Study on Enzalutamide and Flutamide in Patients With Castration Resistant Prostate Cancer
Study Details
Study Description
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).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 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 alternative antiandrogen therapy (AAT) until confirmed prostate-specific antigen (PSA) progression, other disease progression, or an intolerable adverse event. After confirmation of 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). |
Drug: Enzalutamide
Oral Capsule
Other Names:
Drug: Flutamide
Oral tablet
Other: Androgen deprivation therapy
All subjects must undergo continuous Androgen deprivation therapy with GnRH agonist/antagonist or bilateral orchiectomy during the study period.
|
Experimental: 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). |
Drug: Enzalutamide
Oral Capsule
Other Names:
Drug: Flutamide
Oral tablet
Other: Androgen deprivation therapy
All subjects must undergo continuous Androgen deprivation therapy with GnRH agonist/antagonist or bilateral orchiectomy during the study period.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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 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).
- 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).
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Site JP00024 | Nagoya | Aichi | Japan | |
2 | Site JP00025 | Nagoya | Aichi | Japan | |
3 | Site JP00038 | Matsuyama | Ehime | Japan | |
4 | Site JP00051 | Iizuka | Fukuoka | Japan | |
5 | Site JP00045 | Isesaki | Gunma | Japan | |
6 | Site JP00005 | Maebashi | Gunma | Japan | |
7 | Site JP00043 | Ota | Gunma | Japan | |
8 | Site JP00054 | Hakodate | Hokkaido | Japan | |
9 | Site JP00001 | Sapporo | Hokkaido | Japan | |
10 | Site JP00002 | Sapporo | Hokkaido | Japan | |
11 | Site JP00048 | Sapporo | Hokkaido | Japan | |
12 | Site JP00055 | Mito | Ibaraki | Japan | |
13 | Site JP00019 | Sagamihara | Kanagawa | Japan | |
14 | Site JP00020 | Yokohama | Kanagawa | Japan | |
15 | Site JP00021 | Yokohama | Kanagawa | Japan | |
16 | Site JP00044 | Yokosuka | Kanagawa | Japan | |
17 | Site JP00046 | Kashihara | Nara | Japan | |
18 | Site JP00033 | Kurashiki | Okayama | Japan | |
19 | Site JP00028 | Hirakata | Osaka | Japan | |
20 | Site JP00030 | Osakasayama | Osaka | Japan | |
21 | Site JP00027 | Suita | Osaka | Japan | |
22 | Site JP00009 | Kitaadachi-gun | Saitama | Japan | |
23 | Site JP00022 | Hamamatsu | Shizuoka | Japan | |
24 | Site JP00049 | Utsunomiya | Tochigi | Japan | |
25 | Site JP00011 | Bunkyo-ku | Tokyo | Japan | |
26 | Site JP00017 | Bunkyo-ku | Tokyo | Japan | |
27 | Site JP00013 | Koto-ku | Tokyo | Japan | |
28 | Site JP00014 | Nakano-ku | Tokyo | Japan | |
29 | Site JP00016 | Shinagawa-ku | Tokyo | Japan | |
30 | Site JP00018 | Shinjuku-ku | Tokyo | Japan | |
31 | Site JP00034 | Ube | Yamaguchi | Japan | |
32 | Site JP00010 | Chiba | Japan | ||
33 | Site JP00053 | Chiba | Japan | ||
34 | Site JP00039 | Fukuoka | Japan | ||
35 | Site JP00040 | Fukuoka | Japan | ||
36 | Site JP00050 | Fukuoka | Japan | ||
37 | Site JP00035 | Hiroshima | Japan | ||
38 | Site JP00026 | Kyoto | Japan | ||
39 | Site JP00006 | Nagano | Japan | ||
40 | Site JP00008 | Nagano | Japan | ||
41 | Site JP00041 | Nagasaki | Japan | ||
42 | Site JP00029 | Osaka | Japan | ||
43 | Site JP00031 | Osaka | Japan | ||
44 | Site JP00032 | Osaka | Japan | ||
45 | Site JP00042 | Saga | Japan | ||
46 | Site JP00037 | Tokushima | Japan | ||
47 | Site JP00052 | Toyama | Japan |
Sponsors and Collaborators
- Astellas Pharma Inc
- Pfizer
Investigators
- Study Director: Medical Director, Astellas Pharma Inc
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 9785-MA-3051
Study Results
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 Detail | Randomization was stratified by disease stages (M0/N0, M0/N1 or M1). |
Arm/Group Title | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Arm/Group Description | Participants received enzalutamide 160 mg capsules, orally once daily as 1st line of alternative antiandrogen therapy (AAT) until confirmed prostate-specific antigen (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). | 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). |
Period Title: 1st Line AAT | ||
STARTED | 102 | 104 |
Maintained 1st Line AAT Without Progression | 25 | 8 |
COMPLETED | 73 | 93 |
NOT COMPLETED | 29 | 11 |
Period Title: 1st Line AAT | ||
