Prostate Cancer
Conditions
Keywords
enzalutamide, Xtandi, Prostate Cancer
Brief summary
The objective of this study was to compare the efficacy and safety of the combination therapy with enzalutamide + androgen deprivation therapy (ADT) and the combination therapy with flutamide + ADT in patients with castration resistant prostate cancer who had relapsed during combined androgen blockade (CAB) therapy with bicalutamide and ADT. This study also investigated the order of alternative antiandrogen therapy (AAT) by changing the 1st line medication after relapse of prostate-specific antigen (PSA).
Interventions
DRUGEnzalutamide
Oral Capsule
DRUGFlutamide
Oral tablet
OTHERAndrogen deprivation therapy
All subjects must undergo continuous Androgen deprivation therapy with GnRH agonist/antagonist or bilateral orchiectomy during the study period.
Sponsors
Pfizer
Astellas Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is diagnosed with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small-cell histology. * Subject on continuous ADT with Gonadotropin Releasing Hormone (GnRH) agonist/antagonist or bilateral orchiectomy. * Serum testosterone level below the target level at screening visit. * Subject with asymptomatic or mildly symptomatic prostate cancer. * Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Subject has progression of the disease as defined by rising PSA levels or progressive soft tissue or bony disease during CAB therapy in combination of bicalutamide and ADT. * A sexually active male subject and the subject's female partner who is of childbearing potential must use 2 acceptable birth control methods from screening to 3 months after the last dose of the study drug. * Subject must agree not to donate sperm from screening to 3 months after the last dose of the study drug.
Exclusion criteria
* Subject with severe concurrent diseases, infections, or complications. * Subject with confirmed or suspected brain metastasis or active leptomeningeal metastasis. * Subject with a history of malignant tumor other than prostate cancer in the past 5 years. * Subject hypersensitive to the ingredients of enzalutamide capsules or flutamide tablets. * Subject with a history of convulsive attack, or prone to convulsive attack. * Subject with liver disorder such as viral hepatitis and hepatic cirrhosis, or subject with Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) at screening visit higher than the upper limit of normal. * Subject received treatment for prostate cancer with cytocidal chemotherapy that includes anti androgenic agents other than bicalutamide, abiraterone, or estramustine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to PSA Progression With 1st Line AAT (TTPP1) | From date of randomization to the date of PSA progression in the 1st line AAT period (Up to 38 months) | TTPP1 was defined as the period from the date of randomization to the date of PSA progression in the 1st line AAT period. PSA progression was defined according to the consensus guidelines of prostate cancer clinical trials working group 2 (PCWG2). For participants with PSA declines at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir were documented, which was confirmed by a second consecutive value obtained 3 or more weeks later. For participants with no PSA decline at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the baseline were documented. Time to event analysis was performed using kaplan-meier (KM) estimates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | Baseline and at least 3 weeks after, the lowest PSA decreased by at least 50% or 90% from baseline (Up to 38 months) | PSA response was defined as PSA decreased by at least 50% or 90% from baseline when at least 3 weeks passed after the lowest PSA decreased by at least 50% or 90% from baseline in the 1st line AAT period after baseline. Data was reported per each disease stage (M0/N0, M0/N1, M1). 1) M0/N0: No distant metastasis and no lymph node metastasis. 2) M0/N1: Without distant metastasis, but with metastasis in lymph nodes distal to the aortic bifurcation. 3) M1: With distant metastasis (including metastasis in lymph nodes proximal to the aortic bifurcation). |
| Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | Baseline and week 13 | PSA response was defined as the lowest PSA at week 13 decreased by at least 50% or 90% from baseline in the 1st line AAT period. Data was reported per each disease stage (M0/N0, M0/N1, M1). 1) M0/N0: No distant metastasis and no lymph node metastasis. 2) M0/N1: Without distant metastasis, but with metastasis in lymph nodes distal to the aortic bifurcation. 3) M1: With distant metastasis (including metastasis in lymph nodes proximal to the aortic bifurcation). |
| Time to PSA Decrease by 50% From Baseline With 1st Line AAT | From date of randomization to the day when the decrease of PSA from baseline by 50% is first identified (Up to 38 months) | Time to PSA decrease by 50% with 1st line AAT was defined as the period from the date of randomization to the day when the decrease of PSA from baseline by 50% is first identified. Time to event analysis was performed using kaplan-meier estimates. Data was reported per each disease stage (M0/N0, M0/N1, M1). 1) M0/N0: No distant metastasis and no lymph node metastasis. 2) M0/N1: Without distant metastasis, but with metastasis in lymph nodes distal to the aortic bifurcation. 3) M1: With distant metastasis (including metastasis in lymph nodes proximal to the aortic bifurcation). |
| Time to PSA Progression With 2nd Line AAT (TTPP2) | From date of randomization to the date of PSA progression in 2nd line AAT (Up to 38 months) | TTPP2 was defined as the period from day 1 of the 2nd line AAT to the date of PSA progression with the 2nd line AAT. PSA progression was defined according to the consensus guidelines of PCWG2. For participants with PSA declines at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir were documented, which was confirmed by a second consecutive value obtained 3 or more weeks later. For participants with no PSA decline at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the baseline were documented. Time to event analysis was performed using kaplan-meier estimates. |
| Time to Treatment Failure of 2nd Line AAT (TTF2) | From date of randomization to discontinuation of 2nd line AAT (Up to 38 months) | TTF2 was defined as the period from randomization to study drug discontinuation of 2nd line AAT for any reason that includes disease progression, onset of AEs, participants request, or death. Time to event analysis was performed using kaplan-meier estimates. |
| Radiographic Progression-free Survival (rPFS) | From date of randomization to the time when radiographic disease progression is observed or death of any cause (up to 38 months) | rPFS was defined as the period from randomization to the time when radiographic disease progression is observed or death of any cause during the study period, whichever occurs earlier. Time to event analysis was performed using kaplan-meier estimates. Data was reported per each disease stage (M0/N0, M0/N1, M1). 1) M0/N0: No distant metastasis and no lymph node metastasis. 2) M0/N1: Without distant metastasis, but with metastasis in lymph nodes distal to the aortic bifurcation. 3) M1: With distant metastasis (including metastasis in lymph nodes proximal to the aortic bifurcation). |
| Time to Treatment Failure of 1st Line AAT (TTF1) | From date of randomization to discontinuation of 1st line AAT (Up to 38 months) | TTF1 was defined as the period from randomization to study drug discontinuation of 1st line AAT for any reason that includes disease progression, onset of adverse events (AEs), participants request, or death. Time to event analysis was performed using kaplan-meier estimates. Data was reported per each disease stage (M0/N0, M0/N1, M1). 1) M0/N0: No distant metastasis and no lymph node metastasis. 2) M0/N1: Without distant metastasis, but with metastasis in lymph nodes distal to the aortic bifurcation. 3) M1: With distant metastasis (including metastasis in lymph nodes proximal to the aortic bifurcation). |
Countries
Japan
Participant flow
Recruitment details
Participants with M0 or M1 castration-resistant prostatic neoplasm that relapsed during Combined Androgen Blockade (CAB) therapy with bicalutamide were enrolled in this study.
Pre-assignment details
Randomization was stratified by disease stages (M0/N0, M0/N1 or M1).
