A Study of Abiraterone Acetate Plus Prednisone With or Without Exemestane in Postmenopausal Women With Estrogen Receptor-Positive (ER+) Metastatic Breast Cancer Progressing After Letrozole or Anastrozole Therapy

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01381874
• Collaborator: (none)
• Enrollment: 297
• Locations: 85
• Arms: 3
• Actual Duration (Months): 83.5
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and efficacy of oral abiraterone acetate plus oral prednisone and oral abiraterone acetate plus oral prednisone plus oral exemestane, each compared with oral exemestane alone, in postmenopausal women with estrogen receptor-positive (ER+) metastatic (spreading) breast cancer that has relapsed after treatment with letrozole or anastrozole.

Condition or Disease	Intervention/Treatment	Phase
Metastatic ER+ Her2- Breast Cancer; Postmenopausal	Drug: Exemestane; Drug: Abiraterone acetate + Prednisone/ Prednisolone + Exemestane; Drug: Abiraterone acetate + Prednisone or Prednisolone	Phase 2

Detailed Description

This is a randomized (study drug assigned by chance), open-label (all participants will know the identity of the assigned study drug) study divided into three phases, screening, treatment, and follow-up. During screening, potential patients will be assessed for study eligibility after providing signed informed consent. The treatment phase will comprise a series of 28-day cycles with continuous study treatment until breast cancer progression, when an end-of-treatment visit will be completed before the follow-up phase begins. The duration of participation in the study for an individual patient may be up to approximately 7 years, including follow-up evaluations. Patients will be evaluated for the safety and effectiveness of study treatments. During the treatment phase, patients will take the following study drugs by mouth once daily: abiraterone acetate, 1 g/day, as four 250-mg tablets, on an empty stomach, and patients must not eat for at least 1 hour after abiraterone acetate; prednisone (prednisolone when prednisone is not available), 5 mg/day; and exemestane, 25 mg/day, as a single tablet. The treatment phase will consist of a series of 28-day cycles with continuous study treatment until breast cancer progression. At the planned interim analysis, the Data Review Committee has recommended that further randomization to the abiraterone acetate alone group be stopped and that the study is to be continued otherwise.

Study Design

• Study Type: Interventional
• Actual Enrollment: 297 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized, Open-Label Study of Abiraterone Acetate (JNJ-212082) Plus Prednisone With or Without Exemestane in Postmenopausal Women With ER+ Metastatic Breast Cancer Progressing After Letrozole or Anastrozole Therapy
• Actual Study Start Date: Aug 24, 2011
• Actual Primary Completion Date: Jul 28, 2014
• Actual Study Completion Date: Aug 8, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abiraterone acetate + Prednisone or Prednisolone Abiraterone acetate + Prednisone or Prednisolone Abiraterone acetate type=equal unit=mg number=250 form=tablet route=oral use 4 tablets Prednisone or Prednisolone type=equal unit=mg number=5 form=tablet route=oral use. All drugs are taken once daily.	Drug: Abiraterone acetate + Prednisone or Prednisolone; Abiraterone acetate, type=equal, unit=mg, number=250, form=tablet, route=oral use, 4 tablets
Experimental: Abiraterone acetate + Prednisone/Prednisolone + Exemestane Abiraterone acetate + Prednisone/Prednisolone + Exemestane Abiraterone acetate type=equal unit=mg number=250 form=tablet route=oral use 4 tablets Prednisone or Prednisolone type=equal unit=mg number=5 form=tablet route=oral use Exemestane type=equal unit=mg number=25 form=tablet route=oral use. All drugs are taken once daily.	Drug: Abiraterone acetate + Prednisone/ Prednisolone + Exemestane; Prednisone or Prednisolone, type=equal, unit=mg, number=5, form=tablet, route=oral use. All drugs are taken once daily.
Experimental: Exemestane Exemestane Exemestane type=equal unit=mg number=25 form=tablet route=oral use. All drugs are taken once daily.	Drug: Exemestane; Abiraterone acetate, type=equal, unit=mg, number=250, form=tablet, route=oral use, 4 tablets

