Trial Outcomes & Findings for A Randomized Study of Enzalutamide in Patients With Localized Prostate Cancer Undergoing Active Surveillance (NCT NCT02799745)

Last Updated: 2024-12-06

Results Overview

Time to cancer prostate progression (pathological or therapeutic): time (in months) from date of randomization until the date of cancer progression (pathological or therapeutic). Pathological progression: increase in primary or secondary Gleason pattern by greater than or equal (\>=) 1 or higher proportion of cancer positive cores (\>=15 percent \[%\] increase). Therapeutic progression: earliest occurrence of primary therapy for prostate cancer (prostatectomy/radiation/focal therapy/systemic therapy). Medians and 95% CIs were calculated with the Kaplan-Meier (KM) method. Participants with no cancer progression at the time of study completion, discontinuation or death were censored at the last assessment date. Participants switching therapy during the study were censored at the time of the initial therapy switch, and participants discontinuing therapy were censored at the time of study discontinuation.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

227 participants

Primary outcome timeframe

From the date of randomization until the date of the cancer progression (pathological or therapeutic) (up to study completion date, 28 Aug 2020; approximately 50 months)

Results posted on

2024-12-06

Participant Flow

Adult participants with clinically localized, histologically proven prostate cancer diagnosed within 6 months of screening and had been on active surveillance were enrolled in this study. Participants were categorized as low risk or intermediate risk and had a minimum of 10 cores from transrectal ultrasound-guided prostate biopsy (multiparametric magnetic resonance imaging \[mpMRI\]-targeted versus non-mpMRI-targeted) done within 6 months prior to screening visit.

Randomization was stratified according to prostate cancer risk (low and intermediate) and type of biopsy performed (mpMRI-targeted and non-mpMRI-targeted). Out of 310 participants who were screened, 83 participants were considered screen failures.

Participant milestones

Participant milestones
Measure	Enzalutamide The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-miligram (mg) enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued active surveillance (AS) for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Overall Study STARTED	114	113
Overall Study Treated	112	113
Overall Study COMPLETED	58	42
Overall Study NOT COMPLETED	56	71

Reasons for withdrawal

Reasons for withdrawal
Measure	Enzalutamide The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-miligram (mg) enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued active surveillance (AS) for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Overall Study Participant moved out of state	1	0
Overall Study Discontinued due to planned surgery	1	0
Overall Study Withdrawal by Subject	16	25
Overall Study Protocol Deviation	4	5
Overall Study Progressive Disease	28	38
Overall Study Lost to Follow-up	3	2
Overall Study Death	3	0
Overall Study Adverse Event	0	1

Baseline Characteristics

A Randomized Study of Enzalutamide in Patients With Localized Prostate Cancer Undergoing Active Surveillance

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Enzalutamide n=114 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Total n=227 Participants Total of all reporting groups
Age, Continuous	65.2 Years STANDARD_DEVIATION 8.18 • n=5 Participants	66.9 Years STANDARD_DEVIATION 7.27 • n=7 Participants	66.1 Years STANDARD_DEVIATION 7.77 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	114 Participants n=5 Participants	113 Participants n=7 Participants	227 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	108 Participants n=5 Participants	107 Participants n=7 Participants	215 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	13 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) White	105 Participants n=5 Participants	99 Participants n=7 Participants	204 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Type of Biopsy mpMRI-targeted	27 Participants n=5 Participants	28 Participants n=7 Participants	55 Participants n=5 Participants
Type of Biopsy non-mpMRI-targeted	87 Participants n=5 Participants	85 Participants n=7 Participants	172 Participants n=5 Participants
Prostate Cancer Risk Low	61 Participants n=5 Participants	60 Participants n=7 Participants	121 Participants n=5 Participants
Prostate Cancer Risk Intermediate	53 Participants n=5 Participants	53 Participants n=7 Participants	106 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of randomization until the date of the cancer progression (pathological or therapeutic) (up to study completion date, 28 Aug 2020; approximately 50 months)

Population: FAS population

Outcome measures

Outcome measures
Measure	Enzalutamide n=114 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Time to Prostate Cancer Progression	NA Months Interval 36.14 to Median and upper limit were not achieved due to low number of events.	NA Months Interval 24.67 to Median and upper limit were not achieved due to low number of events.

SECONDARY outcome

Timeframe: From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020; approximately 50 months)

Population: The safety analysis set (SAF) consisted of all participants who enrolled in the study and were randomized to receive study drug.

