from any cause.
Time frame: 84 months
Population: Intent-to-treat (ITT) - the ITT contained randomized participants who had no protocol deviations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Letrozole | Overall Survival | NA Months |
| Anastrozole | Overall Survival | NA Months |
Secondary
Percentage of Participants Who Experienced Cardiovascular Events
The incidence of ischemic heart disease, cardiac failures, cerebrovascular accidents and thromboembolic events was analyzed.
Time frame: 84 months
Population: Safety Set: The safety set included randomized participants who received at least one of study medication and had at least one post baseline assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Letrozole | Percentage of Participants Who Experienced Cardiovascular Events | Ischemic heart disease | 2.4 Percentage of participants |
| Letrozole | Percentage of Participants Who Experienced Cardiovascular Events | Cardiac failures | 1.5 Percentage of participants |
| Letrozole | Percentage of Participants Who Experienced Cardiovascular Events | Cerebrovascular accidents | 1.6 Percentage of participants |
| Letrozole | Percentage of Participants Who Experienced Cardiovascular Events | Thromboembolic events | 1.2 Percentage of participants |
| Anastrozole | Percentage of Participants Who Experienced Cardiovascular Events | Thromboembolic events | 1.2 Percentage of participants |
| Anastrozole | Percentage of Participants Who Experienced Cardiovascular Events | Ischemic heart disease | 1.5 Percentage of participants |
| Anastrozole | Percentage of Participants Who Experienced Cardiovascular Events | Cerebrovascular accidents | 1.5 Percentage of participants |
| Anastrozole | Percentage of Participants Who Experienced Cardiovascular Events | Cardiac failures | 0.7 Percentage of participants |
Secondary
Percentage of Participants Who Experienced Clinical Fracture Events
The incidence of clinical fractures was analyzed.
Time frame: 84 months
Population: Safety Set: The safety set included randomized participants who received at least one of study medication and had at least one post baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Letrozole | Percentage of Participants Who Experienced Clinical Fracture Events | 9.3 Percentage of participants |
| Anastrozole | Percentage of Participants Who Experienced Clinical Fracture Events | 8.1 Percentage of participants |
Secondary
Time to Development of Contra Lateral Breast Cancer
Time to development of contra lateral breast cancer was defined as the time from the date of randomization to the date of the first development of any disease in the contra lateral breast.
Time frame: 84 months
Population: Intent-to-treat (ITT) - the ITT contained randomized participants who had no protocol deviations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Letrozole | Time to Development of Contra Lateral Breast Cancer | NA Months |
| Anastrozole | Time to Development of Contra Lateral Breast Cancer | NA Months |
Secondary
Time to Development of Distant Metastases
Time to development of distant metastases was defined as the time from date of randomization to the date of the first development of any recurrent or metastatic disease in sites other than the local mastectomy scar, the ipsilateral breast in case of breast conservation or the contra lateral breast.
Time frame: 84 months
Population: Intent-to-treat (ITT) - the ITT contained randomized participants who had no protocol deviations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Letrozole | Time to Development of Distant Metastases | NA Months |
| Anastrozole | Time to Development of Distant Metastases | NA Months |