Randomized Phase III Study Of Exemestane (Aromasin) For 5 Years Versus Tamoxifen for 2.5 to 3 Years Followed By Exemestane (TEAM)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00036270
First received: May 8, 2002
Last updated: March 27, 2012
Last verified: March 2012
Results First Received: October 30, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Breast Neoplasms
Interventions: Drug: exemestane (Aromasin)
Drug: tamoxifen + exemestane

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Exemestane Exemestane (Aromasin®) 25 milligram (mg) once daily (QD) for 5 years.
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.

Participant Flow for 2 periods

Period 1:   Randomized to Study Treatment
    Exemestane     Tamoxifen Followed by Exemestane  
STARTED     4904     4875  
COMPLETED     4898     4868  
NOT COMPLETED     6     7  
Withdrawal by Subject                 6                 7  

Period 2:   Study Treatment to 5 Year Report
    Exemestane     Tamoxifen Followed by Exemestane  
STARTED     4898     4868  
Treated     4852     4814  
COMPLETED     2333     1380  
NOT COMPLETED     2565     3488  
Ongoing                 1081                 736  
Disease- Free Survival (DFS) event                 507                 447  
Adverse Event                 501                 782  
Unspecified                 277                 288  
Treatment refusal                 113                 208  
Randomized but not treated                 46                 54  
Protocol Violation                 23                 91  
Intercurrent illness                 17                 29  
Too early switch                 0                 103  
No/too late switch/refusal to switch                 0                 750  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Exemestane Exemestane (Aromasin®) 25 mg QD for 5 years.
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.
Total Total of all reporting groups

Baseline Measures
    Exemestane     Tamoxifen Followed by Exemestane     Total  
Number of Participants  
[units: participants]
  4898     4868     9766  
Age  
[units: Years]
Mean ± Standard Deviation
  65  ± 9     64  ± 9     64  ± 9  
Age, Customized  
[units: Participants]
     
Less than 50 years     171     160     331  
50 to 59 years     1510     1507     3017  
60 to 69 years     1835     1896     3731  
Greater than and equal to 70 years     1382     1305     2687  
Gender  
[units: Participants]
     
Female     4898     4868     9766  
Male     0     0     0  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 2.75 Years   [ Time Frame: Baseline (Month 0) up to 2.75 years ]

Measure Type Primary
Measure Title Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 2.75 Years
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Exemestane Exemestane (Aromasin®) 25 mg QD for 5 years.
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.

Measured Values
    Exemestane     Tamoxifen Followed by Exemestane  
Number of Participants Analyzed  
[units: participants]
  4898     4868  
Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 2.75 Years  
[units: Events (disease relapse or death)]
  352     388  


Statistical Analysis 1 for Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 2.75 Years
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.118
Hazard Ratio (HR) [4] 0.89
95% Confidence Interval ( 0.77 to 1.03 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

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.

[2] Other relevant method information, such as adjustments or degrees of freedom:
  Log rank (Mantel-Cox). Adjusted for overall stratification factor; 1 degree of freedom.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  A hazard ratio less than 1 favors the test treatment (exemestane only arm).



2.  Primary:   Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 5 Years   [ Time Frame: Baseline (Month 0) up to 5 years ]

Measure Type Primary
Measure Title Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 5 Years
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Exemestane Exemestane (Aromasin®) 25 mg QD for 5 years.
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.

Measured Values
    Exemestane     Tamoxifen Followed by Exemestane  
Number of Participants Analyzed  
[units: participants]
  4898     4868  
Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 5 Years  
[units: Events (disease relapse or death)]
  712     714  


Statistical Analysis 1 for Disease Free Survival (DFS): Number of Events (Disease Relapse or Death) From Baseline up to 5 Years
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.604
Hazard Ratio (HR) [4] 0.97
95% Confidence Interval ( 0.88 to 1.08 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

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.

[2] Other relevant method information, such as adjustments or degrees of freedom:
  Log rank (Mantel-Cox). Adjusted for overall stratification factor; 1 degree of freedom.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  A hazard ratio less than 1 favors the test treatment (exemestane only arm).



3.  Secondary:   Number of Events for Overall Survival (OS)   [ Time Frame: Baseline (Month 0) up to 5 years ]

Measure Type Secondary
Measure Title Number of Events for Overall Survival (OS)
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Exemestane Exemestane (Aromasin®) 25 mg QD for 5 years.
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.

Measured Values
    Exemestane     Tamoxifen Followed by Exemestane  
Number of Participants Analyzed  
[units: participants]
  4898     4868  
Number of Events for Overall Survival (OS)  
[units: Events (death)]
  485     476  


Statistical Analysis 1 for Number of Events for Overall Survival (OS)
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.951
Hazard Ratio (HR) [4] 1.00
95% Confidence Interval ( 0.89 to 1.14 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Log rank (Mantel-Cox). Adjusted for overall stratification factor; 1 degree of freedom.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  A hazard ratio less than 1 favors the test treatment (exemestane only arm).



4.  Secondary:   Time to New Primary Breast Cancers   [ Time Frame: Baseline (Month 0) up to 5 years ]

Measure Type Secondary
Measure Title Time to New Primary Breast Cancers
Measure Description New primary breast cancers were defined as events of ipsilateral/contralateral breast cancer (CBC).
Time Frame Baseline (Month 0) up to 5 years  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data was not analyzed due to insufficient number of events reported for the endpoint.

Reporting Groups
  Description
Exemestane Exemestane (Aromasin®) 25 mg QD for 5 years.
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.

Measured Values
    Exemestane     Tamoxifen Followed by Exemestane  
Number of Participants Analyzed  
[units: participants]
  0     0  
Time to New Primary Breast Cancers  
[units: Years]
       

No statistical analysis provided for Time to New Primary Breast Cancers



5.  Secondary:   Number of Events for Time to Relapse   [ Time Frame: Baseline (Month 0) up to 5 years ]

Measure Type Secondary
Measure Title Number of Events for Time to Relapse
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Exemestane Exemestane (Aromasin®) 25 mg QD for 5 years.
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.

Measured Values
    Exemestane     Tamoxifen Followed by Exemestane  
Number of Participants Analyzed  
[units: participants]
  4898     4868  
Number of Events for Time to Relapse  
[units: Events (disease relapse)]
  499     521  


Statistical Analysis 1 for Number of Events for Time to Relapse
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.293
Hazard Ratio (HR) [4] 0.94
95% Confidence Interval ( 0.83 to 1.06 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Log rank (Mantel-Cox). Adjusted for overall stratification factor; 1 degree of freedom.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  A hazard ratio less than 1 favors the test treatment (exemestane only arm).



6.  Secondary:   Number of Participants With New Primary Non-breast Cancers   [ Time Frame: Baseline (Month 0) up to 5 years ]

Measure Type Secondary
Measure Title Number of Participants With New Primary Non-breast Cancers
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Exemestane Exemestane (Aromasin®) 25 mg QD for 5 years.
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.

Measured Values
    Exemestane     Tamoxifen Followed by Exemestane  
Number of Participants Analyzed  
[units: participants]
  4898     4868  
Number of Participants With New Primary Non-breast Cancers  
[units: Participants]
   
Colorectal cancer     43     32  
Lung cancer     24     17  
Endometrial cancer     7     17  
DCIS     3     4  
Other primary cancer types     110     106  

No statistical analysis provided for Number of Participants With New Primary Non-breast Cancers




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Overall Survival was reported as number of events which otherwise reported as time.


  More Information