Breast Cancer
Conditions
Keywords
Hormone receptor positive breast cancer
Brief summary
The study assesses the effect of further 2 years vs further 5 years of adjuvant treatment with anastrozole after initial 5 years of adjuvant endocrine therapy.
Detailed description
ABCSG 16 S.A.L.S.A is assessing the effect of further 2 years vs further 5 years of adjuvant treatment with anastrozole after initial 5 years of adjuvant endocrine therapy. S.A.L.S.A. is a randomized open multicentered phase III study comparing the efficacy of secondary adjuvant endokrine treatment of Arimidex® (Anastrozol) for 2 or 5 years after primary adjuvant endokrine therapy in patients with hormonreceptor positive mammakarzinom. Patients are examined at screening, after 6 months, then every year until 5 years. The subsequent yearly follow up with mammographie and clinical examination ends 10 years after the screening. S.A.L.S.A. started in February 2004 and has recruited 3484 patients until June 2010 at 78 sites all over Austria. Primary Endpoint: 1\. Proof of the effect of 2 years versus 5 years of Anastrozol after 5 years of adjuvant endocrine therapy on the disease free survival Secondary endpoint: 1. Proof of the effect of 2 years versus 5 years of Anastrozol after 5 years of adjuvant endocrine therapy on the overall survival 2. Comparison of fracture rate in both therapy groups 3. Comparison of incidence of 1. a secondary carcinoma except the contralateral mammacarcinoma 2. contralateral mammacarcinoma in both therapie groups
Interventions
DRUGAnastrozole
1mg tablet daily
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Postmenopausal patients with histologically confirmed, local radically treated invasive or minimal-invasiv Mammacarcinom with or without previous chemotherapie and/or radiotherapie. 2. No distant metastasis at randomization 3. No relapse at randomization 4. TNM- classification at time of diagnosis: T1-3, N0 and N+, M0 5. Estrogen- and or progesterone positive before the beginningof primary endocrine therapy 6. Endocrine therapy for 5 years (maximum deviation ±12 months) 7. Therapy break (from the preliminary therapie) maximum 12 months. 8. Informed Consent before the randomisation
Exclusion criteria
1. Premenopausal patients or patients with non definable menopausal statusat time of randomisation 2. Apparent secondary malignant tumor or status after secondary malignant tumor (Exceptions: simultaniously appearing bilateral breast carcinoma, estrogen- and or progesteronereceptor positive on both sides at the time of diagnosis; in situ carcinomaof the cervix and basal cell carcinoma of the skin) 3. General contraindication respectively hypersensitivity to Anastrozol. 4. In-situ carcinoma of any size with or without Mb. Paget of the Mamilla respectively T4 tumor at the time of first diagnosis. 5. Receptor unknown or negative at time of diagnosis respectively at beginning of primary endocrine therapy 6. Known liver- and/or kidneyinsufficiency 7. Performance Index \>2 according to WHO 8. Regular intake of hormon supplement as well as Hormone Replacement Therapy (HRT) more than 6 months since primary surgery of the mamma carcinoma 9. Serious accessory disease, that prevents the adjuvant therapy according to protocol and/or the regular follow-up care. 10. Lacking compliance of the patient 11. Legal incompetence and/or other circumstances, that prevent the patient from understanding the nature, meaning and consequences of the clinical trial 12. Existing psychiatrical diseaseaccording to ICD (especially alcohol addiction) et the time of admission into the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival After Prolonged Endocrine Treatment | DFS was defined as the time from two years after randomization to the earliest occurrence of loco-regional recurrence, distant recurrence, contralateral new breast cancer, second cancer or death from any cause, assessed up to a maximum of 8.5 years | To determine whether 5 years of additional Anastrozole was more effective than 2 years of additional Anastrozole after 5 years of adjuvant endocrine therapy in terms of disease-free survival. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival After Prolonged Endocrine Treatment | Overall survival was defined as the time from two years after randomization to death due to any cause, assessed up to a maximum of 8.5 years | To determine whether 5 years of additional Anastrozole was more effective than 2 years of additional Anastrozole after 5 years of adjuvant endocrine therapy in terms of overall survival. |