An AE: any untoward medical occurrence in a participant administered study drug or who underwent study procedures and did not necessarily had a causal relationship with treatment. An abnormality identified during a medical test: an AE only if the abnormality induced clinical signs or symptoms, required active intervention, required interruption, or discontinuation of study medication, or was clinically significant in the opinion of investigator. An AE: serious if it resulted in any of the following outcomes: Death, was life-threatening, Persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, Congenital anomaly, or birth defect, Inpatient hospitalization or prolongation of hospitalization, Other medically important event. Drug-related AEs: assessed by investigator as AEs whose relationship to study drugs could not be ruled out.

Outcome measures

Outcome measures
Measure	Enzalutamide n=112 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Number of Participants With Adverse Events (AEs) Serious Adverse Events (SAEs)	19 Participants	10 Participants
Number of Participants With Adverse Events (AEs) non-SAEs	103 Participants	67 Participants

SECONDARY outcome

Timeframe: At the end of months 12 and 24

Population: FAS population with available data at each time point.

Percentage of Participants who reported negative biopsies for cancer were reported.

Outcome measures

Outcome measures
Measure	Enzalutamide n=114 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Percentage of Participants Reported Negative Biopsies for Cancer At the end of month 12	35.1 Percentage of participants	14.2 Percentage of participants
Percentage of Participants Reported Negative Biopsies for Cancer At the end of month 24	19.0 Percentage of participants	12.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, months 12 and 24

Population: FAS population with available data at each time point.

Percent positive cores were calculated using the number of systemically sampled prostate regions and any targeted regions with at least 1 positive core divided by the total number of systematically sampled regions and targeted regions. This implied that despite the number of samples within a given systematic or targeted region, any positive core indicated that region as positive.

Outcome measures

Outcome measures
Measure	Enzalutamide n=114 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Change From Baseline in Percent of Cancer Positive Cores at Month 12 and 24 Change at month 12	-14.2 Percent of Cancer positive cores Standard Deviation 15.68	-1.9 Percent of Cancer positive cores Standard Deviation 14.70
Change From Baseline in Percent of Cancer Positive Cores at Month 12 and 24 Change at month 24	-7.3 Percent of Cancer positive cores Standard Deviation 17.74	-0.8 Percent of Cancer positive cores Standard Deviation 21.62

SECONDARY outcome

Timeframe: From date of randomization or first dose of enzalutamide until date of PSA progression (pathological or therapeutic) (up to study completion date=28 Aug 2020, median duration: 14.82 months for "Enzalutamide", 8.80 months for "Active Surveillance")

Population: FAS population

Time to PSA progression was defined as time in months from the date of randomization or first dose enzalutamide untill date of PSA progression (secondary rise in serum PSA \>=25% above baseline or \>=25% above nadir or absolute increase \>= 2 nanogram per mililiter \[ng/mL\]). Participants with no PSA progression at the time of trial completion, discontinuation or death were censored at the last assessment date. Additionally, participants switching therapy during the study were censored at the time of the initial therapy switch, and participants discontinuing therapy were censored at the time of study discontinuation. Medians and 95% CIs were calculated with the KM method.

Outcome measures

Outcome measures
Measure	Enzalutamide n=114 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Time to Prostate-specific Antigen (PSA) Progression	14.82 Months Interval 14.75 to 14.95	8.80 Months Interval 6.05 to 11.53

SECONDARY outcome

Timeframe: At the end of months 12, 24 and at the end of study (up to study completion date, 28 Aug 2020, approximately 50 months)

Population: FAS population with available data at each time point.

Percentage of participants with secondary rise in serum PSA \> 25% baseline or \> 25% above nadir or absolute increase \>2 ng/mL were reported in this measure.

Outcome measures

Outcome measures
Measure	Enzalutamide n=114 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Percentage of Participants With Secondary Rise in Serum PSA At the end of month 12	24.6 Percentage of participants	69.0 Percentage of participants
Percentage of Participants With Secondary Rise in Serum PSA At the end of month 24	92.0 Percentage of participants	92.8 Percentage of participants
Percentage of Participants With Secondary Rise in Serum PSA At the end of study	100.0 Percentage of participants	96.2 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, months 3, 6, 12, 18 and 24

Population: FAS population with available data at each time point.

