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Efficacy and Safety Study of Enzalutamide in Combination With Exemestane in Patients With Advanced Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02007512
Recruitment Status : Active, not recruiting
First Posted : December 10, 2013
Results First Posted : February 6, 2018
Last Update Posted : April 26, 2024
Sponsor:
Collaborators:
Astellas Pharma Inc
Medivation, Inc.
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: Enzalutamide
Drug: exemestane
Drug: Placebo (for enzalutamide)
Enrollment 247
Recruitment Details  
Pre-assignment Details This was a phase 2, randomized, double blind, placebo-controlled study. The results disclosed in this draft were based on the data collected till 23 Sep 2016.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first. Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first. Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first. Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Period Title: Double Blind Treatment Period
Started 63 64 60 60
Treated 62 63 60 60
Completed 0 0 0 0
Not Completed 63 64 60 60
Reason Not Completed
Adverse Event             4             2             6             2
Death             1             0             0             0
Disease progression             44             49             45             51
Withdrawal by Subject             4             2             3             3
Protocol Violation             0             0             0             1
Other             0             0             1             2
Ongoing as of data cutoff (23 Sep 2016)             10             11             5             1
Period Title: Open Label Treatment Period
Started 0 21 [1] 0 12 [2]
Completed 0 0 0 0
Not Completed 0 21 0 12
Reason Not Completed
Adverse Event             0             1             0             0
Other             0             0             0             1
Disease progression             0             17             0             11
Ongoing as of data cutoff (23 Sep 2016)             0             3             0             0
[1]
Of the participants with disease progression in double blind period, 21 entered open label period.
[2]
Of the participants with disease progression in double blind period, 12 entered open label period.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg Total
Hide Arm/Group Description Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first. Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first. Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first. Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first. Total of all reporting groups
Overall Number of Baseline Participants 63 64 60 60 247
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all the participants randomly assigned to double-blind study treatment.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 64 participants 60 participants 60 participants 247 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
42
  66.7%
32
  50.0%
37
  61.7%
40
  66.7%
151
  61.1%
>=65 years
21
  33.3%
32
  50.0%
23
  38.3%
20
  33.3%
96
  38.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 64 participants 60 participants 60 participants 247 participants
Female
63
 100.0%
64
 100.0%
60
 100.0%
60
 100.0%
247
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Progression Free Survival (PFS): Intent-to-Treat (ITT) Population By Interactive Web Recognition System (IWRS)
Hide Description PFS was defined as the time in months from randomization to the first documentation of progression of disease (PD) or death on study due to any cause, whichever occurred first. PD according to response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) was defined as greater than or equal to (>=) 20 percent (%) increase in the sum of diameters of the target lesions taking as a reference the smallest sum recorded since the start of treatment or unequivocal progression in non-target lesions or the appearance of 1 or more new lesions. The analysis of PFS was based on investigator assessment of disease progression. Participants who were not known to have had a PFS event at the analysis date were censored at last tumor assessment date prior to data cutoff or date of new treatment initiation, whichever occurred first.
Time Frame From randomization until PD, last tumor assessment without PD before new antitumor treatment initiation or death due to any cause, whichever occurred first (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the participants randomly assigned to double-blind study treatment.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description:
Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 63 64 60 60
Median (95% Confidence Interval)
Unit of Measure: months
11.8
(7.3 to 15.9)
5.8
(3.5 to 10.9)
3.6
(1.9 to 5.5)
3.9
(2.6 to 5.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg, Cohort 1: Placebo + Exemestane 25 mg
Comments Hazard ratio was based on stratified Cox regression model.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3631
Comments [Not Specified]
Method Stratified log-rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.820
Confidence Interval (2-Sided) 95%
0.535 to 1.257
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg, Cohort 2: Placebo + Exemestane 25 mg
Comments Hazard ratio was based on stratified Cox regression model.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9212
Comments [Not Specified]
Method Stratified log-rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.022
Confidence Interval (2-Sided) 95%
0.659 to 1.586
Estimation Comments [Not Specified]
2.Primary Outcome
Title Progression Free Survival (PFS): Diagnostic Positive (DX+) Population By Interactive Web Recognition System (IWRS)
Hide Description PFS was defined as the time in months from randomization to the first documentation of PD or death on study due to any cause, whichever occurred first. PD according to RECIST 1.1, was defined as >= 20% increase in the sum of diameters of the target lesions taking as a reference the smallest sum recorded since the start of treatment or unequivocal progression in non-target lesions or the appearance of 1 or more new lesions. The analysis of PFS was based on investigator assessment of disease progression. Participants who were not known to have had a PFS event at the analysis date were censored at last tumor assessment date prior to data cutoff or date of new treatment initiation, whichever occurred first.
