A Study of an Intermittent ADT Approach With Apalutamide Monotherapy in Participants With mCSPC

Severity adjusted hot flash score and hot flash frequency will be calculated from the hot flash diary which will be daily filled by the participants.

PFS2 is defined as the duration from the date of randomization to the first occurrence of investigator-determined disease progression on the first subsequent therapy after study drug discontinuation or death, whichever occurs first.

Overall survival time is defined as the duration from the date of randomization to the date of death from any cause.

Prostate cancer-specific survival is defined as the duration from the date of randomization to the date of death from prostate cancer-specific cause.

Serum PSA evaluations will be measured according to Prostate Cancer Working Group 3 (PCWG3) criteria.

Duration of time on ADT will be reported for all participants.

Time to first ADT restart will be reported.

Duration of time with testosterone level <50 ng/mL will be reported.

The testosterone recovery, defined as a serum testosterone >50 ng/dL will be analyzed.

Time to recovery of testosterone >= screening testosterone level will be reported.

Time to serum testosterone recovery to normal range (>270 ng/dL) will be reported.

Time to mCRPC will be reported.

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, or is an important medical event.

Number of participants with abnormal clinical laboratory parameters (hematology, clinical chemistry) will be reported.

Number of participants with abnormal vital sign parameters (temperature, pulse/heart rate, respiratory rate, and blood pressure) will be reported.

Number of Participants with Abnormal physical examination parameters will be reported.

The HFRDIS is a 10-item scale assessing how much hot flashes interfered with various aspects of a participant's daily life. All items are rated on a 0-10 numerical rating scale with 0 anchored as "Do Not Interfere" and 10 as "Completely Interfere." A total score is computed by summing items. Higher scores indicate higher interference due to hot flashes and thus, greater impact on quality of life.

The EORTC-QLQ-C30 (Version 3), is a self-administered, 30-item questionnaire measuring the HRQoL of participants with cancer. The recall period for most items is the past week. EORTC-QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), a global health status/quality of life scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The item and scale scores are transformed to a 0 to 100 scale. A high scale score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of functioning and a high score for the global health status represents high HRQoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.

The EORTC-PR25 questionnaire is a supplement to the EORTC-QLQ-C30 questionnaire and is designed to assess symptoms related to prostate cancer, its treatment, and aspects of life related to this type of cancer.

EORTC customized study form will include 3 questions that are not included on the QLQ-30 or PR25 forms. The items assess rash, side effect burden, and dry mouth.

The PROMIS-Cog is a self-administered fixed-length questionnaire of 8 items from the PROMIS item bank relating to cognitive function. The raw domain scores are converted to standardized T-scores with a mean of 50 and a standard deviation of 10. Higher scores indicate better cognitive functioning.

The MAX-PC is a patient-reported questionnaire measuring prostate cancer specific anxiety. It consists of 18 items in 3 domains: It includes 11 items regarding prostate cancer anxiety, scored 0-33; 3 items regarding prostate-specific Antigen Anxiety, scored 0-9; and 4 items regarding fear of recurrence, scored 0-12. Total score ranges from 0-54 with higher scores indicating greater anxiety.

The PHQ-9 is self-administered, 9-item questionnaire measuring symptoms of depression. The recall period for all items is the past 2 weeks. The items include diminished interest or pleasure, depressed mood, insomnia/hypersomnia, fatigue or loss of energy, weight loss or weight gain/appetite loss or appetite gain, feelings of worthlessness, diminished concentration/indecisiveness, psychomotor agitation/retardation, and thoughts of death/suicide. Higher scores indicate more severe depressive symptoms.

The PGIS is a self-administered, single item questionnaire measuring patients' impression of disease severity. Participants will be asked to rate their disease severity over the past 7 days using the following 5-point scale: 1 = None, 2 = Mild, 3 = Moderate, 4 = Severe, and 5 = Very severe. Higher scores indicate greater severity of fatigue.

The PGIC is self-administered, single-item questionnaire measuring patients' impression of change in disease symptoms. Participants will be asked to rate their current symptoms as compared to when they started the study, using the following 7-point scale: 1 = Much better, 2 = Moderately better, 3 = A little better, 4 = No change, 5 = A little worse, 6 = Moderately worse, and 7 = Much worse. A higher PGIC score indicates greater worsening of symptoms.

Time to recovery from baseline as assessed by EORTC-QLQ-C30 will be reported. The EORTC-QLQ-C30 (Version 3), is a self-administered, 30-item questionnaire measuring the HRQoL of participants with cancer. The recall period for most items is the past week. EORTC-QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), a global health status/quality of life scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The item and scale scores are transformed to a 0 to 100 scale. A high scale score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of functioning and a high score for the global health status represents high HRQoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.

Time to recovery from baseline as assessed by EORTC-PR25 will be reported. The EORTC-PR25 questionnaire is a supplement to the EORTC-QLQ-C30 questionnaire and is designed to assess symptoms related to prostate cancer, its treatment, and aspects of life related to this type of cancer.

Time to recovery from baseline as assessed by EORTC customized study form will be reported. EORTC customized study form will include 3 questions that are not included on the QLQ-30 or PR25 forms. The items assess rash, side effect burden, and dry mouth.