The BFI is a screening tool designed to assess the severity and impact of fatigue on daily functioning of participants with cancer during the 24 hours. There are 9 items on the scale. The first three questions ask participants to rate their fatigues on a scale from 0 (no fatigue) - 10 (as bad as you can imagine), with higher scores indicating worse outcome. The remaining six questions ask participants to rate how much fatigue has interfered with their daily activities on a scale from 0 (Does not interfere) to 10 (Completely interferes). A composite fatigue score was obtained by averaging all the items on the BFI, ranged between 0 to 10, with a higher BFI fatigue score indicating worse outcome. The composite BFI score was calculated only if at least 5 of the 9 items were answered.

Outcome measures

Outcome measures
Measure	Enzalutamide n=114 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Change From Baseline in Brief Fatigue Inventory (BFI) Questionnaire Composite Scores to Months 3, 6, 12, 18 and 24 Change at month 3	0.7 Units on a scale Standard Deviation 1.67	0.0 Units on a scale Standard Deviation 1.32
Change From Baseline in Brief Fatigue Inventory (BFI) Questionnaire Composite Scores to Months 3, 6, 12, 18 and 24 Change at month 6	1.0 Units on a scale Standard Deviation 2.03	-0.1 Units on a scale Standard Deviation 1.27
Change From Baseline in Brief Fatigue Inventory (BFI) Questionnaire Composite Scores to Months 3, 6, 12, 18 and 24 Change at month 12	1.2 Units on a scale Standard Deviation 1.94	0.1 Units on a scale Standard Deviation 1.32
Change From Baseline in Brief Fatigue Inventory (BFI) Questionnaire Composite Scores to Months 3, 6, 12, 18 and 24 Change at month 18	0.3 Units on a scale Standard Deviation 1.43	-0.2 Units on a scale Standard Deviation 1.22
Change From Baseline in Brief Fatigue Inventory (BFI) Questionnaire Composite Scores to Months 3, 6, 12, 18 and 24 Change at month 24	0.5 Units on a scale Standard Deviation 1.15	0.1 Units on a scale Standard Deviation 1.27

SECONDARY outcome

Timeframe: Baseline, months 6, 12, 18 and 24

Population: FAS population with available data at each time point.

SF-12 is a questionnaire that measures overall health related quality of life using 12 questions. The questions are then scored and weighted into 2 subscales, physical health and mental health. Each yields scores from 0 (representing the worst possible debilitation) to 100 (representing no reduction in quality of life). Scores are transformed and ranges between 0 to 100; higher score indicates improvement.

Outcome measures

Outcome measures
Measure	Enzalutamide n=114 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Change From Baseline in 12-Item Short Form Survey (SF-12) Questionnaire Composite Score to Months 6, 12, 18, 24 - Mental Component Summary Change at month 24	-0.3 Units on a scale Standard Deviation 5.27	-1.4 Units on a scale Standard Deviation 7.29
Change From Baseline in 12-Item Short Form Survey (SF-12) Questionnaire Composite Score to Months 6, 12, 18, 24 - Mental Component Summary Change at month 6	-1.6 Units on a scale Standard Deviation 5.94	-0.1 Units on a scale Standard Deviation 6.83
Change From Baseline in 12-Item Short Form Survey (SF-12) Questionnaire Composite Score to Months 6, 12, 18, 24 - Mental Component Summary Change at month 12	-2.3 Units on a scale Standard Deviation 6.70	-1.7 Units on a scale Standard Deviation 6.84
Change From Baseline in 12-Item Short Form Survey (SF-12) Questionnaire Composite Score to Months 6, 12, 18, 24 - Mental Component Summary Change at month 18	0.0 Units on a scale Standard Deviation 6.18	-0.5 Units on a scale Standard Deviation 5.24

SECONDARY outcome

Timeframe: Baseline, months 6, 12, 18 and 24

Population: FAS population with available data at each time point.

Outcome measures

Outcome measures
Measure	Enzalutamide n=114 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Change From Baseline in SF-12 Questionnaire Composite Score to Months 6, 12, 18, 24 - Physical Component Summary Change at month 6	-2.8 Units on a scale Standard Deviation 6.64	0.1 Units on a scale Standard Deviation 5.45
Change From Baseline in SF-12 Questionnaire Composite Score to Months 6, 12, 18, 24 - Physical Component Summary Change at month 12	-3.9 Units on a scale Standard Deviation 6.73	-0.9 Units on a scale Standard Deviation 5.52
Change From Baseline in SF-12 Questionnaire Composite Score to Months 6, 12, 18, 24 - Physical Component Summary Change at month 18	-3.9 Units on a scale Standard Deviation 6.37	-0.4 Units on a scale Standard Deviation 4.37
Change From Baseline in SF-12 Questionnaire Composite Score to Months 6, 12, 18, 24 - Physical Component Summary Change at month 24	-2.8 Units on a scale Standard Deviation 5.96	-1.6 Units on a scale Standard Deviation 5.42

SECONDARY outcome

Timeframe: Baseline, months 6, 12, 18 and 24

Population: FAS population with available data at each time point.

