Trial Outcomes & Findings for Safety and Efficacy Study of Enzalutamide in Patients With Advanced, Androgen Receptor-Positive, Triple Negative Breast Cancer (NCT NCT01889238)

Last Updated: 2024-12-13

Results Overview

Percentage of participants with a clinical benefit at Week 16 defined as percentage of participants with a best response of complete response (CR), partial response(PR), stable disease(SD) for \>=16 weeks on radiologic imaging based on Investigator assessment using Response Evaluation Criteria in Solid Tumors version 1.1(RECIST 1.1). An estimate of the percentage and its exact 2-sided 85% confidence interval(CI) were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size \<10mm short axis. PR: At least 30% decrease in sum of longest diameter (LD) of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

118 participants

Primary outcome timeframe

Week 16

Results posted on

2024-12-13

Participant Flow

Total of 118 participants with advanced androgen receptor positive (AR+) and triple-negative breast cancer (TNBC) were enrolled at total of 34 study sites in North America and Europe to attain total of 78 evaluable participants.

Participant milestones

Participant milestones
Measure	Enzalutamide Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Overall Study STARTED	118
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	118

Reasons for withdrawal

Reasons for withdrawal
Measure	Enzalutamide Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Overall Study Death	1
Overall Study Withdrawal by Subject	1
Overall Study Adverse Event	6
Overall Study Disease Progression	104
Overall Study Other	6

Baseline Characteristics

Safety and Efficacy Study of Enzalutamide in Patients With Advanced, Androgen Receptor-Positive, Triple Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Enzalutamide n=118 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Age, Continuous	58.3 years STANDARD_DEVIATION 12.95 • n=93 Participants
Sex: Female, Male Female	118 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	108 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=93 Participants
Race (NIH/OMB) Asian	6 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	20 Participants n=93 Participants
Race (NIH/OMB) White	91 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants

PRIMARY outcome

Timeframe: Week 16

Population: Evaluable population included all enrolled participants who had centrally assessed AR + breast cancer (total nuclear AR expression in \>= 10% of tumor cells), had at least 1 dose of study drug and had at least 1 available post baseline tumor assessment evaluable as per RECIST 1.1.

Outcome measures

Outcome measures
Measure	Enzalutamide n=78 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Percentage of Participants With Clinical Benefit at Week 16: Evaluable Population	33.3 Percentage of participants Interval 25.53 to 41.63

PRIMARY outcome

Timeframe: Week 16

Population: ITT population included all enrolled participants who had centrally assessed AR+ breast cancer and received at least 1 dose of study drug.

Percentage of participants with a clinical benefit at Week 16 defined as percentage of participants with a best response of CR, PR, or SD for \>= 16 weeks on radiologic imaging based on Investigator assessment using RECIST 1.1. An estimate of the percentage and its exact 2-sided 85% CI were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size \<10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference.

Outcome measures

Outcome measures
Measure	Enzalutamide n=118 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Percentage of Participants With Clinical Benefit at Week 16: Intent-to-Treat (ITT) Population	24.6 Percentage of participants Interval 18.98 to 30.88

SECONDARY outcome

Timeframe: Week 24

Percentage of participants with a clinical benefit at Week 24 defined as percentage of participants with a best response of CR, PR, or SD for \>= 24 weeks on radiologic imaging based on investigator assessment using RECIST 1.1. An estimate of the percentage and its exact 2-sided 85% CI were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size \<10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference.

Outcome measures

Outcome measures
Measure	Enzalutamide n=78 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Percentage of Participants With Clinical Benefit at Week 24: Evaluable Population	28.2 Percentage of participants Interval 21.04 to 36.48

SECONDARY outcome

Timeframe: Week 24

Population: ITT population included all enrolled participants who had centrally assessed AR+ breast cancer and received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Enzalutamide n=118 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Percentage of Participants With Clinical Benefit at Week 24: ITT Population	20.3 Percentage of participants Interval 15.16 to 26.21

SECONDARY outcome

Timeframe: From Baseline up to disease progression or death due to any cause (up to 87 Weeks)

Percentage of participants with best objective response defined as percentage of participants with a best response of CR and PR based on investigator assessment of target, non-target and new lesions using RECIST 1.1. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in \<10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions.