Time to recovery from baseline as assessed by MAX-PC will be reported. The MAX-PC is a patient-reported questionnaire measuring prostate cancer specific anxiety. It consists of 18 items in 3 domains: It includes 11 items regarding prostate cancer anxiety, scored 0-33; 3 items regarding prostate-specific Antigen Anxiety, scored 0-9; and 4 items regarding fear of recurrence, scored 0-12. Total score ranges from 0-54 with higher scores indicating greater anxiety.

Time to recovery from baseline as assessed by PHQ-9 will be reported. The PHQ-9 is self-administered, 9-item questionnaire measuring symptoms of depression. The recall period for all items is the past 2 weeks. The items include diminished interest or pleasure, depressed mood, insomnia/hypersomnia, fatigue or loss of energy, weight loss or weight gain/appetite loss or appetite gain, feelings of worthlessness, diminished concentration/indecisiveness, psychomotor agitation/retardation, and thoughts of death/suicide. Higher scores indicate more severe depressive symptoms.

Time to recovery from baseline as assessed by PGIS will be reported. The PGIS is a self-administered, single item questionnaire measuring patients' impression of disease severity. Participants will be asked to rate their disease severity over the past 7 days using the following 5-point scale: 1 = None, 2 = Mild, 3 = Moderate, 4 = Severe, and 5 = Very severe. Higher scores indicate greater severity of fatigue.

Time to recovery from baseline as assessed by PGIC will be reported. The PGIC is self-administered, single-item questionnaire measuring patients' impression of change in disease symptoms. Participants will be asked to rate their current symptoms as compared to when they started the study, using the following 7-point scale: 1 = Much better, 2 = Moderately better, 3 = A little better, 4 = No change, 5 = A little worse, 6 = Moderately worse, and 7 = Much worse. A higher PGIC score indicates greater worsening of symptoms.

Time to recovery from baseline as assessed by PROMIS-Cog will be reported. The PROMIS-Cog is a self-administered fixed-length questionnaire of 8 items from the PROMIS item bank relating to cognitive function. The raw domain scores are converted to standardized T-scores with a mean of 50 and a standard deviation of 10. Higher scores indicate better cognitive functioning.

Time to deterioration in EORTC-QLQ-C30 over time will be reported. The EORTC-QLQ-C30 (Version 3), is a self-administered, 30-item questionnaire measuring the HRQoL of participants with cancer. The recall period for most items is the past week. EORTC-QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), a global health status/quality of life scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The item and scale scores are transformed to a 0 to 100 scale. A high scale score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of functioning and a high score for the global health status represents high HRQoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.

Time to deterioration in EORTC-PR25 over time will be reported. The EORTC-PR25 questionnaire is a supplement to the EORTC-QLQ-C30 questionnaire and is designed to assess symptoms related to prostate cancer, its treatment, and aspects of life related to this type of cancer.

Time to deterioration in EORTC Customized Study Form over time will be reported. EORTC customized study form will include 3 questions that are not included on the QLQ-30 or PR25 forms. The items assess rash, side effect burden, and dry mouth.

Time to deterioration as per PROMIS-Cog questionnaire over time will be reported. The PROMIS-Cog is a self-administered fixed-length questionnaire of 8 items from the PROMIS item bank relating to cognitive function. The raw domain scores are converted to standardized T-scores with a mean of 50 and a standard deviation of 10. Higher scores indicate better cognitive functioning.

Time to deterioration in MAX-PC questionnaire over time will be reported. The MAX-PC is a patient-reported questionnaire measuring prostate cancer specific anxiety. It consists of 18 items in 3 domains: It includes 11 items regarding prostate cancer anxiety, scored 0-33; 3 items regarding prostate-specific Antigen Anxiety, scored 0-9; and 4 items regarding fear of recurrence, scored 0-12. Total score ranges from 0-54 with higher scores indicating greater anxiety.

Time to deterioration as per PHQ-9 questionnaire over time will be reported. The PHQ-9 is self-administered, 9-item questionnaire measuring symptoms of depression. The recall period for all items is the past 2 weeks. The items include diminished interest or pleasure, depressed mood, insomnia/hypersomnia, fatigue or loss of energy, weight loss or weight gain/appetite loss or appetite gain, feelings of worthlessness, diminished concentration/indecisiveness, psychomotor agitation/retardation, and thoughts of death/suicide. Higher scores indicate more severe depressive symptoms.

Time to deterioration as per PGIS questionnaire over time will be reported. The PGIS is a self-administered, single item questionnaire measuring patients' impression of disease severity. Participants will be asked to rate their disease severity over the past 7 days using the following 5-point scale: 1 = None, 2 = Mild, 3 = Moderate, 4 = Severe, and 5 = Very severe. Higher scores indicate greater severity of fatigue.

Time to Deterioration as per PGIC questionnaire over time will be reported. The PGIC is self-administered, single-item questionnaire measuring patients' impression of change in disease symptoms. Participants will be asked to rate their current symptoms as compared to when they started the study, using the following 7-point scale: 1 = Much better, 2 = Moderately better, 3 = A little better, 4 = No change, 5 = A little worse, 6 = Moderately worse, and 7 = Much worse. A higher PGIC score indicates greater worsening of symptoms.