| Time to First Clinical Fracture | Time to first clinical fracture was defined as time to first clinical fracture, in the period from 2 years until 5 years after randomization for each patient. | To determine the effect of 2 years versus 5 years of additional Anastrozole after 5 years of adjuvant endocrine therapy on the time to first clinical fracture. Patients without clinical fractures where censored at their last therapy visit (approximately 5 years after randomization). |
| Time to Secondary Carcinoma | Risk of secondary carcinoma was defined as the time from two years after randomization to first occurrence of new secondary cancer without new breast cancer (local or contralateral), assessed up to a maximum of 8.5 years | To determine whether 5 years of additional Anastrozole was more effective than 2 years of additional Anastrozole after 5 years of adjuvant endocrine therapy in terms of lowering the risk of secondary carcinoma. Subjects without secondary cancer event were censored at the last date when they were known to be secondary cancer free. |
| Time to Contralateral Breast Cancer | Risk of contralateral breast cancer was defined as the time from two years after randomization to first occurrence of new contralateral breast cancer, assessed up to a maximum of 8.5 years | To determine whether 5 years of additional Anastrozole was more effective than 2 years of additional Anastrozole after 5 years of adjuvant endocrine therapy in terms of lowering the risk of contralateral breast cancer. Subjects without contralateral breast cancer event were censored at the last date when they were known to be contralateral breast cancer free. |
Countries
Austria
Participant flow
Recruitment details
The first patient was randomized Feb 26, 2004, the last patient was randomized June 30, 2010. Randomization took place in 75 Austrian clinical sites. In total, 3,484 patients were enrolled.
Pre-assignment details
Fourteen patients did not sign the Informed Consent, resulting in 3,470 patients who started the trial.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Anastrozol 1 mg per day for 2 years | 1,732 |
| Arm B: Anastrozol 1 mg per day for 5 years | 1,738 |
| Total | 3,470 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 206 | 207 |
| Overall Study | Discontinuation by sponsor | 580 | 593 |
| Overall Study | Lost to Follow-up | 9 | 5 |
| Overall Study | Other reasons | 10 | 9 |
| Overall Study | Protocol Violation | 30 | 32 |
| Overall Study | Withdrawal by Subject | 37 | 50 |
Baseline characteristics
| Characteristic | Arm A: Anastrozol | Arm B: Anastrozol | Total |
|---|---|---|---|
| Age, Continuous | 65 years | 64 years | 64 years |
| Axillary Surgery No | 386 Participants | 405 Participants | 791 Participants |
| Axillary Surgery Unknown | 1 Participants | 2 Participants | 3 Participants |
| Axillary Surgery Yes | 1345 Participants | 1331 Participants | 2676 Participants |
| Estrogen Receptor Status Negative | 45 Participants | 46 Participants | 91 Participants |
| Estrogen Receptor Status Positive (+/++/+++) | 1686 Participants | 1689 Participants | 3375 Participants |
| Estrogen Receptor Status Unknown | 1 Participants | 3 Participants | 4 Participants |
| pN-stage pN0 | 1140 Participants | 1162 Participants | 2302 Participants |
| pN-stage pN1 | 551 Participants | 523 Participants | 1074 Participants |
| pN-stage pN2 | 30 Participants | 41 Participants | 71 Participants |
| pN-stage pN3 | 7 Participants | 8 Participants | 15 Participants |
| pN-stage Unknown | 4 Participants | 4 Participants | 8 Participants |
| Previous Chemotherapy Chemotherapy containing anthracycline | 246 Participants | 236 Participants | 482 Participants |
| Previous Chemotherapy Chemotherapy containing taxane | 93 Participants | 95 Participants | 188 Participants |
| Previous Chemotherapy No chemotherapy | 1224 Participants | 1241 Participants | 2465 Participants |
| Previous Chemotherapy Other chemotherapy | 167 Participants | 163 Participants | 330 Participants |