The EPIC Hormonal Assessment was a questionnaire used to measure quality of life (QoL) issues in participants with prostate cancer. There were a total of 6 questions related to hormonal function such as hot flashes, breast tenderness, depression, lack of energy, weight fluctuation. The answers ranged from "more than once a day" to "rarely or never" (ranged from 1 to 5, corresponding standardized scores were 100, 75, 50, 25, 0), "no problem" to "big problem" (ranged from 0 to 4, corresponding standardized scores were 100, 75, 50, 25, 0). Score from each answer was converted into standardized score at each visit. Total score was calculated by taking average of standardized scores. Total score was measured on a scale ranged from 0 (worst) to 100 (best) scale with higher scores representing better hormonal function.

Outcome measures

Outcome measures
Measure	Enzalutamide n=114 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Change From Baseline in The Expanded Prostate Cancer Index Composite (EPIC) Hormonal Assessment Scores at Months 6, 12, 18 and 24 Change at month 6	2.2 Units on a scale Standard Deviation 6.74	0.2 Units on a scale Standard Deviation 3.51
Change From Baseline in The Expanded Prostate Cancer Index Composite (EPIC) Hormonal Assessment Scores at Months 6, 12, 18 and 24 Change at month 12	-1.1 Units on a scale Standard Deviation 6.77	0.4 Units on a scale Standard Deviation 4.45
Change From Baseline in The Expanded Prostate Cancer Index Composite (EPIC) Hormonal Assessment Scores at Months 6, 12, 18 and 24 Change at month 18	-1.7 Units on a scale Standard Deviation 3.81	-0.5 Units on a scale Standard Deviation 4.29
Change From Baseline in The Expanded Prostate Cancer Index Composite (EPIC) Hormonal Assessment Scores at Months 6, 12, 18 and 24 Change at month 24	-1.2 Units on a scale Standard Deviation 4.93	0.6 Units on a scale Standard Deviation 3.92

SECONDARY outcome

Timeframe: Baseline, months 6, 12, 18 and 24

Population: FAS population with available data at each time point.

EPIC Sexual Assessment: a questionnaire to measure QoL issues in participants with prostate cancer, included a total of 9 questions on sexual function as level of sexual desire, ability to have an erection, ability to reach orgasm, quality and frequency of erections, frequency of sexual intercourse. Answers ranged from "very poor" to "very good,"(ranged from 1 - 5, corresponding standardized scores:0, 25, 50, 75, 100), "none" to "enough"(ranged from 1 - 4, corresponding standardized scores:0, 33, 67, 100), "no problem" to "big problem"(ranged from 0 - 4, corresponding standardized scores:100, 75, 50, 25, 0), and "never" to "daily"(ranged from 1 - 5, corresponding standardized scores:100, 75, 50, 25, 0). Scores from each answer was converted into standardized score at each visit. Total score = calculated by taking average of standardized scores. Total score was measured on a scale ranged from 0 (worst) to 100 (best), higher scores = better sexual function and satisfaction.

Outcome measures

Outcome measures
Measure	Enzalutamide n=114 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Change From Baseline in EPIC Sexual Assessment Scores at Months 6, 12, 18 and 24 Change at month 6	-26.7 Units on a scale Standard Deviation 21.91	-2.3 Units on a scale Standard Deviation 15.34
Change From Baseline in EPIC Sexual Assessment Scores at Months 6, 12, 18 and 24 Change at month 12	-30.5 Units on a scale Standard Deviation 23.31	-2.9 Units on a scale Standard Deviation 15.59
Change From Baseline in EPIC Sexual Assessment Scores at Months 6, 12, 18 and 24 Change at month 18	-9.5 Units on a scale Standard Deviation 17.41	-2.1 Units on a scale Standard Deviation 15.91
Change From Baseline in EPIC Sexual Assessment Scores at Months 6, 12, 18 and 24 Change at month 24	-12.2 Units on a scale Standard Deviation 18.35	-3.7 Units on a scale Standard Deviation 16.81

SECONDARY outcome

Timeframe: Baseline, months 6, 12, 18 and 24

Population: FAS population with available data at each time point.