Participants by arm
| Arm | Count |
|---|---|
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT Participants received enzalutamide 160 mg capsules, orally once daily as 1st line of AAT until confirmed PSA progression, other disease progression, or an intolerable adverse event. After confirmed PSA progression, other disease progression, or an intolerable adverse event, participants received flutamide 125 mg tablets orally thrice daily after each meal as 2nd line of AAT. Treatment with each drug was continued until the participant met any of the discontinuation criteria or until 2 years from the enrollment of the last participant (approximately 38 months). | 102 |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT Participants received flutamide 125 mg tablets orally thrice daily after each meal as 1st line of AAT until confirmed PSA progression, other disease progression, or an intolerable adverse event. After confirmed PSA progression, other disease progression, or an intolerable adverse event, participants received enzalutamide 160 mg capsules orally once daily as 2nd line of AAT. Treatment with each drug was continued until the participant met any of the discontinuation criteria or until 2 years from the enrollment of the last participant (approximately 38 months). | 104 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 1st Line AAT | Adverse Event | 12 | 3 |
| 1st Line AAT | Death | 1 | 0 |
| 1st Line AAT | Lost to Follow-up | 0 | 1 |
| 1st Line AAT | Miscellaneous | 1 | 0 |
| 1st Line AAT | Physician Decision | 4 | 2 |
| 1st Line AAT | Progressive disease | 9 | 4 |
| 1st Line AAT | Withdrawal by Subject | 2 | 1 |
| 2nd Line AAT | Adverse Event | 2 | 5 |
| 2nd Line AAT | Death | 0 | 1 |
| 2nd Line AAT | Physician Decision | 0 | 1 |
| 2nd Line AAT | Progressive disease | 21 | 3 |
| 2nd Line AAT | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Total |
|---|---|---|---|
| Age, Continuous | 74.4 years STANDARD_DEVIATION 7.6 | 74.1 years STANDARD_DEVIATION 7.6 | 74.2 years STANDARD_DEVIATION 7.6 |
| Disease Stages at Randomization M0/N0 | 24 Participants | 25 Participants | 49 Participants |
| Disease Stages at Randomization M0/N1 | 3 Participants | 4 Participants | 7 Participants |
| Disease Stages at Randomization M1 | 75 Participants | 75 Participants | 150 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 102 Participants | 104 Participants | 206 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 102 | 1 / 85 | 0 / 104 | 0 / 48 |
| other Total, other adverse events | 79 / 102 | 56 / 85 | 65 / 104 | 22 / 48 |
| serious Total, serious adverse events | 29 / 102 | 18 / 85 | 15 / 104 | 4 / 48 |
Outcome results
Primary
Time to PSA Progression With 1st Line AAT (TTPP1)
TTPP1 was defined as the period from the date of randomization to the date of PSA progression in the 1st line AAT period. PSA progression was defined according to the consensus guidelines of prostate cancer clinical trials working group 2 (PCWG2). For participants with PSA declines at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir were documented, which was confirmed by a second consecutive value obtained 3 or more weeks later. For participants with no PSA decline at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the baseline were documented. Time to event analysis was performed using kaplan-meier (KM) estimates.
Time frame: From date of randomization to the date of PSA progression in the 1st line AAT period (Up to 38 months)
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Time to PSA Progression With 1st Line AAT (TTPP1) | 21.39 Months |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Time to PSA Progression With 1st Line AAT (TTPP1) | 5.78 Months |
p-value: <0.00195% CI: [0.29, 0.61]Log Rank
Secondary
Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT
PSA response was defined as PSA decreased by at least 50% or 90% from baseline when at least 3 weeks passed after the lowest PSA decreased by at least 50% or 90% from baseline in the 1st line AAT period after baseline. Data was reported per each disease stage (M0/N0, M0/N1, M1). 1) M0/N0: No distant metastasis and no lymph node metastasis. 2) M0/N1: Without distant metastasis, but with metastasis in lymph nodes distal to the aortic bifurcation. 3) M1: With distant metastasis (including metastasis in lymph nodes proximal to the aortic bifurcation).