Outcome measures

Outcome measures
Measure	Enzalutamide n=59 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Percentage of Participants With Best Objective Response: Evaluable Population	8.5 Percentage of participants Interval 3.05 to 12.02

SECONDARY outcome

Timeframe: From Baseline up to disease progression or death due to any cause (up to 87 Weeks)

Population: ITT population included all enrolled participants who had centrally assessed AR+ breast cancer and received at least 1 dose of study drug. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Enzalutamide n=97 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Percentage of Participants With Best Objective Response: ITT Population	6.2 Percentage of participants Interval 2.8 to 8.95

SECONDARY outcome

Timeframe: From Baseline up to disease progression or death due to any cause (up to 87 Weeks)

PFS was defined as the time (in weeks) from the date of first dose of study drug to the date of documented disease progression or death due to any cause whichever occurs first as determined by the investigator using RECIST 1.1. As per RECIST 1.1, progression was defined as: \>=20 percent increase in sum of LD of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions.

Outcome measures

Outcome measures
Measure	Enzalutamide n=78 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Progression-Free Survival (PFS): Evaluable Population	14.3 Weeks Interval 8.3 to 16.1

SECONDARY outcome

Timeframe: From Baseline up to disease progression or death due to any cause (up to 87 Weeks)

Population: ITT population included all enrolled participants who had centrally assessed AR+ breast cancer and received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Enzalutamide n=118 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Progression-Free Survival: ITT Population	12.6 Weeks Interval 8.1 to 15.1

SECONDARY outcome

Timeframe: From first dose of study drug until first documentation of CR or PR or data censoring date, whichever occurred first (up to 87 Weeks)

The time to response is defined as the time from the date of first dose of study drug to initial CR or PR. Participants without response of CR or PR before the data cutoff date were censored at the last tumor assessment date before the data cutoff. Kaplan-Meier method was used to summarize time to response.

Outcome measures

Outcome measures
Measure	Enzalutamide n=59 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Time to Response: Evaluable Population	NA Weeks Median and 95%CI could not be estimated due to insufficient number of participants with the event.

SECONDARY outcome

Timeframe: From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (up to 87 Weeks)

Duration of objective response is defined as the time from initial CR or PR to documented disease progression or death due to any cause, whichever occurs first. Participants without disease progression or death due to any cause before the data cutoff date were censored at the last tumor assessment date before the data cutoff.

Outcome measures

Outcome measures
Measure	Enzalutamide n=59 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Duration of Response: Evaluable Population	NA Weeks Median and 95%CI could not be estimated due to insufficient number of participants with the event.

SECONDARY outcome

Timeframe: From start of study treatment on Day 1 up to 30 days after the last dose of study drug (up to maximum of 9.6 years)

Population: Safety population included all participants who received 1 dose or partial dose of study drug.

Laboratory parameters included hematology parameters \[low lymphocytes (10\^6/L), neutrophils (10\^6/L) and Leukocytes (10\^9/L)\] and chemistry parameters \[high phosphate (mmol/L), bilirubin, Alkaline phosphatase (U/L) and glucose (mmol/L)\]. Number of participants with postbaseline laboratory toxicity Grade 3 or 4 as per NCI-CTCAE (version 4.0) (Grade 3= Severe, Grade 4= Life-threatening) were reported.

Outcome measures

Outcome measures
Measure	Enzalutamide n=118 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Number of Participants With Postbaseline Laboratory Toxicities Grade 3 or 4 Hematology: Leukocytes	1 Participants
Number of Participants With Postbaseline Laboratory Toxicities Grade 3 or 4 Hematology: Lymphocytes	9 Participants
Number of Participants With Postbaseline Laboratory Toxicities Grade 3 or 4 Hematology: Neutrophils	1 Participants
Number of Participants With Postbaseline Laboratory Toxicities Grade 3 or 4 Chemistry: Alkaline Phosphatase	1 Participants
Number of Participants With Postbaseline Laboratory Toxicities Grade 3 or 4 Chemistry: Bilirubin	1 Participants
Number of Participants With Postbaseline Laboratory Toxicities Grade 3 or 4 Chemistry: Glucose	4 Participants
Number of Participants With Postbaseline Laboratory Toxicities Grade 3 or 4 Chemistry: Phosphate	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Predose on Day 1 (Baseline), Week 9 and Week 17

Population: Pharmacokinetics (PK) analysis population included all participants who received 1 dose or partial dose of study drug, and who had at least 1 enzalutamide or M2 plasma concentration assessment. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

M2 was the metabolite of enzalutamide. The lower limit of quantitation (LLQ) was 0.0200 micrograms per milliliter (mcg/mL) for enzalutamide and M2.

