Trial Outcomes & Findings for Hormone Therapy, Radiation Therapy, and Steroid 17alpha-monooxygenase TAK-700 in Treating Patients With High-Risk Prostate Cancer (NCT NCT01546987)

NCT ID: NCT01546987

Last Updated: 2025-10-15

Results Overview

Note, the revised protocol (see Limitations and Caveats) changed this outcome measure from secondary (original protocol) to primary. Biochemical failure will be defined by the Phoenix definition (PSA ≥ 2 ng/ml over the nadir PSA, the presence of local, regional, or distant recurrence, or the initiation of salvage androgen deprivation therapy. Time to failure is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 239 participants
• Primary outcome timeframe: From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.
• Results posted on: 2025-10-15

Participant Flow

Participant milestones

Measure	ADT + RT Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Overall Study STARTED	118	120
Overall Study Eligible	115	116
Overall Study Eligible Participants Who Consented to Quality of Life (QOL) Component	103	94
Overall Study COMPLETED	115	116
Overall Study NOT COMPLETED	3	4

Reasons for withdrawal

Measure	ADT + RT Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Overall Study Protocol Violation	3	4

Baseline Characteristics

Trial was amended midstudy to add this stratification variable, therefore data was not collected on all participants.

Baseline characteristics by cohort

Measure	ADT + RT n=115 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=116 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.	Total n=231 Participants Total of all reporting groups
Study Entry PSA 20.0-150.0 ng/ml	40 Participants n=115 Participants	41 Participants n=116 Participants	81 Participants n=231 Participants
Age, Customized ≤ 49 years	2 Participants n=115 Participants	1 Participants n=116 Participants	3 Participants n=231 Participants
Age, Customized 50 - 59 years	16 Participants n=115 Participants	22 Participants n=116 Participants	38 Participants n=231 Participants
Age, Customized 60 - 69 years	44 Participants n=115 Participants	41 Participants n=116 Participants	85 Participants n=231 Participants
Age, Customized ≥ 70 years	53 Participants n=115 Participants	52 Participants n=116 Participants	105 Participants n=231 Participants
Sex: Female, Male Female	0 Participants n=115 Participants	0 Participants n=116 Participants	0 Participants n=231 Participants
Sex: Female, Male Male	115 Participants n=115 Participants	116 Participants n=116 Participants	231 Participants n=231 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=115 Participants	5 Participants n=116 Participants	7 Participants n=231 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	111 Participants n=115 Participants	109 Participants n=116 Participants	220 Participants n=231 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=115 Participants	2 Participants n=116 Participants	4 Participants n=231 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=115 Participants	0 Participants n=116 Participants	1 Participants n=231 Participants
Race (NIH/OMB) Asian	1 Participants n=115 Participants	1 Participants n=116 Participants	2 Participants n=231 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=115 Participants	0 Participants n=116 Participants	0 Participants n=231 Participants
Race (NIH/OMB) Black or African American	14 Participants n=115 Participants	10 Participants n=116 Participants	24 Participants n=231 Participants
Race (NIH/OMB) White	93 Participants n=115 Participants	101 Participants n=116 Participants	194 Participants n=231 Participants
Race (NIH/OMB) More than one race	0 Participants n=115 Participants	0 Participants n=116 Participants	0 Participants n=231 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=115 Participants	4 Participants n=116 Participants	10 Participants n=231 Participants
Zubrod Performance Status 0	99 Participants n=115 Participants	104 Participants n=116 Participants	203 Participants n=231 Participants
Zubrod Performance Status 1	16 Participants n=115 Participants	12 Participants n=116 Participants	28 Participants n=231 Participants
Gleason Score 7	16 Participants n=115 Participants	18 Participants n=116 Participants	34 Participants n=231 Participants
Gleason Score 8	37 Participants n=115 Participants	30 Participants n=116 Participants	67 Participants n=231 Participants
Gleason Score ≥9	62 Participants n=115 Participants	68 Participants n=116 Participants	130 Participants n=231 Participants
Study Entry PSA < 20.0 ng/ml	75 Participants n=115 Participants	75 Participants n=116 Participants	150 Participants n=231 Participants
T-Stage T1a-T1c	22 Participants n=115 Participants	23 Participants n=116 Participants	45 Participants n=231 Participants
T-Stage T2-T2c	66 Participants n=115 Participants	58 Participants n=116 Participants	124 Participants n=231 Participants
T-Stage T3-T3b	24 Participants n=115 Participants	33 Participants n=116 Participants	57 Participants n=231 Participants
T-Stage T4	3 Participants n=115 Participants	2 Participants n=116 Participants	5 Participants n=231 Participants
Risk Factors Gleason ≥ 9, PSA ≤150, any T-stage	65 Participants n=115 Participants	67 Participants n=116 Participants	132 Participants n=231 Participants
Risk Factors Gleason 8, PSA <20, and ≥T2	23 Participants n=115 Participants	21 Participants n=116 Participants	44 Participants n=231 Participants
Risk Factors Gleason 8, PSA ≥20-150, any T-stage	13 Participants n=115 Participants	10 Participants n=116 Participants	23 Participants n=231 Participants
Risk Factors Gleason 7, PSA ≥20-150, any T-stage	14 Participants n=115 Participants	18 Participants n=116 Participants	32 Participants n=231 Participants
N-Stage N0	115 Participants n=115 Participants	116 Participants n=116 Participants	231 Participants n=231 Participants
M-Stage M0	115 Participants n=115 Participants	116 Participants n=116 Participants	231 Participants n=231 Participants
ADT Started Prior to Registration No	31 Participants n=42 Participants • Trial was amended midstudy to add this stratification variable, therefore data was not collected on all participants.	25 Participants n=45 Participants • Trial was amended midstudy to add this stratification variable, therefore data was not collected on all participants.	56 Participants n=87 Participants • Trial was amended midstudy to add this stratification variable, therefore data was not collected on all participants.
ADT Started Prior to Registration Yes	11 Participants n=42 Participants • Trial was amended midstudy to add this stratification variable, therefore data was not collected on all participants.	20 Participants n=45 Participants • Trial was amended midstudy to add this stratification variable, therefore data was not collected on all participants.	31 Participants n=87 Participants • Trial was amended midstudy to add this stratification variable, therefore data was not collected on all participants.
RT Boost Modality Intensity-modulated radiation therapy (IMRT)	103 Participants n=115 Participants	105 Participants n=116 Participants	208 Participants n=231 Participants
RT Boost Modality Low dose rate (LDR) permanent prostate implant (PPI)	12 Participants n=115 Participants	10 Participants n=116 Participants	22 Participants n=231 Participants
RT Boost Modality High dose rate (HDR) implant	0 Participants n=115 Participants	1 Participants n=116 Participants	1 Participants n=231 Participants