EPIC urinary assessment: a questionnaire to measure QoL issues in participants with prostate cancer, included a total of 7 questions on urinary function as leaking urine, blood in urine, pain/burning on urination, urinary control and frequency. Answers ranged from "more than once a day" to "rarely or never"(scores from 1 - 5,corresponding standardized scores\[CSS\]:0, 25, 50, 75, 100), "no urinary control" to "full urinary control"(scores from 1 - 4,CSS:0, 33, 67, 100), "none" to "3 or more pads per day"(scores from 0 - 3, CSS:100, 67, 33, 0), "no problem" to "big problem"(scores from 0 - 4, CSS:100, 75, 50, 25, 0), and "no problem" to "big problem"(scores from 1 - 5, corresponding standardized score:100, 75, 50, 25, 0). Score from each answer was converted into a corresponding standardized score at each visit. Total score was calculated by taking average of standardized scores. Total score ranged from 0(worst) to 100(best), higher scores = better urinary function.

Outcome measures

Outcome measures
Measure	Enzalutamide n=114 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Change From Baseline in EPIC Urinary Assessment Scores at Month 6, 12, 18 and 24 Change at month 6	-2.7 Units on a scale Standard Deviation 10.26	0.7 Units on a scale Standard Deviation 10.28
Change From Baseline in EPIC Urinary Assessment Scores at Month 6, 12, 18 and 24 Change at month 12	-4.2 Units on a scale Standard Deviation 10.10	0.3 Units on a scale Standard Deviation 10.98
Change From Baseline in EPIC Urinary Assessment Scores at Month 6, 12, 18 and 24 Change at month 18	-1.6 Units on a scale Standard Deviation 9.55	0.2 Units on a scale Standard Deviation 12.91
Change From Baseline in EPIC Urinary Assessment Scores at Month 6, 12, 18 and 24 Change at month 24	-1.6 Units on a scale Standard Deviation 9.36	0.3 Units on a scale Standard Deviation 13.47

SECONDARY outcome

Timeframe: Baseline, months 6, 12, 18 and 24

Population: FAS population with available data at each time point.

The MAX-PC was a questionnaire used to assess participants' feelings about prostate cancer and PSA tests. There were a total of 18 questions related to understanding how participants cope with aspects of their treatment and medical tests frequently involved in their care; questions such as strong feelings about prostate cancer, scared of PSA tests, trouble sleeping due to thoughts of prostate cancer, unable to plan for the future due to prostate cancer, fear of cancer getting worse. The answers range from "not at all" to "often" and "strongly disagree" to "strongly agree. Total score ranged from 0-54, an increase in the score indicates a worsened anxiety level.

Outcome measures

Outcome measures
Measure	Enzalutamide n=114 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 Participants The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Change From Baseline in Memorial Anxiety Scale for Prostate Cancer (MAX-PC) Scores at Months 6, 12, 18 and 24 Change at month 12	-0.8 Units on a scale Standard Deviation 4.49	-0.0 Units on a scale Standard Deviation 4.52
Change From Baseline in Memorial Anxiety Scale for Prostate Cancer (MAX-PC) Scores at Months 6, 12, 18 and 24 Change at month 6	-1.6 Units on a scale Standard Deviation 6.23	-0.5 Units on a scale Standard Deviation 4.45
Change From Baseline in Memorial Anxiety Scale for Prostate Cancer (MAX-PC) Scores at Months 6, 12, 18 and 24 Change at month 18	-1.3 Units on a scale Standard Deviation 4.86	-0.6 Units on a scale Standard Deviation 4.70
Change From Baseline in Memorial Anxiety Scale for Prostate Cancer (MAX-PC) Scores at Months 6, 12, 18 and 24 Change at month 24	-1.4 Units on a scale Standard Deviation 5.19	-0.6 Units on a scale Standard Deviation 3.78

Adverse Events

Enzalutamide

Serious events: 19 serious events

Other events: 101 other events

Deaths: 3 deaths

Active Surveillance

Serious events: 10 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Disclosure

Astellas Pharma Global Development, Inc.

