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

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.

Time frame: 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.

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.

Time frame: 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.

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.

Time frame: 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)

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. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

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.

Time frame: 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.

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.

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

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. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

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.

Time frame: 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.

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.

Time frame: Week 24

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.

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.

Time frame: 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.

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.

Time frame: 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.

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.

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

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. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

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.

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

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. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

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.

Time frame: 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.

Time frame: 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.

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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline up to 87 weeks

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

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

Time frame: 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.