| Previous Chemotherapy Unknown | 2 Participants | 3 Participants | 5 Participants |
| Previous Endocrine Therapy 2 years of anti-estrogen + 3 years Anastrozole | 416 Participants | 419 Participants | 835 Participants |
| Previous Endocrine Therapy 5 years of anti-estrogen | 855 Participants | 862 Participants | 1717 Participants |
| Previous Endocrine Therapy Another, comparable endocrine therapy | 459 Participants | 454 Participants | 913 Participants |
| Previous Endocrine Therapy Unknown | 2 Participants | 3 Participants | 5 Participants |
| Previous Radiotherapy No | 356 Participants | 327 Participants | 683 Participants |
| Previous Radiotherapy Unknown | 3 Participants | 4 Participants | 7 Participants |
| Previous Radiotherapy Yes | 1373 Participants | 1407 Participants | 2780 Participants |
| Progesterone Receptor Status Negative | 332 Participants | 356 Participants | 688 Participants |
| Progesterone Receptor Status Positive (+/++/+++) | 1398 Participants | 1375 Participants | 2773 Participants |
| Progesterone Receptor Status Unknown | 2 Participants | 7 Participants | 9 Participants |
| pT-stage pT1 | 1254 Participants | 1254 Participants | 2508 Participants |
| pT-stage pT2 | 440 Participants | 442 Participants | 882 Participants |
| pT-stage pT3 | 30 Participants | 32 Participants | 62 Participants |
| pT-stage pTx | 4 Participants | 6 Participants | 10 Participants |
| pT-stage Unknown | 4 Participants | 4 Participants | 8 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sentinel Node Biopsy No | 900 Participants | 887 Participants | 1787 Participants |
| Sentinel Node Biopsy Unknown | 12 Participants | 15 Participants | 27 Participants |
| Sentinel Node Biopsy Yes | 820 Participants | 836 Participants | 1656 Participants |
| Sex: Female, Male Female | 1732 Participants | 1738 Participants | 3470 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Surgery Type Breast-conserving surgery | 1360 Participants | 1405 Participants | 2765 Participants |
| Surgery Type Modified radical mastectomy | 367 Participants | 319 Participants | 686 Participants |
| Surgery Type Other | 4 Participants | 12 Participants | 16 Participants |
| Surgery Type Unknown | 1 Participants | 2 Participants | 3 Participants |
| Tumor Grading G1 | 247 Participants | 261 Participants | 508 Participants |
| Tumor Grading G2 | 1107 Participants | 1090 Participants | 2197 Participants |
| Tumor Grading G3 | 326 Participants | 348 Participants | 674 Participants |
| Tumor Grading GX | 27 Participants | 12 Participants | 39 Participants |
| Tumor Grading Unknown | 25 Participants | 27 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 207 / 1,738 | 207 / 1,732 |
| other Total, other adverse events | 0 / 1,710 | 0 / 1,705 |
| serious Total, serious adverse events | 687 / 1,710 | 452 / 1,705 |
Outcome results
Primary
Disease-free Survival After Prolonged Endocrine Treatment
To determine whether 5 years of additional Anastrozole was more effective than 2 years of additional Anastrozole after 5 years of adjuvant endocrine therapy in terms of disease-free survival.
Time frame: DFS was defined as the time from two years after randomization to the earliest occurrence of loco-regional recurrence, distant recurrence, contralateral new breast cancer, second cancer or death from any cause, assessed up to a maximum of 8.5 years
Population: Per-Protocol (PP) Population, defined as all randomized patients who signed the informed consent who complied with the inclusion and exclusion criteria, who had at least one follow-up examination after randomization and who survived without recurrence for two years.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Anastrozol | Disease-free Survival After Prolonged Endocrine Treatment | NA Years |
| Arm B: Anastrozol | Disease-free Survival After Prolonged Endocrine Treatment | NA Years |
Comparison: Arm A: Anastrozole for 2 yerars Arm B: Anastrozole for 5 years Null hypothesis: there is no difference between the two treatment arms in the probability of a DFS eventp-value: 0.42595% CI: [0.79, 1.11]Log Rank
Secondary
Overall Survival After Prolonged Endocrine Treatment
To determine whether 5 years of additional Anastrozole was more effective than 2 years of additional Anastrozole after 5 years of adjuvant endocrine therapy in terms of overall survival.
Time frame: Overall survival was defined as the time from two years after randomization to death due to any cause, assessed up to a maximum of 8.5 years
Population: All randomized patients who signed the informed consent and who did not die during two first two years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Anastrozol | Overall Survival After Prolonged Endocrine Treatment | NA Years |
| Arm B: Anastrozol | Overall Survival After Prolonged Endocrine Treatment | NA Years |
Comparison: Arm A: Anastrozole for 2 yerars Arm B: Anastrozole for 5 years Null hypothesis: there is no difference between the two treatment arms in the probability of a death eventp-value: 0.86795% CI: [0.83, 1.25]Log Rank
Secondary
Time to Contralateral Breast Cancer
To determine whether 5 years of additional Anastrozole was more effective than 2 years of additional Anastrozole after 5 years of adjuvant endocrine therapy in terms of lowering the risk of contralateral breast cancer. Subjects without contralateral breast cancer event were censored at the last date when they were known to be contralateral breast cancer free.
Time frame: Risk of contralateral breast cancer was defined as the time from two years after randomization to first occurrence of new contralateral breast cancer, assessed up to a maximum of 8.5 years
Population: All randomized patients who signed the informed consent and had no contralateral mammacarcinoma during the first two years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Anastrozol | Time to Contralateral Breast Cancer | NA Years |
| Arm B: Anastrozol | Time to Contralateral Breast Cancer | NA Years |
Comparison: Arm A: Anastrozole for 2 years Arm B: Anastrozole for 5 years Null hypothesis: there is no difference between the two treatment arms in the probability of the occurrence of contralateral mammacarcinomap-value: 0.53195% CI: [0.75, 1.77]Log Rank
Secondary
Time to First Clinical Fracture
To determine the effect of 2 years versus 5 years of additional Anastrozole after 5 years of adjuvant endocrine therapy on the time to first clinical fracture. Patients without clinical fractures where censored at their last therapy visit (approximately 5 years after randomization).
Time frame: Time to first clinical fracture was defined as time to first clinical fracture, in the period from 2 years until 5 years after randomization for each patient.
Population: All randomized patients who signed the informed consent and who had no fractures during the first two years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Anastrozol | Time to First Clinical Fracture | NA Years |
| Arm B: Anastrozol | Time to First Clinical Fracture | NA Years |
Comparison: Arm A: Anastrozole for 2 yerars Arm B: Anastrozole for 5 years Null hypothesis: there is no difference between the two treatment arms in the probability of a fracturep-value: 0.05295% CI: [1, 1.84]Log Rank
Secondary
Time to Secondary Carcinoma
To determine whether 5 years of additional Anastrozole was more effective than 2 years of additional Anastrozole after 5 years of adjuvant endocrine therapy in terms of lowering the risk of secondary carcinoma. Subjects without secondary cancer event were censored at the last date when they were known to be secondary cancer free.
Time frame: Risk of secondary carcinoma was defined as the time from two years after randomization to first occurrence of new secondary cancer without new breast cancer (local or contralateral), assessed up to a maximum of 8.5 years
Population: All randomized patients who signed the informed consent and had no secondary carcinoma (excluding contralateral mammacarcinoma) during the first two years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Anastrozol | Time to Secondary Carcinoma | NA Years |
| Arm B: Anastrozol | Time to Secondary Carcinoma | NA Years |
Comparison: Arm A: Anastrozole for 2 yerars Arm B: Anastrozole for 5 years Null hypothesis: there is no difference between the two treatment arms in the probability of the occurrence of secondary carcinomap-value: 0.67895% CI: [0.81, 1.38]Log Rank