Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Other |
European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Core Questionnaire (QLQ-C30) |
|
Month 24 |
|
| Other |
European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer Module (QLQ-BR23) |
|
Month 24 |
|
| Other |
Number of Participants With Positive Androgen Receptor (AR) Expression by Immunohistochemistry (IHC) |
|
Day 1, 29, 57, 113 and 169 |
|
| Other |
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
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. |
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) |
|
| Other |
Number of Participants With Treatment-Emergent Adverse Events of Grade 3 or Higher Severity |
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. |
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) |
|
| Other |
Number of Participants With Clinically Significant Vital Sign Abnormalities |
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. |
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) |
|
| Other |
Number of Participants With Clinically Significant Laboratory Abnormalities |
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. |
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) |
|
| Other |
Progression Free Survival (PFS): By Electronic Data Capture (EDC) |
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 |
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) |
|
| Other |
Progression Free Survival (PFS): Diagnostic Positive (DX+) Population By Electronic Data Capture (EDC) |
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. |
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) |
|
| Primary |
Progression Free Survival (PFS): Intent-to-Treat (ITT) Population By Interactive Web Recognition System (IWRS) |
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. |
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) |
|
| Primary |
Progression Free Survival (PFS): Diagnostic Positive (DX+) Population By Interactive Web Recognition System (IWRS) |
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. |
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) |
|
| Secondary |
Clinical Benefit Rate-24 (CBR-24) |
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. |
From randomization up to 3 years |
|
| Secondary |
Best Objective Response Rate |
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. |
From randomization until CR or PR, whichever occurred first (up to 3 years) |
|
| Secondary |
Duration of Objective Response |
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. |
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) |
|
| Secondary |
Time to Response |
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. |
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) |
|
| Secondary |
Time to Progression |
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. |
From randomization until PD or last tumor assessment without PD before new antitumor treatment initiation, whichever occurred first (up to 3 years) |
|
| Secondary |
Progression Free Survival (PFS) at 6 Months |
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. |
Month 6 |
|
| Secondary |
Concentration Versus Time Summary of Enzalutamide |
Concentration versus time summary was calculated by setting concentration values below limit of quantitation to zero. |
Predose on Day 29, 57 and 113 |
|
| Secondary |
Concentration Versus Time Summary of Exemestane |
Concentration versus time summary was calculated by setting concentration values below limit of quantitation to zero. |
Predose, 1 and 6 hour postdose on Day 29, 57, 113 and 169 |
|
| Secondary |
Concentration Versus Time Summary of N-desmethyl Enzalutamide |
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. |
Predose on Day 29, 57 and 113 |
|
