Study on Enzalutamide and Flutamide in Patients With Cast... | NCT02918968

NCT02918968

Status Module

Sponsor/Collaborators Module

Name	Class
Pfizer	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Enzalutamide 160 mg 1st line AAT/Flutamide 375 mg 2nd line AAT	Experimental	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 Drug: Flutamide Other: Androgen deprivation therapy
Flutamide 375 mg 1st line AAT/Enzaltumide 160 mg 2nd line AAT	Experimental	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 Drug: Flutamide Other: Androgen deprivation therapy

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Enzalutamide	Drug	Oral Capsule	Enzalutamide 160 mg 1st line AAT/Flutamide 375 mg 2nd line AAT Flutamide 375 mg 1st line AAT/Enzaltumide 160 mg 2nd line AAT

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	From date of randomization to the date of PSA progression in the 1st line AAT period (Up to 38 months)

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Medical Director	Astellas Pharma Inc	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Site JP00024		Nagoya	Aichi-ken		Japan
Site JP00025

References Module

Label	URL
Link to results on the Astellas Clinical Study Results website.	View source
Related Info	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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 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).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 3, 2016	May 18, 2021

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Intent-to-Treat (ITT) population was defined as all participants randomized in this study.

Arm/Group Information

ID	Title	Description
BG000	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).
BG001	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).
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00021.39(12.16 to NA)Upper limit of confidence interval was not estimable since the upper confidence limits for the survivor function lay above 0.5. OG0015.78(4.67 to 8.54)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		<0.001	P-value is based on a log-rank test stratified disease stages (M0/N0, M0/N1, or M1).	Hazard Ratio (HR)	0.42			2-Sided	95	0.29	0.61			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.		Superiority	The significance level was 0.05 (two-sided).

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.

ITT population

Posted

Median

95% Confidence Interval

Months

From date of randomization to the date of PSA progression in 2nd line AAT (Up to 38 months)

ID	Title	Description
OG000	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).
OG001

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).

ITT population with participants in each disease stage.

Posted

Number

95% Confidence Interval

Percentage of participants

Baseline and at least 3 weeks after, the lowest PSA decreased by at least 50% or 90% from baseline (Up to 38 months)

ID	Title	Description
OG000	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).

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.

ITT population with participants in each disease stage.

Posted

Number

95% Confidence Interval

Percentage of participants

Baseline and week 13

ID	Title	Description
OG000	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).
OG001	Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT

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.

ITT population with participants in each disease stage.

Posted

Median

95% Confidence Interval

Months

From date of randomization to the day when the decrease of PSA from baseline by 50% is first identified (Up to 38 months)

ID	Title	Description
OG000	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).
OG001	Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT

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.

ITT population with participants in each disease stage.

Posted

Median

95% Confidence Interval

Months

From date of randomization to discontinuation of 1st line AAT (Up to 38 months)

ID	Title	Description
OG000	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).
OG001	Flutamide 375 mg 1st Line AAT/Enzaltumide 160 mg 2nd Line AAT

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.

ITT population

Posted

Median

95% Confidence Interval

Months

From date of randomization to discontinuation of 2nd line AAT (Up to 38 months)

ID	Title	Description
OG000	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).
OG001	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).

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.

ITT population with M1 diseases stage participants. No data reported for M0/N0 and M0/N1 as there are zero participants with event.

Posted

Median

95% Confidence Interval

Months

From date of randomization to the time when radiographic disease progression is observed or death of any cause (up to 38 months)

ID	Title	Description
OG000	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).
OG001

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Enzalutamide 160mg 1st Line AAT	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).	1	102	29	102	79	102
EG001	Enzalutamide 160mg 2nd Line AAT	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).	1	85	18	85	56	85
EG002	Flutamide 375mg 1st Line AAT	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).	0	104	15	104	65	104
EG003	Flutamide 375mg 2nd Line AAT	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).	0	48	4	48	22	48