Time Frame From randomization until PD, last tumor assessment without PD before new antitumor treatment initiation or death due to any cause, whichever occurred first (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Dx+ population: Subset of ITT population, defined prior to the first unblinded analysis as meeting the threshold for diagnostic score based on ribonucleic acid (RNA) sequencing data from tumor tissue. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description:
Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 24 26 15 20
Median (95% Confidence Interval)
Unit of Measure: months
16.5 [1] 
(11.0 to NA)
4.3
(1.9 to 10.9)
6.0
(2.3 to 26.7)
5.3
(1.8 to 6.7)
[1]
Upper limit of 95% confidence interval was not reached due to insufficient number of events at the time of data cutoff (23 Sep 2016).
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg, Cohort 1: Placebo + Exemestane 25 mg
Comments Hazard ratio was based on stratified Cox regression model.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0335
Comments [Not Specified]
Method Stratified log-rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.442
Confidence Interval (2-Sided) 95%
0.205 to 0.955
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg, Cohort 2: Placebo + Exemestane 25 mg
Comments Hazard ratio was based on stratified Cox regression model.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1936
Comments [Not Specified]
Method Stratified log-rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.554
Confidence Interval (2-Sided) 95%
0.225 to 1.363
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Clinical Benefit Rate-24 (CBR-24)
Hide Description CBR-24: Percentage of participants with a best response of complete response (CR), partial response (PR), or stable disease (SD) sustained for atleast 24 weeks, as determined by investigator using RECIST 1.1. CR: Disappearance of all (target and non-target) lesions and normalization of tumor marker level for non-target lesions. All lymph nodes (target and non-target) must be non-pathological in size (less than [<] 10 millimeter [mm] short axis). PR: >=30% decrease in sum of diameters of target lesions, using baseline sum diameters as reference. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during study as reference. PD: >=20% increase (an absolute increase of >=5 mm) in sum of diameters of target lesions, using the smallest sum during the study as a reference (including baseline sum), or unequivocal progression of existing non-target lesions, or appearance of atleast 1 new target or non-target lesions.
Time Frame From randomization up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the participants randomly assigned to double-blind study treatment.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description:
Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 63 64 60 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
61.9
(48.8 to 73.9)
45.3
(32.8 to 58.3)
20.0
(10.8 to 32.3)
31.7
(20.3 to 45.0)
4.Secondary Outcome
Title Best Objective Response Rate
Hide Description Best objective response rate: Percentage of participants with measurable disease and with a best response of CR or PR according to RECIST 1.1. CR: Disappearance of all (target and non-target) lesions and normalization of tumor marker level for non-target lesions. All lymph nodes (target and non-target) must be non-pathological in size (<10 mm short axis). PR: Atleast 30% decrease in sum of diameters of target lesions, using baseline sum diameters as reference. Response evaluation was based on investigators' judgment.
Time Frame From randomization until CR or PR, whichever occurred first (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the participants randomly assigned to double-blind study treatment. Here 'Number of participants analyzed' signifies participants with measurable response.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description:
Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 39 42 42 42
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
30.8
(17.0 to 47.6)
19.0
(8.6 to 34.1)
9.5
(2.7 to 22.6)
4.8
(0.6 to 16.2)
5.Secondary Outcome
Title Duration of Objective Response
Hide Description Duration of objective response: Time from first documentation of CR or PR, to the first documentation of PD or death due to any cause, whichever occurred first as determined by investigator using RECIST 1.1. CR: Disappearance of all (target and non-target) lesions and normalization of tumor marker level for non-target lesions. All lymph nodes (target and non-target) must be non-pathological in size (<10 mm short axis). PR: >=30% decrease in sum of diameters of target lesions, using baseline sum diameters as reference. PD: >=20% increase (an absolute increase of >=5 mm) in sum of diameters of target lesions, using the smallest sum during the study as a reference (including baseline sum), or unequivocal progression of existing non-target lesions, or appearance of atleast 1 new target or non-target lesions. Participants with no PD or death (after initial CR or PR) at the analysis date were censored at last tumor assessment date prior to date of new antitumor treatment or data cutoff.
Time Frame From first documentation of CR or PR until PD, or last tumor assessment without PD before new antitumor treatment initiation or death due to any cause, whichever occurred first (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the participants randomly assigned to double-blind study treatment. Here 'Number of participants analyzed' signifies participants evaluable for this outcome measure.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description:
Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 39 42 42 42
Median (95% Confidence Interval)
Unit of Measure: months
14.0 [1] 
(5.6 to NA)
9.1
(3.2 to 10.2)
18.3
(3.3 to 23.1)
4.6
(1.9 to 7.4)
[1]
Upper limit of 95% confidence interval was not reached due to insufficient number of events at the time of data cutoff (23 Sep 2016).
6.Secondary Outcome
Title Time to Response
Hide Description Time to response: Time from randomization to first documentation of CR or PR. CR: Disappearance of all (target and non-target) lesions and normalization of tumor marker level for non-target lesions. All lymph nodes (target and non-target) must be non-pathological in size (<10 mm short axis). PR: >=30% decrease in sum of diameters of target lesions, using baseline sum diameters as reference. PD: >=20% increase (an absolute increase of >=5 mm) in sum of diameters of target lesions, using the smallest sum during the study as a reference (including baseline sum), or unequivocal progression of existing non-target lesions, or appearance of atleast 1 new target or non-target lesions. Participants who were not known to have had a CR or PR were censored at last tumor assessment date prior to data cutoff or date of new treatment initiation, whichever occurred first.
Time Frame From randomization until first documentation of CR or PR, or last tumor assessment without PD or death prior to new antitumor treatment initiation, whichever occurred first (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the participants randomly assigned to double-blind study treatment. Here 'Number of participants analyzed' signifies participants evaluable for this outcome measure.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description:
Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 39 42 42 42
Median (95% Confidence Interval)
Unit of Measure: months
12.9 [1] 
(7.3 to NA)
14.0 [1] 
(7.4 to NA)
NA [2] 
(3.9 to NA)
NA [3] 
(NA to NA)
[1]
Upper limit of 95% confidence interval was not reached due to insufficient number of events at the time of data cutoff (23 Sep 2016).
[2]
Median and upper limit of 95% confidence interval were not reached due to insufficient number of events at the time of data cutoff (23 Sep 2016).
[3]
Median and 95% confidence interval were not reached due to insufficient number of events at the time of data cutoff (23 Sep 2016).
7.Secondary Outcome
Title Time to Progression
Hide Description Time to progression was defined as the time from the date of randomization to PD defined by the investigator using RECIST 1.1. PD: >=20% increase (an absolute increase of >=5 mm) in sum of diameters of target lesions, using the smallest sum during the study as a reference (including baseline sum), or unequivocal progression of existing non-target lesions, or appearance of atleast 1 new target or non-target lesions. Participants who did not experience disease progression, time to progression was right censored at the date of the last tumor assessment prior to data cutoff or date of new antitumor treatment, whichever occurred first.
Time Frame From randomization until PD or last tumor assessment without PD before new antitumor treatment initiation, whichever occurred first (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the participants randomly assigned to double-blind study treatment.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description:
Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 63 64 60 60
Median (95% Confidence Interval)
Unit of Measure: months
11.8
(7.3 to 15.9)
7.4
(3.5 to 13.5)
3.6
(1.9 to 5.6)
3.9
(2.6 to 5.4)
8.Secondary Outcome
Title Progression Free Survival (PFS) at 6 Months
Hide Description PFS at 6 months was defined as the percentage of participants with no event of disease progression at Month 6 landmark, estimated by Kaplan-Meier methods. PFS was defined as the time in months from randomization to the first documentation of PD or death on study due to any cause, whichever occurred first. PD: >=20% increase (an absolute increase of >=5 mm) in sum of diameters of target lesions, using the smallest sum during the study as a reference (including baseline sum), or unequivocal progression of existing non-target lesions, or appearance of atleast 1 new target or non-target lesions. The analysis of PFS was based on investigator assessment of disease progression.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the participants randomly assigned to double-blind study treatment.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description:
Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 63 64 60 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
66.7
(53.2 to 77.0)
50.0
(37.1 to 61.6)
31.5
(19.7 to 43.9)
33.3
(21.6 to 45.5)
9.Secondary Outcome
Title Concentration Versus Time Summary of Enzalutamide
Hide Description Concentration versus time summary was calculated by setting concentration values below limit of quantitation to zero.
Time Frame Predose on Day 29, 57 and 113
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population for enzalutamide included all participants in safety population who received any amount of enzalutamide and had at least 1 reportable concentration value for enzalutamide or its active metabolite (N-desmethyl enzalutamide).
Arm/Group Title Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received enzalutamide 160 mg dose orally, once daily, either in double blind treatment period or in open label treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after the last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 114
Mean (Standard Deviation)
Unit of Measure: microgram per milliliter
Day 29 Number Analyzed 109 participants
14.2  (2.97)
Day 57 Number Analyzed 92 participants
14.2  (3.21)
Day 113 Number Analyzed 67 participants
13.2  (4.51)
10.Secondary Outcome
Title Concentration Versus Time Summary of Exemestane
Hide Description Concentration versus time summary was calculated by setting concentration values below limit of quantitation to zero.
Time Frame Predose, 1 and 6 hour postdose on Day 29, 57, 113 and 169
Hide Outcome Measure Data
Hide Analysis Population Description
PK population for exemestane was defined as all participants in the safety population who received any amount of exemestane and had at least 1 reportable plasma concentration value for exemestane.
Arm/Group Title Exemestane 25 mg Exemestane 50 mg
Hide Arm/Group Description:
Participants received exemestane 25 mg dose orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after the last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants received exemestane 50 mg dose orally, once daily until disease progression or permanent treatment discontinuation, either in double blind treatment period or in open label treatment period. Participants were followed-up until 30 days after the last dose of study drug, the date of death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 114 115
Mean (Standard Deviation)
Unit of Measure: Picogram per milliliter
Day 29: Predose Number Analyzed 108 participants 108 participants
1010  (1600) 943  (939)
Day 29: 1 hour Postdose Number Analyzed 99 participants 102 participants
17000  (16400) 19200  (17800)
Day 29: 6 hour Postdose Number Analyzed 57 participants 55 participants
5590  (4750) 6850  (9090)
Day 57: Predose Number Analyzed 89 participants 92 participants
1160  (2590) 1100  (2650)
Day 57: 1 hour Postdose Number Analyzed 76 participants 83 participants
19900  (18600) 15300  (14500)
Day 57: 6 hour Postdose Number Analyzed 26 participants 23 participants
5890  (4880) 5650  (6200)
Day 113: Predose Number Analyzed 65 participants 68 participants
1160  (2870) 1330  (3380)
Day 113: 1 hour Postdose Number Analyzed 58 participants 58 participants
20800  (18100) 19400  (18500)
Day 113: 6 hour Postdose Number Analyzed 12 participants 14 participants
3510  (3850) 5600  (5290)
Day 169: Predose Number Analyzed 0 participants 0 participants
Day 169: 1 hour Postdose Number Analyzed 0 participants 1 participants
22800 [1]   (NA)
Day 169: 6 hour Postdose Number Analyzed 0 participants 1 participants
6020 [1]   (NA)
[1]
Standard deviation could not be estimated since only 1 participant was analyzed.
11.Secondary Outcome
Title Concentration Versus Time Summary of N-desmethyl Enzalutamide
Hide Description N-desmethyl enzalutamide was the active metabolite of enzalutamide. Concentration versus time summary was calculated by setting concentration values below limit of quantitation to zero.
Time Frame Predose on Day 29, 57 and 113
Hide Outcome Measure Data
Hide Analysis Population Description
PK population for N-desmethyl enzalutamide included all the participants in safety population who received any amount of enzalutamide and had at least 1 reportable concentration value for N-desmethyl enzalutamide.
Arm/Group Title Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received enzalutamide 160 mg dose orally, once daily, either in double blind treatment period or in open label treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after the last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 114
Mean (Standard Deviation)
Unit of Measure: microgram per milliliter
Day 29 Number Analyzed 109 participants
11.6  (4.10)
Day 57 Number Analyzed 92 participants
15.2  (4.76)
Day 113 Number Analyzed 67 participants
15.2  (5.81)
12.Other Pre-specified Outcome
Title European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Core Questionnaire (QLQ-C30)
Hide Description [Not Specified]
Time Frame Month 24
Outcome Measure Data Not Reported
13.Other Pre-specified Outcome
Title European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer Module (QLQ-BR23)
Hide Description [Not Specified]
Time Frame Month 24
Outcome Measure Data Not Reported
14.Other Pre-specified Outcome
Title Number of Participants With Positive Androgen Receptor (AR) Expression by Immunohistochemistry (IHC)
Hide Description [Not Specified]
Time Frame Day 1, 29, 57, 113 and 169
Hide Outcome Measure Data
Hide Analysis Population Description
Protocol of this study was amended and data for this outcome measure was not analyzed as per planned analysis.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description:
Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
15.Other Pre-specified Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious AEs.
Time Frame Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all the participants who received study drug either in double blind or in open label treatment period.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description:
Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 62 63 60 60
Measure Type: Number
Unit of Measure: participants
AEs 59 58 58 53
SAEs 15 12 10 8
16.Other Pre-specified Outcome
Title Number of Participants With Treatment-Emergent Adverse Events of Grade 3 or Higher Severity
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of the AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Only the participants with treatment-emergent AEs of grade 3 (severe) or higher grade were reported in this outcome measure.
Time Frame Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all the participants who received study drug either in double blind or in open label treatment period.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description:
Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 62 63 60 60
Measure Type: Number
Unit of Measure: participants
20 15 22 12
17.Other Pre-specified Outcome
Title Number of Participants With Clinically Significant Vital Sign Abnormalities
Hide Description Criteria for clinically significant vital sign abnormalities: Systolic blood pressure (SBP): absolute SBP <90 millimeters of mercury (mmHg) and decrease from baseline (DFB) >30 mmHg, absolute SBP>180 mmHg and increase from baseline (IFB) >40 mmHg, final visit or 2 consecutive visits SBP >=20 mmHg change from baseline (CFB), most extreme post-baseline SBP >=140 mmHg, most extreme post-baseline SBP >=180 mmHg, most extreme SBP >=140 mmHg and >=20 mmHg CFB, most extreme SBP >=180 mmHg and >=20 mmHg CFB; diastolic blood pressure (DBP): absolute DBP > 105 mmHg and IFB >30 mmHg, absolute DBP <50 mmHg and DFB >20 mmHg, final visit or 2 consecutive visits DBP >=15 mmHg CFB, most extreme post-baseline DBP >=90 mmHg, most extreme post-baseline DBP >=105 mmHg, most extreme DBP >=90 mmHg and >=15 mmHg CFB, most extreme DBP >=105 mmHg and >=15 mmHg CFB; heart rate <50 beats per minute (BPM) and DFB >20 BPM or heart rate >120 BPM and IFB >30 BPM.
Time Frame Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all the participants who received study drug either in double blind or in open label treatment period.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description:
Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 62 63 60 60
Measure Type: Number
Unit of Measure: participants
Blood pressure 36 39 43 24
Heart rate 0 2 0 0
18.Other Pre-specified Outcome
Title Number of Participants With Clinically Significant Laboratory Abnormalities
Hide Description Laboratory tests included hematology (hematocrit, hemoglobin, platelet count, red blood cell count, total neutrophils [absolute] and white blood cell count with differential) and serum chemistry (albumin, alkaline phosphatase, alanine aminotransferase [ALT], aspartate transaminase [AST], blood urea nitrogen and creatinine, calcium, sodium, potassium, chloride, glucose (non-fasting), lactate dehydrogenase, magnesium, phosphorus/phosphate, total bilirubin, total bicarbonate, total protein and uric acid). Clinically significant abnormality evaluation was based on clinical investigator's judgment.
Time Frame Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all the participants who received study drug either in double blind or in open label treatment period.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description:
Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 62 63 60 60
Measure Type: Number
Unit of Measure: participants
0 0 0 0
19.Other Pre-specified Outcome
Title Progression Free Survival (PFS): By Electronic Data Capture (EDC)
Hide Description PFS was defined as the time in months from randomization to the first documentation of PD or death on study due to any cause, whichever occurred first. PD according to RECIST 1.1 was defined >=20 % increase in the sum of diameters of the target lesions taking as a reference the smallest sum recorded since the start of treatment or unequivocal progression in non-target lesions or the appearance of 1 or more new lesions. The analysis of PFS was based on investigator assessment of disease progression. Participants who were not known to have had a PFS event at the analysis date were censored at last tumor assessment date prior to data cutoff or date of new treatment initiation, whichever occurred first. Cht 1: Enz + Exe = Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg; Cht 2: Enz + Exe= Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg
Time Frame From randomization until PD, last tumor assessment without PD before new antitumor treatment initiation or death due to any cause, whichever occurred first (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on all randomized participants. Randomization to cohort was based on participant's exposure to advance setting hormonal therapy. Initial randomization was done by IWRS. Later, upon detailed data entry in EDC, it was determined 1 participant was incorrectly assigned to Cht1:Enz+Exe by IWRS,hence counted in Cht2:Enz+Exe by EDC.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description:
Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 62 64 61 60
Median (95% Confidence Interval)
Unit of Measure: months
11.8
(7.3 to 14.6)
5.8
(3.5 to 10.9)
3.6
(1.9 to 5.6)
3.9
(2.6 to 5.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg, Cohort 1: Placebo + Exemestane 25 mg
Comments Hazard ratio was based on stratified Cox regression model.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7378
Comments [Not Specified]
Method Stratified log-rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.928
Confidence Interval (2-Sided) 95%
0.599 to 1.438
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg, Cohort 2: Placebo + Exemestane 25 mg
Comments Hazard ratio was based on stratified Cox regression model.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8817
Comments [Not Specified]
Method Stratified log-rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.968
Confidence Interval (2-Sided) 95%
0.632 to 1.483
Estimation Comments [Not Specified]
20.Other Pre-specified Outcome
Title Progression Free Survival (PFS): Diagnostic Positive (DX+) Population By Electronic Data Capture (EDC)
Hide Description PFS was defined as the time in months from randomization to the first documentation of PD or death on study due to any cause, whichever occurred first. PD according to RECIST 1.1, was defined as >= 20% increase in the sum of diameters of the target lesions taking as a reference the smallest sum recorded since the start of treatment or unequivocal progression in non-target lesions or the appearance of 1 or more new lesions. The analysis of PFS was based on investigator assessment of disease progression. Participants who were not known to have had a PFS event at the analysis date were censored at last tumor assessment date prior to data cutoff or date of new treatment initiation, whichever occurred first.
Time Frame From randomization until PD, last tumor assessment without PD before new antitumor treatment initiation or death due to any cause, whichever occurred first (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Dx+ population: Subset of ITT population, defined prior to the first unblinded analysis as meeting the threshold for diagnostic score based on ribonucleic acid (RNA) sequencing data from tumor tissue. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description:
Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
Overall Number of Participants Analyzed 23 26 16 20
Median (95% Confidence Interval)
Unit of Measure: months
16.9 [1] 
(11.0 to NA)
4.3
(1.9 to 10.9)
6.0
(3.5 to 16.6)
5.3
(1.8 to 6.7)
[1]
Upper limit of 95% confidence interval was not reached due to insufficient number of events at the time of data cutoff (23 Sep 2016).
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg, Cohort 1: Placebo + Exemestane 25 mg
Comments Hazard ratio was based on stratified Cox regression model.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1270
Comments [Not Specified]
Method Stratified log-rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.522
Confidence Interval (2-Sided) 95%
0.224 to 1.217
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg, Cohort 2: Placebo + Exemestane 25 mg
Comments Hazard ratio was based on stratified Cox regression model.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0359
Comments [Not Specified]
Method Stratified log-rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.370
Confidence Interval (2-Sided) 95%
0.143 to 0.961
Estimation Comments [Not Specified]
Time Frame Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first (up to 3 years)
Adverse Event Reporting Description Same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. AEs and SAEs were collected for safety population.
 
Arm/Group Title Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Hide Arm/Group Description Participants with no previous hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first. Participants with no previous hormonal treatment for advanced breast cancer received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first. Participants with previous disease progression following hormonal treatment for advanced breast cancer, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first. Participants with previous disease progression following hormonal treatment for advanced breast cancer, received placebo matched to enzalutamide along with exemestane 25 mg, orally, once daily in double blind treatment period until disease progression or permanent treatment discontinuation. Eligible participants with disease progression in double blind period, on their discretion, received enzalutamide 160 mg along with exemestane 50 mg, orally, once daily up to disease progression in open label treatment period. Participants were followed-up until 30 days after last dose of study drug, death, or before initiation of a new antitumor treatment, whichever occurred first.
All-Cause Mortality
Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/62 (24.19%)   12/63 (19.05%)   10/60 (16.67%)   8/60 (13.33%) 
Blood and lymphatic system disorders         
ANAEMIA * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
THROMBOCYTOPENIA * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
Cardiac disorders         
CARDIAC FAILURE CONGESTIVE * 1  0/62 (0.00%)  0/63 (0.00%)  0/60 (0.00%)  1/60 (1.67%) 
Gastrointestinal disorders         
FAECES DISCOLOURED * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  0/60 (0.00%) 
GASTROINTESTINAL HAEMORRHAGE * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
INTESTINAL OBSTRUCTION * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
OESOPHAGEAL STENOSIS * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  0/60 (0.00%) 
VOMITING * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
General disorders         
ASTHENIA * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
CHILLS * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
DISEASE PROGRESSION * 1  0/62 (0.00%)  1/63 (1.59%)  1/60 (1.67%)  0/60 (0.00%) 
FACIAL PAIN * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
FATIGUE * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
GENERAL PHYSICAL HEALTH DETERIORATION * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
INFLUENZA LIKE ILLNESS * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
NON-CARDIAC CHEST PAIN * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
PAIN * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
Hepatobiliary disorders         
CHOLECYSTITIS * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
HEPATIC HAEMORRHAGE * 1  0/62 (0.00%)  0/63 (0.00%)  0/60 (0.00%)  1/60 (1.67%) 
Immune system disorders         
ANAPHYLACTIC REACTION * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
DRUG HYPERSENSITIVITY * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
Infections and infestations         
BREAST CELLULITIS * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
PNEUMONIA * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
POSTOPERATIVE WOUND INFECTION * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
PYELONEPHRITIS * 1  0/62 (0.00%)  0/63 (0.00%)  0/60 (0.00%)  1/60 (1.67%) 
URINARY TRACT INFECTION * 1  0/62 (0.00%)  0/63 (0.00%)  0/60 (0.00%)  1/60 (1.67%) 
WOUND INFECTION * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  0/60 (0.00%) 
Injury, poisoning and procedural complications         
FALL * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  0/60 (0.00%) 
HUMERUS FRACTURE * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  1/60 (1.67%) 
LACERATION * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  0/60 (0.00%) 
OPTIC NERVE INJURY * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
RADIATION PNEUMONITIS * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  0/60 (0.00%) 
SPINAL COMPRESSION FRACTURE * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
TRAUMATIC HAEMORRHAGE * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  0/60 (0.00%) 
Metabolism and nutrition disorders         
HYPERCALCAEMIA * 1  2/62 (3.23%)  0/63 (0.00%)  2/60 (3.33%)  1/60 (1.67%) 
HYPONATRAEMIA * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
HYPOPHOSPHATAEMIA * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
Musculoskeletal and connective tissue disorders         
BACK PAIN * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  1/60 (1.67%) 
MASTICATION DISORDER * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
NECK PAIN * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
PAIN IN EXTREMITY * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
PATHOLOGICAL FRACTURE * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
ADENOCARCINOMA PANCREAS * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
BREAST CANCER * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  0/60 (0.00%) 
BREAST CANCER METASTATIC * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  0/60 (0.00%) 
CONTRALATERAL BREAST CANCER * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
LYMPHANGIOSIS CARCINOMATOSA * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  0/60 (0.00%) 
MALIGNANT ASCITES * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
MALIGNANT PLEURAL EFFUSION * 1  2/62 (3.23%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
METASTASES TO CENTRAL NERVOUS SYSTEM * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
METASTATIC PAIN * 1  1/62 (1.61%)  1/63 (1.59%)  1/60 (1.67%)  0/60 (0.00%) 
PLASMA CELL MYELOMA * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  0/60 (0.00%) 
Nervous system disorders         
BRACHIAL PLEXOPATHY * 1  0/62 (0.00%)  0/63 (0.00%)  0/60 (0.00%)  1/60 (1.67%) 
CEREBROVASCULAR ACCIDENT * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
DIZZINESS * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
EMBOLIC STROKE * 1  0/62 (0.00%)  0/63 (0.00%)  0/60 (0.00%)  1/60 (1.67%) 
GRAND MAL CONVULSION * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
HAEMORRHAGE INTRACRANIAL * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  0/60 (0.00%) 
INTRACRANIAL HAEMATOMA * 1  0/62 (0.00%)  0/63 (0.00%)  0/60 (0.00%)  1/60 (1.67%) 
SPEECH DISORDER * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
SPINAL CORD COMPRESSION * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  0/60 (0.00%) 
STATUS EPILEPTICUS * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
SYNCOPE * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
Psychiatric disorders         
DELIRIUM * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  0/60 (0.00%) 
SUICIDAL IDEATION * 1  0/62 (0.00%)  0/63 (0.00%)  0/60 (0.00%)  1/60 (1.67%) 
Renal and urinary disorders         
RENAL FAILURE * 1  0/62 (0.00%)  0/63 (0.00%)  0/60 (0.00%)  1/60 (1.67%) 
Respiratory, thoracic and mediastinal disorders         
DYSPNOEA * 1  1/62 (1.61%)  1/63 (1.59%)  0/60 (0.00%)  1/60 (1.67%) 
DYSPNOEA EXERTIONAL * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  0/60 (0.00%) 
PLEURAL EFFUSION * 1  0/62 (0.00%)  1/63 (1.59%)  0/60 (0.00%)  1/60 (1.67%) 
PULMONARY EMBOLISM * 1  1/62 (1.61%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1: Enzalutamide 160 mg + Exemestane 50 mg Cohort 1: Placebo + Exemestane 25 mg Cohort 2: Enzalutamide 160 mg + Exemestane 50 mg Cohort 2: Placebo + Exemestane 25 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   59/62 (95.16%)   58/63 (92.06%)   58/60 (96.67%)   53/60 (88.33%) 
Blood and lymphatic system disorders         
ANAEMIA * 1  4/62 (6.45%)  1/63 (1.59%)  6/60 (10.00%)  3/60 (5.00%) 
Gastrointestinal disorders         
CONSTIPATION * 1  10/62 (16.13%)  7/63 (11.11%)  8/60 (13.33%)  8/60 (13.33%) 
DIARRHOEA * 1  12/62 (19.35%)  10/63 (15.87%)  6/60 (10.00%)  10/60 (16.67%) 
DYSPEPSIA * 1  1/62 (1.61%)  6/63 (9.52%)  5/60 (8.33%)  4/60 (6.67%) 
NAUSEA * 1  24/62 (38.71%)  10/63 (15.87%)  18/60 (30.00%)  11/60 (18.33%) 
VOMITING * 1  11/62 (17.74%)  7/63 (11.11%)  6/60 (10.00%)  3/60 (5.00%) 
ABDOMINAL PAIN UPPER * 1  0/62 (0.00%)  0/63 (0.00%)  4/60 (6.67%)  2/60 (3.33%) 
ABDOMINAL PAIN * 1  0/62 (0.00%)  0/63 (0.00%)  2/60 (3.33%)  4/60 (6.67%) 
General disorders         
ASTHENIA * 1  10/62 (16.13%)  7/63 (11.11%)  6/60 (10.00%)  4/60 (6.67%) 
FATIGUE * 2  23/62 (37.10%)  21/63 (33.33%)  22/60 (36.67%)  13/60 (21.67%) 
OEDEMA PERIPHERAL * 1  0/62 (0.00%)  0/63 (0.00%)  2/60 (3.33%)  3/60 (5.00%) 
PAIN * 1  0/62 (0.00%)  0/63 (0.00%)  0/60 (0.00%)  3/60 (5.00%) 
PYREXIA * 1  0/62 (0.00%)  0/63 (0.00%)  0/60 (0.00%)  3/60 (5.00%) 
Infections and infestations         
URINARY TRACT INFECTION * 1  0/62 (0.00%)  0/63 (0.00%)  1/60 (1.67%)  4/60 (6.67%) 
NASOPHARYNGITIS * 1  0/62 (0.00%)  0/63 (0.00%)  3/60 (5.00%)  1/60 (1.67%) 
UPPER RESPIRATORY TRACT INFECTION * 1  2/62 (3.23%)  4/63 (6.35%)  1/60 (1.67%)  3/60 (5.00%) 
INFLUENZA * 1  2/62 (3.23%)  4/63 (6.35%)  0/60 (0.00%)  0/60 (0.00%) 
Investigations         
ALANINE AMINOTRANSFERASE INCREASED * 1  0/62 (0.00%)  0/63 (0.00%)  2/60 (3.33%)  4/60 (6.67%) 
ASPARTATE AMINOTRANSFERASE INCREASED * 1  0/62 (0.00%)  4/63 (6.35%)  2/60 (3.33%)  3/60 (5.00%) 
WHITE BLOOD CELL COUNT DECREASED * 1  0/62 (0.00%)  0/63 (0.00%)  3/60 (5.00%)  1/60 (1.67%) 
Metabolism and nutrition disorders         
DECREASED APPETITE * 1  6/62 (9.68%)  6/63 (9.52%)  6/60 (10.00%)  2/60 (3.33%) 
Musculoskeletal and connective tissue disorders         
ARTHRALGIA * 1  14/62 (22.58%)  11/63 (17.46%)  10/60 (16.67%)  7/60 (11.67%) 
BACK PAIN * 1  11/62 (17.74%)  5/63 (7.94%)  4/60 (6.67%)  12/60 (20.00%) 
BONE PAIN * 1  2/62 (3.23%)  4/63 (6.35%)  5/60 (8.33%)  2/60 (3.33%) 
MUSCULOSKELETAL CHEST PAIN * 1  7/62 (11.29%)  4/63 (6.35%)  2/60 (3.33%)  3/60 (5.00%) 
MUSCULOSKELETAL PAIN * 1  7/62 (11.29%)  1/63 (1.59%)  0/60 (0.00%)  0/60 (0.00%) 
MYALGIA * 1  0/62 (0.00%)  0/63 (0.00%)  0/60 (0.00%)  4/60 (6.67%) 
PAIN IN EXTREMITY * 1  8/62 (12.90%)  8/63 (12.70%)  3/60 (5.00%)  5/60 (8.33%) 
MUSCULOSKELETAL STIFFNESS * 1  0/62 (0.00%)  0/63 (0.00%)  3/60 (5.00%)  1/60 (1.67%) 
Nervous system disorders         
DIZZINESS * 1  8/62 (12.90%)  4/63 (6.35%)  5/60 (8.33%)  2/60 (3.33%) 
HEADACHE * 1  9/62 (14.52%)  6/63 (9.52%)  9/60 (15.00%)  10/60 (16.67%) 
PARAESTHESIA * 1  4/62 (6.45%)  2/63 (3.17%)  0/60 (0.00%)  0/60 (0.00%) 
NEUROPATHY PERIPHERAL * 1  4/62 (6.45%)  3/63 (4.76%)  0/60 (0.00%)  0/60 (0.00%) 
AMNESIA * 1  4/62 (6.45%)  0/63 (0.00%)  0/60 (0.00%)  0/60 (0.00%) 
DISTURBANCE IN ATTENTION * 1  0/62 (0.00%)  0/63 (0.00%)  3/60 (5.00%)  0/60 (0.00%) 
COGNITIVE DISORDER * 1  0/62 (0.00%)  0/63 (0.00%)  3/60 (5.00%)  1/60 (1.67%) 
SOMNOLENCE * 1  0/62 (0.00%)  0/63 (0.00%)  3/60 (5.00%)  0/60 (0.00%) 
Psychiatric disorders         
ANXIETY * 1  7/62 (11.29%)  4/63 (6.35%)  0/60 (0.00%)  0/60 (0.00%) 
INSOMNIA * 1  5/62 (8.06%)  4/63 (6.35%)  5/60 (8.33%)  4/60 (6.67%) 
DEPRESSED MOOD * 1  0/62 (0.00%)  0/63 (0.00%)  4/60 (6.67%)  0/60 (0.00%) 
DEPRESSION * 1  0/62 (0.00%)  0/63 (0.00%)  3/60 (5.00%)  3/60 (5.00%) 
Respiratory, thoracic and mediastinal disorders         
COUGH * 1  9/62 (14.52%)  6/63 (9.52%)  2/60 (3.33%)  4/60 (6.67%) 
DYSPNOEA * 1  9/62 (14.52%)  7/63 (11.11%)  5/60 (8.33%)  5/60 (8.33%) 
OROPHARYNGEAL PAIN * 1  4/62 (6.45%)  2/63 (3.17%)  0/60 (0.00%)  0/60 (0.00%) 
Skin and subcutaneous tissue disorders         
ALOPECIA * 1  8/62 (12.90%)  3/63 (4.76%)  5/60 (8.33%)  2/60 (3.33%) 
RASH * 1  0/62 (0.00%)  0/63 (0.00%)  3/60 (5.00%)  0/60 (0.00%) 
Vascular disorders         
HOT FLUSH * 1  19/62 (30.65%)  14/63 (22.22%)  14/60 (23.33%)  9/60 (15.00%) 
HYPERTENSION * 1  6/62 (9.68%)  4/63 (6.35%)  0/60 (0.00%)  0/60 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.1
2
Term from vocabulary, MedDRA 20.1
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02007512    
Other Study ID Numbers: MDV3100-12
2013-002717-35 ( EudraCT Number )
C3431008 ( Other Identifier: Alias Study Number )
First Submitted: December 3, 2013
First Posted: December 10, 2013
Results First Submitted: September 21, 2017
Results First Posted: February 6, 2018
Last Update Posted: April 26, 2024