STARTED | 48 | 85 |
COMPLETED | 23 | 73 |
NOT COMPLETED | 25 | 12 |
Baseline Characteristics
Arm/Group Title | 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 |
---|---|---|---|
Arm/Group Description | 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). | 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). | Total of all reporting groups |
Overall Participants | 102 | 104 | 206 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
74.4
(7.6)
|
74.1
(7.6)
|
74.2
(7.6)
|
Sex: Female, Male (Count of Participants) | |||
Female |
0
0%
|
0
0%
|
0
0%
|
Male |
102
100%
|
104
100%
|
206
100%
|
Race and Ethnicity Not Collected (Count of Participants) | |||
Count of Participants [Participants] |
0
0%
|
||
Disease Stages at Randomization (Number) [Number] | |||
M0/N0 |
24
23.5%
|
25
24%
|
49
23.8%
|
M0/N1 |
3
2.9%
|
4
3.8%
|
7
3.4%
|
M1 |
75
73.5%
|
75
72.1%
|
150
72.8%
|
Outcome Measures
Title | Time to PSA Progression With 1st Line AAT (TTPP1) |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population |
Arm/Group Title | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Arm/Group Description | 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). | 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). |
Measure Participants | 102 | 104 |
Median (95% Confidence Interval) [Months] |
21.39
|
5.78
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT, Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | The significance level was 0.05 (two-sided). | |
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | P-value is based on a log-rank test stratified disease stages (M0/N0, M0/N1, or M1). | |
Method | Log Rank | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.42 | |
Confidence Interval |
(2-Sided) 95% 0.29 to 0.61 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Hazard ratio and P-value calculated using unstratified Cox proportional hazards model with treatment and disease stages (M0/N0, M0/N1, or M1) as covariate. |
Title | Time to PSA Progression With 2nd Line AAT (TTPP2) |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
ITT population |
Arm/Group Title | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Arm/Group Description | 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). | 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). |
Measure Participants | 102 | 104 |
Median (95% Confidence Interval) [Months] |
NA
|
21.22
|
Title | 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 |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
ITT population with participants in each disease stage. |
Arm/Group Title | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Arm/Group Description | 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). | 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). |
Measure Participants | 102 | 104 |
M0/N0: (≥ 50% reduction) |
75.0
73.5%
|
48.0
46.2%
|
M0/N1: (≥ 50% reduction) |
66.7
65.4%
|
0.0
0%
|
M1: (≥ 50% reduction) |
72.0
70.6%
|
32.0
30.8%
|
All participants: (≥ 50% reduction) |
72.5
71.1%
|
34.6
33.3%
|
M0/N0: (≥ 90% reduction) |
62.5
61.3%
|
8.0
7.7%
|
M0/N1: (≥ 90% reduction) |
33.3
32.6%
|
0.0
0%
|
M1: (≥ 90% reduction) |
53.3
52.3%
|
20.0
19.2%
|
All participants: (≥ 90% reduction) |
54.9
53.8%
|
16.3
15.7%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT, Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Comments | >=50% reduction | |
Type of Statistical Test | Superiority | |
Comments | The significance level was 0.05 (two-sided). | |
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | P-value is based on Cochran-Mantel-Haenszel mean score test stratified disease stages (M0/N0, M0/N1, or M1). | |
Method | Mantel Haenszel | |
Comments | Mantel Haenszel common risk difference | |
Method of Estimation | Estimation Parameter | Risk Difference (RD) |
Estimated Value | 37.8 | |
Confidence Interval |
(2-Sided) 95% 25.2 to 50.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Difference of response rate. |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT, Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Comments | ≥ 90% reduction | |
Type of Statistical Test | Superiority | |
Comments | The significance level was 0.05 (two-sided). | |
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | P-value is based on Cochran-Mantel-Haenszel mean score test stratified disease stages (M0/N0, M0/N1, or M1). | |
Method | Mantel Haenszel | |
Comments | Mantel Haenszel common risk difference | |