Outcome measures

Outcome measures
Measure	Enzalutamide n=115 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Trough Plasma Concentration of Enzalutamide and Its Metabolite Enzalutamide: Week 9	12.59 mcg/mL Geometric Coefficient of Variation 33.46
Trough Plasma Concentration of Enzalutamide and Its Metabolite Enzalutamide: Day 1	NA mcg/mL Geometric Coefficient of Variation NA None of the participants had data above LLQ and as per the predefined protocol, values below the limit of quantitation (BLQ) were set to missing and hence not reported.
Trough Plasma Concentration of Enzalutamide and Its Metabolite M2: Day 1	NA mcg/mL Geometric Coefficient of Variation NA None of the participants had data above LLQ and as per the predefined protocol, values below the limit of quantitation (BLQ) were set to missing and hence not reported.
Trough Plasma Concentration of Enzalutamide and Its Metabolite M2: Week 9	13.48 mcg/mL Geometric Coefficient of Variation 35.64
Trough Plasma Concentration of Enzalutamide and Its Metabolite Enzalutamide: Week 17	12.79 mcg/mL Geometric Coefficient of Variation 37.33
Trough Plasma Concentration of Enzalutamide and Its Metabolite M2: Week 17	13.88 mcg/mL Geometric Coefficient of Variation 25.47

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 87 weeks

Population: Safety population included all participants who received 1 dose or partial dose of study drug.

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. Treatment emergent are events that were absent before treatment or that worsened relative to pretreatment state between first dose of study drug and up to 30 days after last dose of study drug or the day prior to initiation of new anti-tumor treatment. AEs included both serious and non-serious AEs.

Outcome measures

Outcome measures
Measure	Enzalutamide n=118 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Treatment emergent adverse events	109 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Treatment emergent serious adverse events	29 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 87 weeks

Population: Safety population included all participants who received 1 dose or partial dose of study drug.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Data reported here is for study drug discontinuation due to adverse events.

Outcome measures

Outcome measures
Measure	Enzalutamide n=118 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Number of Participants With Study Drug Discontinuation Due to Adverse Events	8 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 87 weeks

Population: Safety population included all participants who received 1 dose or partial dose of study drug.

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. As per the NCI CTCAE, version 4.0, Grade 3= severe, Grade 4= life-threatening and Grade 5= death. Only the participants with treatment-emergent AEs of Grade 3 (severe) or higher grade were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Enzalutamide n=118 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Number of Participants With Grade 3 or Higher Adverse Events	36 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From start of study treatment on Day 1 up to 30 days after the last dose of study drug (up to maximum of 9.6 years)

Population: Safety population included all participants who received 1 dose or partial dose of study drug.

Criteria: Systolic blood pressure (SBP):absolute SBP\<90 millimeters of mercury (mmHg) and decrease from baseline (DFB)\>30mmHg, absolute SBP\>180mmHg and increase from baseline (IFB)\>40 mmHg, final visit (FV) or 2 consecutive visits (CV) SBP\>=20 mmHg change from baseline (CFB), most extreme post-baseline SBP\>=140mmHg, most extreme post- baseline SBP\>=180mmHg, most extreme SBP\>=140mmHg and\>=20 mmHg CFB, most extreme SBP\>=180mmHg and\>=20mmHg CFB; diastolic blood pressure (DBP): absolute DBP\>105mmHg and IFB\>30mmHg, absolute DBP\<50mmHg and DFB\>20mmHg, final visit or 2 consecutive visits DBP\>=15mmHg CFB, most extreme post-baseline DBP\>=90mmHg, most extreme post-baseline DBP\>=105mmHg, most extreme DBP\>=90mmHg and\>=15mmHg CFB, most extreme DBP\>=105mmHg and\>=15mmHg CFB; heart rate\<50beats per minute (BPM) and DFB\>20BPM or heart rate\>120BPM and IFB\>30BPM. Only those categories, in which at least 1 participant had data were reported.

Outcome measures

Outcome measures
Measure	Enzalutamide n=118 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs SBP:Most extreme SBP>=140 mmHg and>=20 mmHg CFB	12 Participants
Number of Participants With Clinically Significant Change From Baseline in Vital Signs SBP: absolute SBP <90 mmHg and DFB>30 mmHg	1 Participants
Number of Participants With Clinically Significant Change From Baseline in Vital Signs SBP: Most extreme post baseline SBP >=140 mmHg	42 Participants
Number of Participants With Clinically Significant Change From Baseline in Vital Signs SBP: Most extreme post baseline SBP >=180 mmHg	1 Participants
Number of Participants With Clinically Significant Change From Baseline in Vital Signs DBP:Most extreme DBP>=90 mmHg and>=15 mmHg CFB	12 Participants
Number of Participants With Clinically Significant Change From Baseline in Vital Signs DBP:Most extreme DBP>=105 mmHg and>=15 mmHg CFB	2 Participants
Number of Participants With Clinically Significant Change From Baseline in Vital Signs DBP: Most extreme post baseline result >=90 mmHg	24 Participants
Number of Participants With Clinically Significant Change From Baseline in Vital Signs DBP: Most extreme post baseline result >=105 mmHg	4 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From start of study treatment on Day 1 up to 30 days after the last dose of study drug (up to maximum of 9.6 years)

Population: Safety population included all participants who received 1 dose or partial dose of study drug.