PRIMARY outcome

Timeframe: From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.

Population: Eligible participants

Note, the revised protocol (see Limitations and Caveats) changed this outcome measure from secondary (original protocol) to primary. Biochemical failure will be defined by the Phoenix definition (PSA ≥ 2 ng/ml over the nadir PSA, the presence of local, regional, or distant recurrence, or the initiation of salvage androgen deprivation therapy. Time to failure is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here.

Outcome measures

Measure	ADT + RT n=115 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=116 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Percentage of Participants With Biochemical Failure (Primary Endpoint of Revised Protocol)	17.3 percentage of participants Interval 10.7 to 25.2	12.8 percentage of participants Interval 7.1 to 20.1

SECONDARY outcome

Timeframe: From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.

Population: Eligible participants

Note, the revised protocol (see Limitations and Caveats) changed this outcome measure from primary (original protocol) to secondary. Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. 5-year rates are provided.

Outcome measures

Measure	ADT + RT n=115 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=116 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Percentage of Patients Alive [Overall Survival] (Primary Endpoint of Original Protocol)	89.4 percentage of participants Interval 83.5 to 95.3	88.1 percentage of participants Interval 81.8 to 94.4

SECONDARY outcome

Timeframe: From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.

Population: Eligible participants

Time to grade 3 or higher adverse event (event) is defined as time from randomization to the date of first event, last known follow-up (censored), or death without failure (competing risk). Event rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here.

Outcome measures

Measure	ADT + RT n=115 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=116 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Percentage of Participants With Grade 3 or Higher Adverse Events	34.9 percentage of participants Interval 26.0 to 43.9	58.9 percentage of participants Interval 48.8 to 67.6

SECONDARY outcome

Timeframe: From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates reported.

Population: Eligible participants

Local recurrence (failure) is defined as biopsy proven recurrence within the prostate gland. Time to failure is defined as time from randomization to the date of failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here.

Outcome measures

Measure	ADT + RT n=115 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=116 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Percentage of Participants With Local Progression	2.9 percentage of participants Interval 0.8 to 7.6	0.0 percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.

Population: Eligible participants

Distant metastases (failure) is defined as imaging or biopsy demonstrated evidence for systemic recurrence. Biopsy was not required, however it was encouraged in absence of a rising PSA. