Breast Neoplasms
Conditions
Brief summary
To compare the effects of exemestane for 5 years versus tamoxifen and exemestane given sequentially over 5 years in the adjuvant treatment of postmenopausal women with early breast cancer. This Pfizer sponsored trial is part of an international collaboration of investigators conducting 7 similar yet independent studies in 9 countries. This study is designed to be part of the larger TEAM trial where the data from these 7 studies will be combined. A pre-specified analysis of the pooled data will be conducted.
Interventions
exemestane, orally, 25 mg, for 5 years
DRUGtamoxifen + exemestane
tamoxifen, 20 mg, orally, daily, 2-3 years; followed by exemestane, orally, 25 mg, for a total of 5 years of therapy
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically/cytologically confirmed adenocarcinoma of the breast, followed by adequate surgical resection and/or radiotherapy, and/or adjuvant chemotherapy, if indicated. * Stage T1-3 N0-2 Mo, Any TNM stage BC for whom adjuvant hormonal therapy is being considered.
Exclusion criteria
* Those patients not deemed to have had potentially curative primary surgical treatment or one of the following criteria: * Inflammatory breast cancer * Histologically positive supraclavicular nodes * Ulceration/infiltration of local skin metastasis * Neoadjuvant chemotherapy * Ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) without invasion * ER and PR negative primary tumor or ER/PR unknown status.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 2.75 Years | Baseline (Month 0) up to 2.75 years | Number of events (disease relapse or death) to time of observation for DFS. DFS defined as time from randomization to earliest documentation of disease relapse or death from any cause in postmenopausal, receptor positive, node negative or node positive breast cancer patients for adjuvant treatment with exemestane compared with adjuvant tamoxifen therapy at 2.75 years. Disease relapse: primary tumor recurrence (locoregional or distant) and ipsilateral or contralateral breast cancer (CBC). Intercurrent death: death without disease relapse. |
| Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 5 Years | Baseline (Month 0) up to 5 years | Number of events (disease relapse or death) to time of observation for DFS. DFS defined as time from randomization to earliest documentation of disease relapse or death from any cause in postmenopausal, receptor positive, node negative or node positive breast cancer patients for adjuvant treatment with exemestane compared with adjuvant tamoxifen therapy at 5 years. Disease relapse: primary tumor recurrence (locoregional or distant) and ipsilateral or contralateral breast cancer (CBC). Intercurrent death: death without disease relapse. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Events for Overall Survival (OS) | Baseline (Month 0) up to 5 years | Number of events (death) to time of observation for OS. OS is the duration from randomization to death. For participants who are alive, overall survival is censored at the last contact. |
| Time to New Primary Breast Cancers | Baseline (Month 0) up to 5 years | New primary breast cancers were defined as events of ipsilateral/contralateral breast cancer (CBC). |
| Number of Events for Time to Relapse | Baseline (Month 0) up to 5 years | Number of events to time of observation for relapse. Relapse is defined as all recurrences of the primary tumor (loco-regional and distant recurrence), second primary breast cancer, contralateral breast cancer. |
| Number of Participants With New Primary Non-breast Cancers | Baseline (Month 0) up to 5 years | Number of participants with new primary non-breast cancers which included colorectal cancer, lung cancer, endometrial cancer, ductal carcinoma in situ (DCIS) and other primary cancer types. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exemestane Exemestane (Aromasin®) 25 mg QD for 5 years. | 4,898 |
| Tamoxifen Followed by Exemestane Tamoxifen 20 mg QD; upon completing 2.5 years to 3 years of tamoxifen, participants were to be switched to exemestane 25 mg QD and then were to complete a total of 5 years endocrine therapy. | 4,868 |
| Total | 9,766 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomized to Study Treatment | Withdrawal by Subject | 6 | 7 |
| Study Treatment to 5 Year Report | Adverse Event | 501 | 782 |
| Study Treatment to 5 Year Report | Disease- Free Survival (DFS) event | 507 | 447 |
| Study Treatment to 5 Year Report | Intercurrent illness | 17 | 29 |
| Study Treatment to 5 Year Report | No/too late switch/refusal to switch | 0 | 750 |