Time frame: Baseline and at least 3 weeks after, the lowest PSA decreased by at least 50% or 90% from baseline (Up to 38 months)
Population: ITT population with participants in each disease stage.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N0: (≥ 50% reduction) | 75.0 Percentage of participants |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N1: (≥ 50% reduction) | 66.7 Percentage of participants |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M1: (≥ 50% reduction) | 72.0 Percentage of participants |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | All participants: (≥ 50% reduction) | 72.5 Percentage of participants |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N0: (≥ 90% reduction) | 62.5 Percentage of participants |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N1: (≥ 90% reduction) | 33.3 Percentage of participants |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M1: (≥ 90% reduction) | 53.3 Percentage of participants |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | All participants: (≥ 90% reduction) | 54.9 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | All participants: (≥ 90% reduction) | 16.3 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N0: (≥ 50% reduction) | 48.0 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N0: (≥ 90% reduction) | 8.0 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N1: (≥ 50% reduction) | 0.0 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M1: (≥ 90% reduction) | 20.0 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M1: (≥ 50% reduction) | 32.0 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N1: (≥ 90% reduction) | 0.0 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline and Up To Week 38 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | All participants: (≥ 50% reduction) | 34.6 Percentage of participants |
Comparison: \>=50% reductionp-value: <0.00195% CI: [25.2, 50.4]Mantel Haenszel
Comparison: ≥ 90% reductionp-value: <0.00195% CI: [26.3, 50.4]Mantel Haenszel
Secondary
Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT
PSA response was defined as the lowest PSA at week 13 decreased by at least 50% or 90% from baseline in the 1st line AAT period. Data was reported per each disease stage (M0/N0, M0/N1, M1). 1) M0/N0: No distant metastasis and no lymph node metastasis. 2) M0/N1: Without distant metastasis, but with metastasis in lymph nodes distal to the aortic bifurcation. 3) M1: With distant metastasis (including metastasis in lymph nodes proximal to the aortic bifurcation).
Time frame: Baseline and week 13
Population: ITT population with participants in each disease stage.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N0: (≥ 50% reduction) | 83.3 Percentage of participants |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N1: (≥ 50% reduction) | 66.7 Percentage of participants |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M1: (≥ 50% reduction) | 72.0 Percentage of participants |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | All participants: (≥ 50% reduction) | 74.5 Percentage of participants |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N0: (≥ 90% reduction) | 50.0 Percentage of participants |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N1: (≥ 90% reduction) | 33.3 Percentage of participants |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M1: (≥ 90% reduction) | 49.3 Percentage of participants |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | All participants: (≥ 90% reduction) | 49.0 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | All participants: (≥ 90% reduction) | 15.4 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N0: (≥ 50% reduction) | 40.0 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N0: (≥ 90% reduction) | 8.0 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N1: (≥ 50% reduction) | 0.0 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M1: (≥ 90% reduction) | 18.7 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M1: (≥ 50% reduction) | 33.3 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | M0/N1: (≥ 90% reduction) | 0.0 Percentage of participants |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Percentage of Participants Achieving at Least 50 or 90 Percent (%) Reduction From Baseline to Week 13 in Prostate Specific Antigen (PSA) Response at 1st Line AAT | All participants: (≥ 50% reduction) | 33.7 Percentage of participants |
Comparison: ≥ 50% reductionp-value: <0.00195% CI: [28.3, 53.1]Mantel Haenszel
Comparison: ≥90% reductionp-value: <0.00195% CI: [21.5, 45.4]Mantel Haenszel
Secondary
Radiographic Progression-free Survival (rPFS)
rPFS was defined as the period from randomization to the time when radiographic disease progression is observed or death of any cause during the study period, whichever occurs earlier. Time to event analysis was performed using kaplan-meier estimates. Data was reported per each disease stage (M0/N0, M0/N1, M1). 1) M0/N0: No distant metastasis and no lymph node metastasis. 2) M0/N1: Without distant metastasis, but with metastasis in lymph nodes distal to the aortic bifurcation. 3) M1: With distant metastasis (including metastasis in lymph nodes proximal to the aortic bifurcation).
Time frame: From date of randomization to the time when radiographic disease progression is observed or death of any cause (up to 38 months)
Population: ITT population with M1 diseases stage participants. No data reported for M0/N0 and M0/N1 as there are zero participants with event.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Radiographic Progression-free Survival (rPFS) | M1 | NA Months |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Radiographic Progression-free Survival (rPFS) | M1 | NA Months |
| Unknown | Radiographic Progression-free Survival (rPFS) | M0/N0 | — Months |
| Unknown | Radiographic Progression-free Survival (rPFS) | M0/N1 | — Months |
p-value: 0.66995% CI: [0.45, 1.67]Log Rank
Secondary
Time to PSA Decrease by 50% From Baseline With 1st Line AAT
Time to PSA decrease by 50% with 1st line AAT was defined as the period from the date of randomization to the day when the decrease of PSA from baseline by 50% is first identified. Time to event analysis was performed using kaplan-meier estimates. Data was reported per each disease stage (M0/N0, M0/N1, M1). 1) M0/N0: No distant metastasis and no lymph node metastasis. 2) M0/N1: Without distant metastasis, but with metastasis in lymph nodes distal to the aortic bifurcation. 3) M1: With distant metastasis (including metastasis in lymph nodes proximal to the aortic bifurcation).