Method of Estimation | Estimation Parameter | Risk Difference (RD) |
Estimated Value | 38.4 | |
Confidence Interval |
(2-Sided) 95% 26.3 to 50.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Difference of response rate |
Title | 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 |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
ITT population with participants in each disease stage. |
Arm/Group Title | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Arm/Group Description | 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). | 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). |
Measure Participants | 102 | 104 |
M0/N0: (≥ 50% reduction) |
83.3
81.7%
|
40.0
38.5%
|
M0/N1: (≥ 50% reduction) |
66.7
65.4%
|
0.0
0%
|
M1: (≥ 50% reduction) |
72.0
70.6%
|
33.3
32%
|
All participants: (≥ 50% reduction) |
74.5
73%
|
33.7
32.4%
|
M0/N0: (≥ 90% reduction) |
50.0
49%
|
8.0
7.7%
|
M0/N1: (≥ 90% reduction) |
33.3
32.6%
|
0.0
0%
|
M1: (≥ 90% reduction) |
49.3
48.3%
|
18.7
18%
|
All participants: (≥ 90% reduction) |
49.0
48%
|
15.4
14.8%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT, Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Comments | ≥ 50% reduction | |
Type of Statistical Test | Superiority | |
Comments | The significance level was 0.05 (two-sided). | |
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | P-value is based on Cochran-Mantel-Haenszel mean score test stratified disease stages (M0/N0, M0/N1, or M1). | |
Method | Mantel Haenszel | |
Comments | Mantel Haenszel common risk difference | |
Method of Estimation | Estimation Parameter | Risk Difference (RD) |
Estimated Value | 40.7 | |
Confidence Interval |
(2-Sided) 95% 28.3 to 53.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Difference of response rate. |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT, Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Comments | ≥90% reduction | |
Type of Statistical Test | Superiority | |
Comments | The significance level was 0.05 (two-sided). | |
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | P-value is based on Cochran-Mantel-Haenszel mean score test stratified disease stages (M0/N0, M0/N1, or M1). | |
Method | Mantel Haenszel | |
Comments | Mantel Haenszel common risk difference | |
Method of Estimation | Estimation Parameter | Risk Difference (RD) |
Estimated Value | 33.5 | |
Confidence Interval |
(2-Sided) 95% 21.5 to 45.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Difference of response rate |
Title | Time to PSA Decrease by 50% From Baseline With 1st Line AAT |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
ITT population with participants in each disease stage. |
Arm/Group Title | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Arm/Group Description | 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). | 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). |
Measure Participants | 102 | 104 |
M0/N0 |
2.79
|
3.94
|
M0/N1 |
2.79
|
NA
|
M1 |
2.79
|
7.49
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT, Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | The significance level was 0.05 (two-sided). | |
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | P-value is based on a log-rank test stratified disease stages (M0/N0, M0/N1, or M1). | |
Method | Log Rank | |
Comments |
Title | Time to Treatment Failure of 1st Line AAT (TTF1) |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
ITT population with participants in each disease stage. |
Arm/Group Title | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Arm/Group Description | 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). | 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). |
Measure Participants | 102 | 104 |
M0/N0 |
17.58
|
7.72
|
M0/N1 |
5.55
|
4.73
|
M1 |
12.02
|
3.94
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT, Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | The significance level was 0.05 (two-sided). | |
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | P-value is based on a log-rank test stratified disease stages (M0/N0, M0/N1, or M1). | |
Method | Log Rank | |
Comments |
Title | Time to Treatment Failure of 2nd Line AAT (TTF2) |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
ITT population |
Arm/Group Title | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Arm/Group Description | 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). | 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). |
Measure Participants | 102 | 104 |
Median (95% Confidence Interval) [Months] |
23.03
|
16.59
|
Title | Radiographic Progression-free Survival (rPFS) |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
ITT population with M1 diseases stage participants. No data reported for M0/N0 and M0/N1 as there are zero participants with event. |
Arm/Group Title | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT | Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Arm/Group Description | 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). | 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). |
Measure Participants | 75 | 104 |
M1 |
NA
|
NA
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Enzalutamide 160 mg 1st Line AAT/Flutamide 375 mg 2nd Line AAT, Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | The significance level was 0.05 (two-sided). | |
Statistical Test of Hypothesis | p-Value | 0.669 |
Comments | P-value is based on a log-rank test stratified disease stages (M0/N0, M0/N1, or M1) | |
Method | Log Rank | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.87 | |
Confidence Interval |
(2-Sided) 95% 0.45 to 1.67 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Hazard ratio and P-value calculated using unstratified Cox proportional hazards model with treatment and disease stages (M0/N0, M0/N1, or M1) as covariate. |
Adverse Events
Time Frame | From of date of randomization to end of study (up to 38 months) | |||||||
---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||||
Arm/Group Title | Enzalutamide 160mg 1st Line AAT | Enzalutamide 160mg 2nd Line AAT | Flutamide 375mg 1st Line AAT | Flutamide 375mg 2nd Line AAT | ||||
Arm/Group Description | Participants received enzalutamide 160mg capsules orally once daily as 1st line of AAT until confirmed PSA progression, other disease progression, or an intolerable adverse event (approximately 38 months). | Participants received enzalutamide 160mg capsules orally once daily as 2nd line of AAT after confirmed PSA progression, other disease progression, or an intolerable adverse event (approximately 38 months). | Participants received flutamide 125mg tablets orally thrice daily after each meal as 1st line of AAT until confirmed PSA progression, other disease progression, or an intolerable adverse event (approximately 38 months). | Participants received flutamide 125mg tablets orally thrice daily as 2nd line of AAT after confirmed PSA progression, other disease progression, or an intolerable adverse event (approximately 38 months). | ||||
All Cause Mortality |
||||||||
Enzalutamide 160mg 1st Line AAT | Enzalutamide 160mg 2nd Line AAT | Flutamide 375mg 1st Line AAT | Flutamide 375mg 2nd Line AAT | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/102 (1%) | 1/85 (1.2%) | 0/104 (0%) | 0/48 (0%) | ||||
Serious Adverse Events |
||||||||
Enzalutamide 160mg 1st Line AAT | Enzalutamide 160mg 2nd Line AAT | Flutamide 375mg 1st Line AAT | Flutamide 375mg 2nd Line AAT | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 29/102 (28.4%) | 18/85 (21.2%) | 15/104 (14.4%) | 4/48 (8.3%) | ||||
Blood and lymphatic system disorders | ||||||||
Anaemia | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Pancytopenia | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Cardiac disorders | ||||||||
Acute myocardial infarction | 1/102 (1%) | 1 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Angina pectoris | 1/102 (1%) | 1 | 1/85 (1.2%) | 1 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Atrial fibrillation | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Cardiac failure | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 1/48 (2.1%) | 1 |
Cardiac failure acute | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Coronary artery stenosis | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Eye disorders | ||||||||
Cataract | 1/102 (1%) | 2 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Gastrointestinal disorders | ||||||||
Abdominal discomfort | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Diverticulum intestinal | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Gastric ulcer haemorrhage | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Ileus paralytic | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 1/48 (2.1%) | 1 |
Inguinal hernia | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Large intestine polyp | 0/102 (0%) | 0 | 2/85 (2.4%) | 2 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