| Study Treatment to 5 Year Report | Ongoing | 1,081 | 736 |
| Study Treatment to 5 Year Report | Other | 277 | 288 |
| Study Treatment to 5 Year Report | Protocol Violation | 23 | 91 |
| Study Treatment to 5 Year Report | Randomized but not treated | 46 | 54 |
| Study Treatment to 5 Year Report | Too early switch | 0 | 103 |
| Study Treatment to 5 Year Report | Treatment refusal | 113 | 208 |
Baseline characteristics
| Characteristic | Tamoxifen Followed by Exemestane | Total | Exemestane |
|---|---|---|---|
| Age, Continuous | 64 Years STANDARD_DEVIATION 9 | 64 Years STANDARD_DEVIATION 9 | 65 Years STANDARD_DEVIATION 9 |
| Age, Customized 50 to 59 years | 1507 Participants | 3017 Participants | 1510 Participants |
| Age, Customized 60 to 69 years | 1896 Participants | 3731 Participants | 1835 Participants |
| Age, Customized Greater than and equal to 70 years | 1305 Participants | 2687 Participants | 1382 Participants |
| Age, Customized Less than 50 years | 160 Participants | 331 Participants | 171 Participants |
| Sex: Female, Male Female | 4868 Participants | 9766 Participants | 4898 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 | 3,551 / 4,814 | 3,567 / 4,852 |
| serious Total, serious adverse events | 784 / 4,814 | 831 / 4,852 |
Outcome results
Primary
Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 2.75 Years
Number of events (disease relapse or death) to time of observation for DFS. DFS defined as time from randomization to earliest documentation of disease relapse or death from any cause in postmenopausal, receptor positive, node negative or node positive breast cancer patients for adjuvant treatment with exemestane compared with adjuvant tamoxifen therapy at 2.75 years. Disease relapse: primary tumor recurrence (locoregional or distant) and ipsilateral or contralateral breast cancer (CBC). Intercurrent death: death without disease relapse.
Time frame: Baseline (Month 0) up to 2.75 years
Population: Intent-to-Treat (ITT) population: participants randomized to one of the two study arms (all randomized participants); (n) = number of participants at observation for exemestane and tamoxifen, respectively. All participants were censored at 2.75 years.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exemestane | Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 2.75 Years | 352 Events (disease relapse or death) |
| Tamoxifen Followed by Exemestane | Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 2.75 Years | 388 Events (disease relapse or death) |
Comparison: Analysis at 2.75 years post-randomization. Null hypothesis: no difference in DFS between the two treatments for the first 2.75 years.~To maintain overall alpha of 0.05, 2 adjustments made: first, a nominal alpha of 0.0302 was used for the primary endpoint. Second, level of significant was 0.0012 for interim analysis.p-value: 0.11895% CI: [0.77, 1.03]Log Rank
Primary
Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 5 Years
Number of events (disease relapse or death) to time of observation for DFS. DFS defined as time from randomization to earliest documentation of disease relapse or death from any cause in postmenopausal, receptor positive, node negative or node positive breast cancer patients for adjuvant treatment with exemestane compared with adjuvant tamoxifen therapy at 5 years. Disease relapse: primary tumor recurrence (locoregional or distant) and ipsilateral or contralateral breast cancer (CBC). Intercurrent death: death without disease relapse.
Time frame: Baseline (Month 0) up to 5 years
Population: ITT population included all participants who were randomized to one of the two study arms (all randomized participants); (n) = number of participants at observation for exemestane and tamoxifen, respectively. All participants were censored at the data cut off date of 08 November 2009.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exemestane | Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 5 Years | 712 Events (disease relapse or death) |
| Tamoxifen Followed by Exemestane | Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 5 Years | 714 Events (disease relapse or death) |
Comparison: Analysis at 5 years post-randomization. Null hypothesis: no difference in DFS between the two treatments for the first 5 years.~To maintain overall alpha of 0.05, a nominal alpha of 0.0302 was used.p-value: 0.60495% CI: [0.88, 1.08]Log Rank
Secondary
Number of Events for Overall Survival (OS)
Number of events (death) to time of observation for OS. OS is the duration from randomization to death. For participants who are alive, overall survival is censored at the last contact.