Time frame: From date of randomization to the day when the decrease of PSA from baseline by 50% is first identified (Up to 38 months)
Population: ITT population with participants in each disease stage.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Time to PSA Decrease by 50% From Baseline With 1st Line AAT | M0/N0 | 2.79 Months |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Time to PSA Decrease by 50% From Baseline With 1st Line AAT | M0/N1 | 2.79 Months |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Time to PSA Decrease by 50% From Baseline With 1st Line AAT | M1 | 2.79 Months |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Time to PSA Decrease by 50% From Baseline With 1st Line AAT | M0/N0 | 3.94 Months |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Time to PSA Decrease by 50% From Baseline With 1st Line AAT | M0/N1 | NA Months |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Time to PSA Decrease by 50% From Baseline With 1st Line AAT | M1 | 7.49 Months |
p-value: <0.001Log Rank
Secondary
Time to PSA Progression With 2nd Line AAT (TTPP2)
TTPP2 was defined as the period from day 1 of the 2nd line AAT to the date of PSA progression with the 2nd line AAT. PSA progression was defined according to the consensus guidelines of PCWG2. For participants with PSA declines at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir were documented, which was confirmed by a second consecutive value obtained 3 or more weeks later. For participants with no PSA decline at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the baseline were documented. Time to event analysis was performed using kaplan-meier estimates.
Time frame: From date of randomization to the date of PSA progression in 2nd line AAT (Up to 38 months)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Time to PSA Progression With 2nd Line AAT (TTPP2) | NA Months |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Time to PSA Progression With 2nd Line AAT (TTPP2) | 21.22 Months |
Secondary
Time to Treatment Failure of 1st Line AAT (TTF1)
TTF1 was defined as the period from randomization to study drug discontinuation of 1st line AAT for any reason that includes disease progression, onset of adverse events (AEs), participants request, or death. Time to event analysis was performed using kaplan-meier estimates. Data was reported per each disease stage (M0/N0, M0/N1, M1). 1) M0/N0: No distant metastasis and no lymph node metastasis. 2) M0/N1: Without distant metastasis, but with metastasis in lymph nodes distal to the aortic bifurcation. 3) M1: With distant metastasis (including metastasis in lymph nodes proximal to the aortic bifurcation).
Time frame: From date of randomization to discontinuation of 1st line AAT (Up to 38 months)
Population: ITT population with participants in each disease stage.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Time to Treatment Failure of 1st Line AAT (TTF1) | M0/N0 | 17.58 Months |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Time to Treatment Failure of 1st Line AAT (TTF1) | M0/N1 | 5.55 Months |
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Time to Treatment Failure of 1st Line AAT (TTF1) | M1 | 12.02 Months |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Time to Treatment Failure of 1st Line AAT (TTF1) | M0/N0 | 7.72 Months |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Time to Treatment Failure of 1st Line AAT (TTF1) | M0/N1 | 4.73 Months |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Time to Treatment Failure of 1st Line AAT (TTF1) | M1 | 3.94 Months |
p-value: <0.001Log Rank
Secondary
Time to Treatment Failure of 2nd Line AAT (TTF2)
TTF2 was defined as the period from randomization to study drug discontinuation of 2nd line AAT for any reason that includes disease progression, onset of AEs, participants request, or death. Time to event analysis was performed using kaplan-meier estimates.
Time frame: From date of randomization to discontinuation of 2nd line AAT (Up to 38 months)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Time to Treatment Failure of 2nd Line AAT (TTF2) | 23.03 Months |
| Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT | Time to Treatment Failure of 2nd Line AAT (TTF2) | 16.59 Months |