General disorders | ||||||||
Pyrexia | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Hepatobiliary disorders | ||||||||
Hepatic function abnormal | 1/102 (1%) | 1 | 2/85 (2.4%) | 2 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Liver disorder | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Infections and infestations | ||||||||
Appendicitis | 0/102 (0%) | 0 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Enterocolitis bacterial | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Periodontitis | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 1/104 (1%) | 2 | 0/48 (0%) | 0 |
Pneumonia | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 2/104 (1.9%) | 2 | 0/48 (0%) | 0 |
Pneumonia bacterial | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Pneumonia pneumococcal | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Urinary tract infection | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||
Brain contusion | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Compression fracture | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Fall | 1/102 (1%) | 3 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Femur fracture | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Fracture | 0/102 (0%) | 0 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Gastroenteritis radiation | 0/102 (0%) | 0 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Heat illness | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Radius fracture | 1/102 (1%) | 2 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Spinal compression fracture | 2/102 (2%) | 2 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Subdural haematoma | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Tibia fracture | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Investigations | ||||||||
Alanine aminotransferase increased | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Aspartate aminotransferase increased | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Eastern Cooperative Oncology Group performance status worsened | 0/102 (0%) | 0 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Platelet count decreased | 0/102 (0%) | 0 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||
Muscular weakness | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Neck pain | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Osteoarthritis | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Rhabdomyolysis | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
Adenoma benign | 0/102 (0%) | 0 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Benign duodenal neoplasm | 0/102 (0%) | 0 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Cancer pain | 1/102 (1%) | 1 | 2/85 (2.4%) | 2 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Colon cancer | 1/102 (1%) | 1 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Gastric cancer | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Lung neoplasm malignant | 0/102 (0%) | 0 | 2/85 (2.4%) | 2 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Malignant neoplasm papilla of Vater | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Pancreatic carcinoma | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Prostate cancer | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Nervous system disorders | ||||||||
Altered state of consciousness | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Carotid artery stenosis | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Cerebellar haemorrhage | 0/102 (0%) | 0 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Cerebral haematoma | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Cerebral infarction | 3/102 (2.9%) | 3 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Embolic stroke | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Loss of consciousness | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 1/48 (2.1%) | 1 |
Monoplegia | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Nervous system disorder | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Subarachnoid haemorrhage | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Psychiatric disorders | ||||||||
Delirium | 0/102 (0%) | 0 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 1/48 (2.1%) | 1 |
Mental fatigue | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Renal and urinary disorders | ||||||||
Acute kidney injury | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 1/48 (2.1%) | 1 |