Time frame: Baseline (Month 0) up to 5 years
Population: ITT population: participants randomized to one of the two study arms (all randomized participants); (n) = number of participants at observation for exemestane and tamoxifen, respectively. All participants were censored at the data cut off date of 08 November 2009.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exemestane | Number of Events for Overall Survival (OS) | 485 Events (death) |
| Tamoxifen Followed by Exemestane | Number of Events for Overall Survival (OS) | 476 Events (death) |
Comparison: Analysis at 5 years post-randomization. Null hypothesis: no difference in OS between the two treatments for the first 5 years. Overall alpha of 0.05 was maintained.p-value: 0.95195% CI: [0.89, 1.14]Log Rank
Secondary
Number of Events for Time to Relapse
Number of events to time of observation for relapse. Relapse is defined as all recurrences of the primary tumor (loco-regional and distant recurrence), second primary breast cancer, contralateral breast cancer.
Time frame: Baseline (Month 0) up to 5 years
Population: ITT population: participants randomized to one of the two study arms (all randomized participants); (n) = number of participants at observation for exemestane and tamoxifen, respectively. All participants were censored at the data cut off date of 08 November 2009.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exemestane | Number of Events for Time to Relapse | 499 Events (disease relapse) |
| Tamoxifen Followed by Exemestane | Number of Events for Time to Relapse | 521 Events (disease relapse) |
Comparison: Analysis at 5 years post-randomization. Null hypothesis: no difference in time to relapse between the two treatments for the first 5 years. Overall alpha of 0.05 was maintained.p-value: 0.29395% CI: [0.83, 1.06]Log Rank
Secondary
Number of Participants With New Primary Non-breast Cancers
Number of participants with new primary non-breast cancers which included colorectal cancer, lung cancer, endometrial cancer, ductal carcinoma in situ (DCIS) and other primary cancer types.
Time frame: Baseline (Month 0) up to 5 years
Population: ITT population: participants randomized to one of the two study arms (all randomized participants); (n) = number of participants at observation for exemestane and tamoxifen, respectively. All participants were censored at the data cut off date of 08 November 2009.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exemestane | Number of Participants With New Primary Non-breast Cancers | Lung cancer | 24 Participants |
| Exemestane | Number of Participants With New Primary Non-breast Cancers | DCIS | 3 Participants |
| Exemestane | Number of Participants With New Primary Non-breast Cancers | Endometrial cancer | 7 Participants |
| Exemestane | Number of Participants With New Primary Non-breast Cancers | Other primary cancer types | 110 Participants |
| Exemestane | Number of Participants With New Primary Non-breast Cancers | Colorectal cancer | 43 Participants |
| Tamoxifen Followed by Exemestane | Number of Participants With New Primary Non-breast Cancers | Other primary cancer types | 106 Participants |
| Tamoxifen Followed by Exemestane | Number of Participants With New Primary Non-breast Cancers | Colorectal cancer | 32 Participants |
| Tamoxifen Followed by Exemestane | Number of Participants With New Primary Non-breast Cancers | Lung cancer | 17 Participants |
| Tamoxifen Followed by Exemestane | Number of Participants With New Primary Non-breast Cancers | Endometrial cancer | 17 Participants |
| Tamoxifen Followed by Exemestane | Number of Participants With New Primary Non-breast Cancers | DCIS | 4 Participants |
Secondary
Time to New Primary Breast Cancers
New primary breast cancers were defined as events of ipsilateral/contralateral breast cancer (CBC).
Time frame: Baseline (Month 0) up to 5 years
Population: Data was not analyzed due to insufficient number of events reported for the endpoint.