Phone: 800-888-7704

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
Publication restrictions are in place

Restriction type: OTHER

Measure	Enzalutamide n=112 participants at risk The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 participants at risk The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Cardiac disorders Angina pectoris	0.00% 0/112 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Cardiac disorders Arteriospasm coronary	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Cardiac disorders Atrial fibrillation	0.00% 0/112 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Cardiac disorders Cardiac tamponade	0.00% 0/112 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Cardiac disorders Coronary artery perforation	0.00% 0/112 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Cardiac disorders Myocardial infarction	2.7% 3/112 • Number of events 3 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Ear and labyrinth disorders Vertigo positional	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Gastrointestinal disorders Abdominal pain	0.00% 0/112 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Gastrointestinal disorders Enteritis	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
General disorders Accidental death	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Infections and infestations Chronic sinusitis	0.00% 0/112 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Infections and infestations Escherichia sepsis	1.8% 2/112 • Number of events 2 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Infections and infestations Pneumonia	1.8% 2/112 • Number of events 2 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Injury, poisoning and procedural complications Central cord syndrome	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Injury, poisoning and procedural complications Hip fracture	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Injury, poisoning and procedural complications Rib fracture	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Investigations Electroencephalogram abnormal	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/112 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Musculoskeletal and connective tissue disorders Osteoarthritis	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Musculoskeletal and connective tissue disorders Spinal stenosis	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/112 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.00% 0/112 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/112 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Nervous system disorders Haemorrhage intracranial	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Nervous system disorders Haemorrhagic stroke	0.00% 0/112 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Nervous system disorders Movement disorder	0.00% 0/112 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Nervous system disorders Presyncope	0.00% 0/112 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Psychiatric disorders Suicide attempt	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Renal and urinary disorders Acute kidney injury	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Reproductive system and breast disorders Prostatitis	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/112 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Social circumstances Physical disability	0.00% 0/112 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Vascular disorders Deep vein thrombosis	0.89% 1/112 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)

Measure	Enzalutamide n=112 participants at risk The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants received 160-mg enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).	Active Surveillance n=113 participants at risk The study has 3 parts: treatment period, 1 year follow-up period and continued follow-up period. Participants did not receive any study treatment in this arm but were on continued AS for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Gastrointestinal disorders Diarrhoea	5.4% 6/112 • Number of events 8 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 2 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Gastrointestinal disorders Nausea	6.2% 7/112 • Number of events 7 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
General disorders Fatigue	55.4% 62/112 • Number of events 68 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	4.4% 5/113 • Number of events 5 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Infections and infestations Upper respiratory tract infection	9.8% 11/112 • Number of events 14 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	5.3% 6/113 • Number of events 6 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Investigations Weight decreased	5.4% 6/112 • Number of events 6 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	1.8% 2/113 • Number of events 2 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Investigations Weight increased	5.4% 6/112 • Number of events 7 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Musculoskeletal and connective tissue disorders Arthralgia	8.9% 10/112 • Number of events 12 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	3.5% 4/113 • Number of events 4 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Musculoskeletal and connective tissue disorders Back pain	8.9% 10/112 • Number of events 10 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	3.5% 4/113 • Number of events 4 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Psychiatric disorders Libido decreased	8.9% 10/112 • Number of events 10 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Renal and urinary disorders Dysuria	5.4% 6/112 • Number of events 6 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	4.4% 5/113 • Number of events 7 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Renal and urinary disorders Pollakiuria	7.1% 8/112 • Number of events 8 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	3.5% 4/113 • Number of events 4 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Reproductive system and breast disorders Breast enlargement	6.2% 7/112 • Number of events 8 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Reproductive system and breast disorders Breast tenderness	25.9% 29/112 • Number of events 31 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.88% 1/113 • Number of events 1 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Reproductive system and breast disorders Erectile dysfunction	19.6% 22/112 • Number of events 22 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	3.5% 4/113 • Number of events 4 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Reproductive system and breast disorders Gynaecomastia	37.5% 42/112 • Number of events 45 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	2.7% 3/113 • Number of events 3 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Reproductive system and breast disorders Nipple pain	30.4% 34/112 • Number of events 34 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Skin and subcutaneous tissue disorders Alopecia	9.8% 11/112 • Number of events 11 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Vascular disorders Hot flush	5.4% 6/112 • Number of events 6 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	0.00% 0/113 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Vascular disorders Hypertension	8.9% 10/112 • Number of events 11 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)	8.8% 10/113 • Number of events 18 • From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020, approximately 50 months)