Chronic kidney disease | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Nephrolithiasis | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Postrenal failure | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Urinary bladder haemorrhage | 0/102 (0%) | 0 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Urinary retention | 0/102 (0%) | 0 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 1/48 (2.1%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||||||||
Hypoxia | 0/102 (0%) | 0 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Pneumonia aspiration | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Respiratory failure | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 1/48 (2.1%) | 1 |
Surgical and medical procedures | ||||||||
Aortic stent insertion | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Cataract operation | 0/102 (0%) | 0 | 1/85 (1.2%) | 1 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Inguinal hernia repair | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Large intestinal polypectomy | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 1/104 (1%) | 1 | 0/48 (0%) | 0 |
Ureteric calculus removal | 0/102 (0%) | 0 | 0/85 (0%) | 0 | 0/104 (0%) | 0 | 1/48 (2.1%) | 2 |
Vascular disorders | ||||||||
Aortic aneurysm | 0/102 (0%) | 0 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Aortic dissection | 0/102 (0%) | 0 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 0/48 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
Enzalutamide 160mg 1st Line AAT | Enzalutamide 160mg 2nd Line AAT | Flutamide 375mg 1st Line AAT | Flutamide 375mg 2nd Line AAT | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 79/102 (77.5%) | 56/85 (65.9%) | 65/104 (62.5%) | 22/48 (45.8%) | ||||
Blood and lymphatic system disorders | ||||||||
Anaemia | 3/102 (2.9%) | 3 | 1/85 (1.2%) | 1 | 2/104 (1.9%) | 2 | 4/48 (8.3%) | 4 |
Gastrointestinal disorders | ||||||||
Constipation | 14/102 (13.7%) | 16 | 2/85 (2.4%) | 2 | 3/104 (2.9%) | 3 | 0/48 (0%) | 0 |
Dental caries | 1/102 (1%) | 1 | 5/85 (5.9%) | 5 | 7/104 (6.7%) | 7 | 1/48 (2.1%) | 1 |
Diarrhoea | 7/102 (6.9%) | 7 | 2/85 (2.4%) | 3 | 12/104 (11.5%) | 14 | 6/48 (12.5%) | 6 |
Nausea | 7/102 (6.9%) | 8 | 6/85 (7.1%) | 7 | 5/104 (4.8%) | 5 | 2/48 (4.2%) | 2 |
General disorders | ||||||||
Fatigue | 15/102 (14.7%) | 17 | 8/85 (9.4%) | 10 | 3/104 (2.9%) | 3 | 0/48 (0%) | 0 |
Malaise | 15/102 (14.7%) | 16 | 17/85 (20%) | 19 | 4/104 (3.8%) | 4 | 2/48 (4.2%) | 2 |
Hepatobiliary disorders | ||||||||
Hepatic function abnormal | 2/102 (2%) | 2 | 2/85 (2.4%) | 2 | 9/104 (8.7%) | 10 | 2/48 (4.2%) | 2 |
Infections and infestations | ||||||||
Influenza | 7/102 (6.9%) | 7 | 1/85 (1.2%) | 1 | 2/104 (1.9%) | 2 | 0/48 (0%) | 0 |
Nasopharyngitis | 23/102 (22.5%) | 36 | 12/85 (14.1%) | 17 | 17/104 (16.3%) | 33 | 2/48 (4.2%) | 2 |
Injury, poisoning and procedural complications | ||||||||
Fall | 18/102 (17.6%) | 21 | 10/85 (11.8%) | 10 | 4/104 (3.8%) | 4 | 1/48 (2.1%) | 1 |
Spinal compression fracture | 6/102 (5.9%) | 6 | 1/85 (1.2%) | 1 | 0/104 (0%) | 0 | 1/48 (2.1%) | 1 |
Investigations | ||||||||
Alanine aminotransferase increased | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 7/104 (6.7%) | 8 | 1/48 (2.1%) | 1 |
Aspartate aminotransferase increased | 1/102 (1%) | 1 | 0/85 (0%) | 0 | 6/104 (5.8%) | 7 | 2/48 (4.2%) | 2 |
Metabolism and nutrition disorders | ||||||||
Decreased appetite | 11/102 (10.8%) | 11 | 8/85 (9.4%) | 9 | 4/104 (3.8%) | 5 | 2/48 (4.2%) | 2 |
Musculoskeletal and connective tissue disorders | ||||||||
Back pain | 15/102 (14.7%) | 16 | 4/85 (4.7%) | 4 | 6/104 (5.8%) | 6 | 1/48 (2.1%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
Cancer pain | 5/102 (4.9%) | 5 | 4/85 (4.7%) | 4 | 4/104 (3.8%) | 4 | 4/48 (8.3%) | 4 |
Nervous system disorders | ||||||||
Dizziness | 6/102 (5.9%) | 6 | 5/85 (5.9%) | 5 | 3/104 (2.9%) | 3 | 0/48 (0%) | 0 |
Renal and urinary disorders | ||||||||
Haematuria | 6/102 (5.9%) | 6 | 2/85 (2.4%) | 2 | 2/104 (1.9%) | 2 | 0/48 (0%) | 0 |
Vascular disorders | ||||||||
Hot flush | 4/102 (3.9%) | 4 | 1/85 (1.2%) | 1 | 6/104 (5.8%) | 6 | 0/48 (0%) | 0 |
Hypertension | 13/102 (12.7%) | 15 | 5/85 (5.9%) | 6 | 2/104 (1.9%) | 2 | 0/48 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
Name/Title | Clinical Trial Disclosure |
---|---|
Organization | Astellas Pharma Inc. |
Phone | +81 3-3244-6500 Japanese only |
astellas.resultsdisclosure@astellas.com |
- 9785-MA-3051