Laboratory tests included hematology parameters \[low lymphocytes (10\^6/L), white blood cells (10\^9/L), neutrophils (10\^6/L), hemoglobin gram per Liter(g/L) and platelets (10\^9/L)\] and chemistry parameters \[mean albumin grams per Liter(g/L), calcium milli mole per Liter(mmol/L), Phosphate (mmol/L), alanine aminotransferase units per Liter(U/L), Aspartate aminotransferase (U/L), bilirubin micro mole per Liter, Alkaline phosphatase (U/L) and glucose (mmol/L)\]. Number of participants with change from baseline in laboratory parameters Grades by 2 or More Grades as per NCI-CTCAE (version 4.0) (Grade 2=Moderate, Grade 3= Severe, Grade 4= Life-threatening) were reported.

Outcome measures

Outcome measures
Measure	Enzalutamide n=118 Participants Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades Hematology: Hemoglobin	1 Participants
Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades Hematology: Leukocytes	4 Participants
Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades Hematology: Lymphocytes	12 Participants
Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades Hematology: Neutrophils	2 Participants
Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades Hematology: Platelets	1 Participants
Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades Chemistry: Alanine aminotransferase	1 Participants
Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades Chemistry: Albumin	4 Participants
Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades Chemistry: Alkaline phosphatase	5 Participants
Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades Chemistry: Bilirubin	2 Participants
Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades Chemistry: Calcium	2 Participants
Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades Chemistry: Glucose	5 Participants
Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades Chemistry: Phosphate	4 Participants
Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades Chemistry: Aspartate Aminotransferase	1 Participants

Adverse Events

Enzalutamide

Serious events: 29 serious events

Other events: 106 other events

Deaths: 88 deaths

Serious adverse events

Serious adverse events
Measure	Enzalutamide n=118 participants at risk Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Cardiac disorders Pericardial effusion	1.7% 2/118 • Baseline up to 87 weeks 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.
Cardiac disorders Myocardial infarction	0.85% 1/118 • Baseline up to 87 weeks 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.
Gastrointestinal disorders Constipation	1.7% 2/118 • Baseline up to 87 weeks 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.
Gastrointestinal disorders Nausea	0.85% 1/118 • Baseline up to 87 weeks 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.
General disorders Disease progression	2.5% 3/118 • Baseline up to 87 weeks 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.
General disorders General physical health deterioration	0.85% 1/118 • Baseline up to 87 weeks 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.
General disorders Pain	0.85% 1/118 • Baseline up to 87 weeks 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.
Hepatobiliary disorders Bile duct obstruction	0.85% 1/118 • Baseline up to 87 weeks 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.
Infections and infestations Lung infection	1.7% 2/118 • Baseline up to 87 weeks 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.
Infections and infestations Sepsis	1.7% 2/118 • Baseline up to 87 weeks 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.
Infections and infestations Cellulitis	0.85% 1/118 • Baseline up to 87 weeks 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.
Infections and infestations Device related infection	0.85% 1/118 • Baseline up to 87 weeks 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.
Infections and infestations Respiratory tract infection	0.85% 1/118 • Baseline up to 87 weeks 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.
Infections and infestations Soft tissue infection	0.85% 1/118 • Baseline up to 87 weeks 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.
Injury, poisoning and procedural complications Hip fracture	0.85% 1/118 • Baseline up to 87 weeks 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.
Injury, poisoning and procedural complications Radiation oesophagitis	0.85% 1/118 • Baseline up to 87 weeks 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.
Injury, poisoning and procedural complications Spinal compression fracture	0.85% 1/118 • Baseline up to 87 weeks 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.
Injury, poisoning and procedural complications Toxicity to various agents	0.85% 1/118 • Baseline up to 87 weeks 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.
Injury, poisoning and procedural complications Traumatic fracture	0.85% 1/118 • Baseline up to 87 weeks 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.
Metabolism and nutrition disorders Dehydration	0.85% 1/118 • Baseline up to 87 weeks 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.
Metabolism and nutrition disorders Hypercalcaemia	0.85% 1/118 • Baseline up to 87 weeks 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.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.85% 1/118 • Baseline up to 87 weeks 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.
Musculoskeletal and connective tissue disorders Pathological fracture	0.85% 1/118 • Baseline up to 87 weeks 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	2.5% 3/118 • Baseline up to 87 weeks 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic pain	2.5% 3/118 • Baseline up to 87 weeks 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	1.7% 2/118 • Baseline up to 87 weeks 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pericardial effusion malignant	0.85% 1/118 • Baseline up to 87 weeks 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.85% 1/118 • Baseline up to 87 weeks 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.85% 1/118 • Baseline up to 87 weeks 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.85% 1/118 • Baseline up to 87 weeks 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	0.85% 1/118 • Baseline up to 87 weeks 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.
Nervous system disorders Spinal cord compression	1.7% 2/118 • Baseline up to 87 weeks 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.
Nervous system disorders Cognitive disorder	0.85% 1/118 • Baseline up to 87 weeks 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.
Renal and urinary disorders Renal failure acute	0.85% 1/118 • Baseline up to 87 weeks 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.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.5% 3/118 • Baseline up to 87 weeks 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.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.85% 1/118 • Baseline up to 87 weeks 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.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.85% 1/118 • Baseline up to 87 weeks 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.