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG0030 events0 affected48 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0011 events1 affected85 at risk EG0021 events1 affected104 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Cardiac failure acute	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Coronary artery stenosis	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Cataract	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Diverticulum intestinal	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Ileus paralytic	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Inguinal hernia	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Large intestine polyp	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0012 events2 affected85 at risk EG0020 events0 affected104 at risk EG003
Pyrexia	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0012 events2 affected85 at risk EG0021 events1 affected104 at risk EG003
Liver disorder	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Appendicitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Enterocolitis bacterial	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Periodontitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0022 events1 affected104 at risk EG003
Pneumonia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0022 events2 affected104 at risk EG003
Pneumonia bacterial	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Pneumonia pneumococcal	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Brain contusion	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Compression fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0003 events1 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Gastroenteritis radiation	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Heat illness	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Radius fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Eastern Cooperative Oncology Group performance status worsened	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Platelet count decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Adenoma benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Benign duodenal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0012 events2 affected85 at risk EG0020 events0 affected104 at risk EG003
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0012 events2 affected85 at risk EG0020 events0 affected104 at risk EG003
Malignant neoplasm papilla of Vater	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Altered state of consciousness	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Carotid artery stenosis	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Cerebellar haemorrhage	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Cerebral haematoma	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Cerebral infarction	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0003 events3 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Embolic stroke	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Loss of consciousness	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Monoplegia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Nervous system disorder	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Subarachnoid haemorrhage	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Delirium	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Mental fatigue	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Chronic kidney disease	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Postrenal failure	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Urinary bladder haemorrhage	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Aortic stent insertion	Surgical and medical procedures	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Cataract operation	Surgical and medical procedures	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected85 at risk EG0021 events1 affected104 at risk EG003
Inguinal hernia repair	Surgical and medical procedures	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Large intestinal polypectomy	Surgical and medical procedures	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0021 events1 affected104 at risk EG003
Ureteric calculus removal	Surgical and medical procedures	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0010 events0 affected85 at risk EG0020 events0 affected104 at risk EG003
Aortic aneurysm	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Aortic dissection	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0003 events3 affected102 at risk EG0011 events1 affected85 at risk EG0022 events2 affected104 at risk EG0034 events4 affected48 at risk
Constipation	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG00016 events14 affected102 at risk EG0012 events2 affected85 at risk EG0023 events3 affected104 at risk EG003
Dental caries	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0015 events5 affected85 at risk EG0027 events7 affected104 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0007 events7 affected102 at risk EG0013 events2 affected85 at risk EG00214 events12 affected104 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0008 events7 affected102 at risk EG0017 events6 affected85 at risk EG0025 events5 affected104 at risk EG003
Fatigue	General disorders	MedDRA 23.0	Systematic Assessment	EG00017 events15 affected102 at risk EG00110 events8 affected85 at risk EG0023 events3 affected104 at risk EG003
Malaise	General disorders	MedDRA 23.0	Systematic Assessment	EG00016 events15 affected102 at risk EG00119 events17 affected85 at risk EG0024 events4 affected104 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected102 at risk EG0012 events2 affected85 at risk EG00210 events9 affected104 at risk EG003
Influenza	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0007 events7 affected102 at risk EG0011 events1 affected85 at risk EG0022 events2 affected104 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG00036 events23 affected102 at risk EG00117 events12 affected85 at risk EG00233 events17 affected104 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG00021 events18 affected102 at risk EG00110 events10 affected85 at risk EG0024 events4 affected104 at risk EG003
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0006 events6 affected102 at risk EG0011 events1 affected85 at risk EG0020 events0 affected104 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0028 events7 affected104 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected85 at risk EG0027 events6 affected104 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG00011 events11 affected102 at risk EG0019 events8 affected85 at risk EG0025 events4 affected104 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG00016 events15 affected102 at risk EG0014 events4 affected85 at risk EG0026 events6 affected104 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0005 events5 affected102 at risk EG0014 events4 affected85 at risk EG0024 events4 affected104 at risk EG003
Dizziness	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0006 events6 affected102 at risk EG0015 events5 affected85 at risk EG0023 events3 affected104 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0006 events6 affected102 at risk EG0012 events2 affected85 at risk EG0022 events2 affected104 at risk EG003
Hot flush	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0004 events4 affected102 at risk EG0011 events1 affected85 at risk EG0026 events6 affected104 at risk EG003
Hypertension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG00015 events13 affected102 at risk EG0016 events5 affected85 at risk EG0022 events2 affected104 at risk EG003

ID	Term
D011471	Prostatic Neoplasms

Ancestor Terms

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Term
C540278	enzalutamide
D005485	Flutamide
D000726	Androgen Antagonists

Ancestor Terms

ID	Term
D000813	Anilides
D000577	Amides
D009930	Organic Chemicals
D000814	Aniline Compounds
D000588	Amines
D006727	Hormone Antagonists
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D045505	Physiological Effects of Drugs
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses

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).

Median was not estimable since KM estimate did not reach to 50%. Lower limit of confidence interval was not estimable since the lower confidence limits for the survivor function lay above 0.5. Upper limit of confidence interval was not estimable since the upper confidence limits for the survivor function lay above 0.5.

Upper limit of confidence interval was not estimable since the upper confidence limits for the survivor function lay above 0.5.

OG001NA(29.08 to NA)Median was not estimable since KM estimate did not reach to 50%. Upper limit of confidence interval was not estimable since the upper confidence limits for the survivor function lay above 0.5.