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [Approximately 2 years]

   Progression-free survival was defined as the time from randomization to first occurrence of disease progression (either radiographic or clinical), or death from any cause. PFS was determined using radiographic progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) on measurable lesions captured by computed tomography (CT) or magnetic resonance imaging (MRI). Clinical disease progression was considered only when disease progression could not be confirmed by CT or MRI, such as when the disease site is skin, bone marrow, or central nervous system.

2. Overall Survival (OS) [Approximately 3 years]

   OS was calculated as the time from randomization to death from any cause.

Secondary Outcome Measures

1. Overall Response Rate (ORR) [Approximately 2 years]

   Overall response rate was defined as the percentage of participants with measurable disease achieving a best overall response of either complete response (CR) or partial response (PR) based on RECIST. CR: disappearance of all target lesions and non-target lesions. PR: at least a 30 percent (%) decrease in the sum of longest diameter (LD) of target lesions or persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.

2. Clinical Benefit Rate [Approximately 2 years]

   Clinical benefit rate was defined as the percentage of participants with measurable disease achieving a best overall response of a CR, PR, or stable disease (SD) for at least 6 months based on RECIST. Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.

3. Duration of Response [Approximately 2 years]

   Duration of objective response was measured from the first time that the CR or PR was achieved to the first observation of disease progression (either radiographic or clinical) based on the RECIST criteria.

4. Change From Baseline in Serum Endocrine Biomarkers (Estradiol and Estrone) at End of Treatment [Baseline and End of treatment (approximately 2 years)]

   Change from baseline in serum endocrine biomarkers (estradiol and estrone) was summarized by treatment at end of treatment.

5. Change From Baseline in Serum Endocrine Biomarkers (Progesterone and Testosterone) at End of Treatment [Baseline and End of treatment (approximately 2 years)]

   Change from baseline in serum endocrine biomarkers (Progesterone and Testosterone) was summarized by treatment at end of treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Female patients must be postmenopausal

• ER+, Human epidermal growth factor receptor 2 (Her2) negative metastatic breast cancer

• Disease must have been sensitive to anastrozole or letrozole therapy prior to disease progression

• No more than two prior lines of therapy in the metastatic setting, of which no more than one was chemotherapy

• Eastern Cooperative Oncology Group (ECOG) performance status score of <=1

• Patients with disease confined only to bone may be included, but patients with purely sclerotic lesions may not participate in the study

Exclusion Criteria:

• Prior treatment with exemestane, ketoconazole, aminoglutethimide, or a CYP17 inhibitor. Prior treatment with ketoconazole for <= 7 days is permitted and topical formulations of ketoconazole are permitted

• Potential patients must not have taken anastrozole, letrozole, fulvestrant, or any chemotherapy for at least 2 weeks (bevacizumab for at least 3 weeks) before randomization

• Anticancer immunotherapy or investigational agent within 4 weeks before randomization, or anticancer radiotherapy (except palliative) or anticancer endocrine therapy within 2 weeks before randomization

• Serious or uncontrolled nonmalignant disease, including active or uncontrolled infection

• Clinical or biochemical evidence of hyperaldosteronism or hypopituitarism

• Any condition that, in the opinion of the investigator, would compromise the well-being of the patient or that could prevent, limit, or confound the protocol-specified assessments

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Muscle Shoals	Alabama	United States
2		Fresno	California	United States
3		Los Angeles	California	United States
4		Monterey	California	United States
5		Chicago	Illinois	United States
6		Waterville	Maine	United States
7		Boston	Massachusetts	United States
8		Ann Arbor	Michigan	United States
9		Henderson	Nevada	United States
10		East Syracuse	New York	United States
11		Johnson City	New York	United States
12		New York	New York	United States
13		Durham	North Carolina	United States
14		Fargo	North Dakota	United States
15		Cleveland	Ohio	United States
16		Columbus	Ohio	United States
17		Kettering	Ohio	United States
18		Portland	Oregon	United States
19		Sioux Falls	South Dakota	United States
20		Dallas	Texas	United States
21		El Paso	Texas	United States
22		Houston	Texas	United States
23		Tyler	Texas	United States
24		Seattle	Washington	United States
25		Antwerpen		Belgium
26		Brussels		Belgium
27		Brussel		Belgium
28		Bruxelles		Belgium
29		Duffel		Belgium
30		Edegem		Belgium
31		Gent		Belgium
32		Hasselt		Belgium
33		Leuven		Belgium
34		Liège		Belgium
35		Wilrijk		Belgium
36		Bordeaux		France
37		Caen Cedex 05		France
38		Pierre Benite		France
39		Saint Herblain		France
40		Saint-cloud		France
41		Galway		Ireland
42		Limerick		Ireland
43		Busan		Korea, Republic of
44		Seoul		Korea, Republic of
45		Suwon		Korea, Republic of
46		Luxembourg		Luxembourg
47		Niederkorn		Luxembourg
48		Alkmaar		Netherlands
49		Amsterdam		Netherlands
50		Heerlen		Netherlands
51		Leeuwarden		Netherlands
52		Leiden		Netherlands
53		Rotterdam		Netherlands
54		Sittard		Netherlands
55		Bialystok		Poland
56		Warszawa		Poland
57		Chelyabinsk		Russian Federation
58		Kazan		Russian Federation
59		Leningrad Region		Russian Federation
60		Moscow		Russian Federation
61		Saint-Petersburg,		Russian Federation
62		Sochi		Russian Federation
63		St Petersburg		Russian Federation
64		Stavropol		Russian Federation
65		Vladimir		Russian Federation
66		Barcelona		Spain
67		Madrid N/a		Spain
68		Madrid		Spain
69		Sevilla		Spain
70		Valencia		Spain
71		Chernivtsi		Ukraine
72		Dnepropetrovsk		Ukraine
73		Donetsk		Ukraine
74		Kharkov		Ukraine
75		Odessa		Ukraine
76		Tcherkassy		Ukraine
77		Uzhgorod		Ukraine
78		Bath		United Kingdom
79		Birmingham		United Kingdom
80		Exeter		United Kingdom
81		London		United Kingdom
82		Nottingham		United Kingdom
83		Plymouth		United Kingdom
84		Sheffield		United Kingdom
85		Sutton		United Kingdom

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

• Study Protocol - Apr 27, 2015
• Statistical Analysis Plan - Jul 30, 2013

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT01381874
• Other Study ID Numbers: CR018286; 212082BCA2001; 2011-000621-80; NCT01355770
• First Posted: Jun 27, 2011
• Last Update Posted: Apr 11, 2019
• Last Verified: Mar 1, 2019

• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Janssen Research & Development, LLC: Breast cancer; Abiraterone; Postmenopausal; Metastatic
• Additional relevant MeSH terms: Breast Neoplasms; Prednisone; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Exemestane; Abiraterone Acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Study Results

Participant Flow

Arm/Group Title	Exemestane	Abiraterone Acetate + Prednisone	Abiraterone Acetate + Exemestane + Prednisone
Arm/Group Description	Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Period Title: Overall Study
STARTED	102	89	106
Treated	102	87	104
COMPLETED	25	26	30
NOT COMPLETED	77	63	76

Baseline Characteristics

Arm/Group Title	Exemestane	Abiraterone Acetate + Prednisone	Abiraterone Acetate + Exemestane + Prednisone	Total
Arm/Group Description	Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Total of all reporting groups
Overall Participants	102	89	106	297
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.9 (8.55)	63.1 (9.17)	63.8 (10.91)	62.9 (9.63)
Sex: Female, Male (Count of Participants)
Female	102 100%	89 100%	106 100%	297 100%
Male	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 2.2%	1 0.9%	3 1%
Not Hispanic or Latino	84 82.4%	72 80.9%	95 89.6%	251 84.5%
Unknown or Not Reported	18 17.6%	15 16.9%	10 9.4%	43 14.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 1%	1 1.1%	5 4.7%	7 2.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	92 90.2%	76 85.4%	96 90.6%	264 88.9%
More than one race	0 0%	1 1.1%	1 0.9%	2 0.7%
Unknown or Not Reported	9 8.8%	11 12.4%	4 3.8%	24 8.1%
Region of Enrollment (Count of Participants)
USA	9 8.8%	11 12.4%	8 7.5%	28 9.4%
Belgium	18 17.6%	21 23.6%	21 19.8%	60 20.2%
France	17 16.7%	13 14.6%	11 10.4%	41 13.8%
Spain	11 10.8%	7 7.9%	12 11.3%	30 10.1%
United Kingdom	7 6.9%	12 13.5%	11 10.4%	30 10.1%
Italy	0 0%	1 1.1%	4 3.8%	5 1.7%
Korea, Republic Of	1 1%	0 0%	5 4.7%	6 2%
Netherlands	8 7.8%	5 5.6%	8 7.5%	21 7.1%
Russia	20 19.6%	12 13.5%	19 17.9%	51 17.2%
Ukraine	11 10.8%	7 7.9%	7 6.6%	25 8.4%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	Progression-free survival was defined as the time from randomization to first occurrence of disease progression (either radiographic or clinical), or death from any cause. PFS was determined using radiographic progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) on measurable lesions captured by computed tomography (CT) or magnetic resonance imaging (MRI). Clinical disease progression was considered only when disease progression could not be confirmed by CT or MRI, such as when the disease site is skin, bone marrow, or central nervous system.
Time Frame	Approximately 2 years

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) analysis set included all participants randomized into the study.

Arm/Group Title	Exemestane	Abiraterone Acetate + Prednisone	Abiraterone Acetate + Exemestane + Prednisone
Arm/Group Description	Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Measure Participants	102	89	106
Median (95% Confidence Interval) [Months]	3.68	3.65	4.47

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exemestane, Abiraterone Acetate + Prednisone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.437
	Comments
	Method	stratified log-rank test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.143
	Confidence Interval	(2-Sided) 95%; 0.816 to 1.603
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exemestane, Abiraterone Acetate + Exemestane + Prednisone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.794
	Comments
	Method	stratified log-rank test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.958
	Confidence Interval	(2-Sided) 95%; 0.695 to 1.320
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Overall Survival (OS)
Description	OS was calculated as the time from randomization to death from any cause.
Time Frame	Approximately 3 years

Outcome Measure Data

Analysis Population Description

ITT analysis set included all participants randomized into the study.

Arm/Group Title	Exemestane	Abiraterone Acetate + Prednisone	Abiraterone Acetate + Exemestane + Prednisone
Arm/Group Description	Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Measure Participants	102	89	106
Median (95% Confidence Interval) [Months]	NA	26.41	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exemestane, Abiraterone Acetate + Prednisone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.807
	Comments
	Method	stratified log-rank test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.074
	Confidence Interval	(2-Sided) 95%; 0.608 to 1.896
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exemestane, Abiraterone Acetate + Exemestane + Prednisone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.542
	Comments
	Method	stratified log-rank test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.183
	Confidence Interval	(2-Sided) 95%; 0.688 to 2.036
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	Overall response rate was defined as the percentage of participants with measurable disease achieving a best overall response of either complete response (CR) or partial response (PR) based on RECIST. CR: disappearance of all target lesions and non-target lesions. PR: at least a 30 percent (%) decrease in the sum of longest diameter (LD) of target lesions or persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.
Time Frame	Approximately 2 years

Outcome Measure Data

Analysis Population Description

ITT analysis set with measurable disease at baseline.

Arm/Group Title	Exemestane	Abiraterone Acetate + Prednisone	Abiraterone Acetate + Exemestane + Prednisone
Arm/Group Description	Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Measure Participants	63	52	66
Number [Percentage of participants]	6.3 6.2%	5.8 6.5%	12.1 11.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exemestane, Abiraterone Acetate + Prednisone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.909
	Confidence Interval	(2-Sided) 95%; 0.213 to 3.878
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exemestane, Abiraterone Acetate + Exemestane + Prednisone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.366
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.909
	Confidence Interval	(2-Sided) 95%; 0.605 to 6.026
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Clinical Benefit Rate
Description	Clinical benefit rate was defined as the percentage of participants with measurable disease achieving a best overall response of a CR, PR, or stable disease (SD) for at least 6 months based on RECIST. Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.
Time Frame	Approximately 2 years

Outcome Measure Data

Analysis Population Description

ITT analysis set with measurable disease at baseline.

Arm/Group Title	Exemestane	Abiraterone Acetate + Prednisone	Abiraterone Acetate + Exemestane + Prednisone
Arm/Group Description	Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Measure Participants	63	52	66
Number [Percentage of participants]	12.7 12.5%	9.6 10.8%	22.7 21.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exemestane, Abiraterone Acetate + Prednisone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.603
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.757
	Confidence Interval	(2-Sided) 95%; 0.264 to 2.175
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exemestane, Abiraterone Acetate + Exemestane + Prednisone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.137
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.790
	Confidence Interval	(2-Sided) 95%; 0.816 to 3.926
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Duration of Response
Description	Duration of objective response was measured from the first time that the CR or PR was achieved to the first observation of disease progression (either radiographic or clinical) based on the RECIST criteria.
Time Frame	Approximately 2 years

Outcome Measure Data

Analysis Population Description

ITT analysis set with measurable disease at baseline with complete or partial response.

Arm/Group Title	Exemestane	Abiraterone Acetate + Prednisone	Abiraterone Acetate + Exemestane + Prednisone
Arm/Group Description	Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Measure Participants	4	3	8
Median (95% Confidence Interval) [months]	6.47	4.86	6.93

6. Secondary Outcome

Title	Change From Baseline in Serum Endocrine Biomarkers (Estradiol and Estrone) at End of Treatment
Description	Change from baseline in serum endocrine biomarkers (estradiol and estrone) was summarized by treatment at end of treatment.
Time Frame	Baseline and End of treatment (approximately 2 years)

Outcome Measure Data

Analysis Population Description

ITT analysis set with valid baseline value and at least 1 post baseline value. Here "n" (number analyzed)" signifies participants evaluable for specified categories.

Arm/Group Title	Exemestane	Abiraterone Acetate + Prednisone	Abiraterone Acetate + Exemestane + Prednisone
Arm/Group Description	Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Measure Participants	50	49	56
Estradiol	1.53 (27.643)	-3.35 (13.634)	-1.04 (20.146)
Estrone	-34.20 (83.770)	-28.09 (47.779)	-30.60 (42.385)

7. Secondary Outcome

Title	Change From Baseline in Serum Endocrine Biomarkers (Progesterone and Testosterone) at End of Treatment
Description	Change from baseline in serum endocrine biomarkers (Progesterone and Testosterone) was summarized by treatment at end of treatment.
Time Frame	Baseline and End of treatment (approximately 2 years)

Outcome Measure Data

Analysis Population Description

ITT analysis set with valid baseline value and at least 1 post baseline value. Here "n" (number analyzed)" signifies participants evaluable for specified categories.

Arm/Group Title	Exemestane	Abiraterone Acetate + Prednisone	Abiraterone Acetate + Exemestane + Prednisone
Arm/Group Description	Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).	Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
Measure Participants	53	50	56
Progesterone	-4.80 (18.268)	8.98 (15.113)	12.34 (16.967)
Testosterone	-0.09 (0.416)	-0.51 (0.459)	-0.48 (0.323)

Adverse Events

Time Frame	Approximately 3 years
Adverse Event Reporting Description	Safety population was defined as all randomized participants who received at least one dose of study drug.
Arm/Group Title	Exemestane		Abiraterone Acetate + Prednisone		Abiraterone Acetate + Exemestane + Prednisone
Arm/Group Description	Participants received exemestane tablet as oral dose of 25 milligram (mg) per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).		Participants received abiraterone acetate tablet at a total oral dose of 1000 milligram (mg) along with 5 mg capsule of prednisone/prednisolone per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).		Participants received abiraterone acetate tablet at a total oral dose of 1000 mg and 5 mg capsule of prednisone/prednisolone along with exemestane tablet 25 mg per day in 28-day treatment cycles until disease progression, unacceptable toxicity, or death (up to 3 years).
All Cause Mortality
	Exemestane		Abiraterone Acetate + Prednisone		Abiraterone Acetate + Exemestane + Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/102 (1%)		0/87 (0%)		2/104 (1.9%)
Serious Adverse Events
	Exemestane		Abiraterone Acetate + Prednisone		Abiraterone Acetate + Exemestane + Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/102 (11.8%)		18/87 (20.7%)		28/104 (26.9%)
Blood and lymphatic system disorders
Anaemia	0/102 (0%)		0/87 (0%)		1/104 (1%)
Febrile Neutropenia	0/102 (0%)		0/87 (0%)		1/104 (1%)
Cardiac disorders
Atrial Fibrillation	0/102 (0%)		1/87 (1.1%)		1/104 (1%)
Cardiac Failure Congestive	0/102 (0%)		0/87 (0%)		1/104 (1%)
Ear and labyrinth disorders
Vertigo	1/102 (1%)		0/87 (0%)		0/104 (0%)
Endocrine disorders
Hypoaldosteronism	0/102 (0%)		0/87 (0%)		1/104 (1%)
Gastrointestinal disorders
Abdominal Pain	0/102 (0%)		0/87 (0%)		3/104 (2.9%)
Anorectal Varices	0/102 (0%)		0/87 (0%)		1/104 (1%)
Ascites	0/102 (0%)		0/87 (0%)		1/104 (1%)
Crohn's Disease	0/102 (0%)		1/87 (1.1%)		0/104 (0%)
Faecal Incontinence	0/102 (0%)		1/87 (1.1%)		0/104 (0%)
Small Intestinal Obstruction	0/102 (0%)		1/87 (1.1%)		0/104 (0%)
Volvulus of Small Bowel	1/102 (1%)		0/87 (0%)		0/104 (0%)
Vomiting	0/102 (0%)		0/87 (0%)		3/104 (2.9%)
General disorders
Asthenia	0/102 (0%)		1/87 (1.1%)		1/104 (1%)
Fatigue	0/102 (0%)		0/87 (0%)		1/104 (1%)
Malaise	0/102 (0%)		0/87 (0%)		1/104 (1%)
Non-Cardiac Chest Pain	1/102 (1%)		0/87 (0%)		1/104 (1%)
Hepatobiliary disorders
Hepatitis Toxic	0/102 (0%)		0/87 (0%)		1/104 (1%)
Hyperbilirubinaemia	0/102 (0%)		0/87 (0%)		1/104 (1%)
Infections and infestations
Bronchitis	0/102 (0%)		0/87 (0%)		1/104 (1%)
Bronchopneumonia	0/102 (0%)		0/87 (0%)		1/104 (1%)
Cellulitis	0/102 (0%)		0/87 (0%)		1/104 (1%)
Device Related Infection	0/102 (0%)		0/87 (0%)		1/104 (1%)
Gastroenteritis	0/102 (0%)		0/87 (0%)		1/104 (1%)
Respiratory Tract Infection	1/102 (1%)		0/87 (0%)		0/104 (0%)
Urinary Tract Infection	0/102 (0%)		1/87 (1.1%)		0/104 (0%)
Urosepsis	1/102 (1%)		0/87 (0%)		1/104 (1%)
Injury, poisoning and procedural complications
Compression Fracture	0/102 (0%)		0/87 (0%)		1/104 (1%)
Hip Fracture	0/102 (0%)		1/87 (1.1%)		0/104 (0%)
Lower Limb Fracture	1/102 (1%)		0/87 (0%)		0/104 (0%)
Investigations
Aspartate Aminotransferase Increased	0/102 (0%)		0/87 (0%)		1/104 (1%)
Metabolism and nutrition disorders
Decreased Appetite	0/102 (0%)		0/87 (0%)		1/104 (1%)
Hypokalaemia	1/102 (1%)		3/87 (3.4%)		0/104 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/102 (1%)		0/87 (0%)		0/104 (0%)
Back Pain	0/102 (0%)		2/87 (2.3%)		0/104 (0%)
Bone Pain	0/102 (0%)		1/87 (1.1%)		0/104 (0%)
Flank Pain	0/102 (0%)		0/87 (0%)		1/104 (1%)
Intervertebral Disc Protrusion	0/102 (0%)		2/87 (2.3%)		0/104 (0%)
Mobility Decreased	0/102 (0%)		1/87 (1.1%)		0/104 (0%)
Myalgia	0/102 (0%)		0/87 (0%)		1/104 (1%)
Pain in Extremity	1/102 (1%)		1/87 (1.1%)		0/104 (0%)
Pathological Fracture	0/102 (0%)		2/87 (2.3%)		0/104 (0%)
Synovial Cyst	0/102 (0%)		1/87 (1.1%)		0/104 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to Bone	0/102 (0%)		0/87 (0%)		1/104 (1%)
Metastases to Peripheral Nervous System	0/102 (0%)		0/87 (0%)		1/104 (1%)
Metastases to Pleura	0/102 (0%)		0/87 (0%)		1/104 (1%)
Nervous system disorders
Balance Disorder	1/102 (1%)		0/87 (0%)		0/104 (0%)
Sciatica	1/102 (1%)		0/87 (0%)		0/104 (0%)
Vascular Encephalopathy	0/102 (0%)		0/87 (0%)		1/104 (1%)
Psychiatric disorders
Confusional State	0/102 (0%)		1/87 (1.1%)		0/104 (0%)
Delirium	0/102 (0%)		0/87 (0%)		1/104 (1%)
Renal and urinary disorders
Urinary Retention	0/102 (0%)		0/87 (0%)		1/104 (1%)
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	0/102 (0%)		0/87 (0%)		1/104 (1%)
Dysphonia	0/102 (0%)		1/87 (1.1%)		0/104 (0%)
Dyspnoea	1/102 (1%)		0/87 (0%)		3/104 (2.9%)
Hypoxia	0/102 (0%)		0/87 (0%)		1/104 (1%)
Pleural Effusion	1/102 (1%)		1/87 (1.1%)		2/104 (1.9%)
Pulmonary Toxicity	0/102 (0%)		1/87 (1.1%)		0/104 (0%)
Vascular disorders
Peripheral Artery Stenosis	0/102 (0%)		0/87 (0%)		1/104 (1%)
Thrombosis	0/102 (0%)		0/87 (0%)		1/104 (1%)
Other (Not Including Serious) Adverse Events
	Exemestane		Abiraterone Acetate + Prednisone		Abiraterone Acetate + Exemestane + Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	79/102 (77.5%)		76/87 (87.4%)		84/104 (80.8%)
Blood and lymphatic system disorders
Anaemia	7/102 (6.9%)		6/87 (6.9%)		9/104 (8.7%)
Gastrointestinal disorders
Abdominal Pain	7/102 (6.9%)		4/87 (4.6%)		14/104 (13.5%)
Constipation	9/102 (8.8%)		14/87 (16.1%)		15/104 (14.4%)
Diarrhoea	9/102 (8.8%)		5/87 (5.7%)		13/104 (12.5%)
Dyspepsia	3/102 (2.9%)		5/87 (5.7%)		6/104 (5.8%)
Nausea	18/102 (17.6%)		21/87 (24.1%)		22/104 (21.2%)
Vomiting	7/102 (6.9%)		12/87 (13.8%)		19/104 (18.3%)
General disorders
Asthenia	12/102 (11.8%)		5/87 (5.7%)		9/104 (8.7%)
Fatigue	27/102 (26.5%)		24/87 (27.6%)		21/104 (20.2%)
Influenza Like Illness	7/102 (6.9%)		0/87 (0%)		2/104 (1.9%)
Oedema Peripheral	7/102 (6.9%)		6/87 (6.9%)		10/104 (9.6%)
Infections and infestations
Bronchitis	4/102 (3.9%)		7/87 (8%)		8/104 (7.7%)
Nasopharyngitis	11/102 (10.8%)		5/87 (5.7%)		9/104 (8.7%)
Urinary Tract Infection	0/102 (0%)		6/87 (6.9%)		6/104 (5.8%)
Investigations
Alanine Aminotransferase Increased	7/102 (6.9%)		5/87 (5.7%)		11/104 (10.6%)
Aspartate Aminotransferase Increased	8/102 (7.8%)		5/87 (5.7%)		14/104 (13.5%)
Weight Decreased	4/102 (3.9%)		1/87 (1.1%)		8/104 (7.7%)
Metabolism and nutrition disorders
Decreased Appetite	11/102 (10.8%)		13/87 (14.9%)		17/104 (16.3%)
Hypercholesterolaemia	1/102 (1%)		0/87 (0%)		6/104 (5.8%)
Hyperglycaemia	6/102 (5.9%)		3/87 (3.4%)		7/104 (6.7%)
Hypokalaemia	4/102 (3.9%)		19/87 (21.8%)		14/104 (13.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	17/102 (16.7%)		8/87 (9.2%)		11/104 (10.6%)
Back Pain	12/102 (11.8%)		15/87 (17.2%)		17/104 (16.3%)
Bone Pain	18/102 (17.6%)		13/87 (14.9%)		13/104 (12.5%)
Muscle Spasms	2/102 (2%)		5/87 (5.7%)		7/104 (6.7%)
Musculoskeletal Pain	6/102 (5.9%)		7/87 (8%)		9/104 (8.7%)
Myalgia	11/102 (10.8%)		4/87 (4.6%)		5/104 (4.8%)
Pain in Extremity	7/102 (6.9%)		7/87 (8%)		10/104 (9.6%)
Nervous system disorders
Dizziness	7/102 (6.9%)		4/87 (4.6%)		8/104 (7.7%)
Dysgeusia	2/102 (2%)		5/87 (5.7%)		1/104 (1%)
Headache	10/102 (9.8%)		6/87 (6.9%)		15/104 (14.4%)
Psychiatric disorders
Insomnia	9/102 (8.8%)		4/87 (4.6%)		5/104 (4.8%)
Respiratory, thoracic and mediastinal disorders
Cough	4/102 (3.9%)		9/87 (10.3%)		12/104 (11.5%)
Dyspnoea	8/102 (7.8%)		6/87 (6.9%)		14/104 (13.5%)
Oropharyngeal Pain	0/102 (0%)		6/87 (6.9%)		3/104 (2.9%)
Skin and subcutaneous tissue disorders
Pruritus	2/102 (2%)		1/87 (1.1%)		6/104 (5.8%)
Vascular disorders
Hot Flush	14/102 (13.7%)		14/87 (16.1%)		9/104 (8.7%)
Hypertension	10/102 (9.8%)		7/87 (8%)		15/104 (14.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.