Other adverse events

Other adverse events
Measure	Enzalutamide n=118 participants at risk Participants received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), non-compliance with protocol requirements, initiation of a new anti-tumor treatment, or participant or physician decision to discontinue treatment or death due to any cause.
Gastrointestinal disorders Nausea	33.9% 40/118 • Baseline up to 87 weeks 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.
General disorders Fatigue	41.5% 49/118 • Baseline up to 87 weeks 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.
Gastrointestinal disorders Diarrhoea	15.3% 18/118 • Baseline up to 87 weeks 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.
Gastrointestinal disorders Constipation	14.4% 17/118 • Baseline up to 87 weeks 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.
Gastrointestinal disorders Vomiting	9.3% 11/118 • Baseline up to 87 weeks 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.
Gastrointestinal disorders Abdominal pain	5.9% 7/118 • Baseline up to 87 weeks 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.
General disorders Pain	7.6% 9/118 • Baseline up to 87 weeks 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.
General disorders Asthenia	5.1% 6/118 • Baseline up to 87 weeks 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.
Infections and infestations Nasopharyngitis	5.1% 6/118 • Baseline up to 87 weeks 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.
Investigations Weight decreased	6.8% 8/118 • Baseline up to 87 weeks 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.
Metabolism and nutrition disorders Decreased appetite	18.6% 22/118 • Baseline up to 87 weeks 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.
Musculoskeletal and connective tissue disorders Back pain	14.4% 17/118 • Baseline up to 87 weeks 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.
Musculoskeletal and connective tissue disorders Arthralgia	15.3% 18/118 • Baseline up to 87 weeks 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.
Musculoskeletal and connective tissue disorders Pain in extremity	8.5% 10/118 • Baseline up to 87 weeks 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.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.6% 9/118 • Baseline up to 87 weeks 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.
Musculoskeletal and connective tissue disorders Muscle spasms	5.1% 6/118 • Baseline up to 87 weeks 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.
Nervous system disorders Headache	14.4% 17/118 • Baseline up to 87 weeks 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.
Nervous system disorders Dizziness	5.1% 6/118 • Baseline up to 87 weeks 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.
Nervous system disorders Neuropathy peripheral	5.1% 6/118 • Baseline up to 87 weeks 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.
Psychiatric disorders Insomnia	14.4% 17/118 • Baseline up to 87 weeks 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.
Psychiatric disorders Anxiety	5.9% 7/118 • Baseline up to 87 weeks 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.
Reproductive system and breast disorders Breast pain	5.1% 6/118 • Baseline up to 87 weeks 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.0% 13/118 • Baseline up to 87 weeks 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.
Respiratory, thoracic and mediastinal disorders Cough	6.8% 8/118 • Baseline up to 87 weeks 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.
Vascular disorders Hot flush	10.2% 12/118 • Baseline up to 87 weeks 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.
Infections and infestations Upper respiratory tract infection	5.1% 6/118 • Baseline up to 87 weeks 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.
Musculoskeletal and connective tissue disorders Myalgia	5.1% 6/118 • Baseline up to 87 weeks 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.

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER