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

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.

Time frame: 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

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.

Time frame: Baseline, months 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.

Time frame: Baseline, months 3, 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline, months 6, 12, 18 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.

Time frame: Baseline, months 12 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.

Time frame: 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.

Time frame: Baseline, months 6, 12, 18 and 24

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

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.

Time frame: 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.

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

Time frame: At the end of months 12 and 24

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.

Time frame: 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.

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.

Time frame: 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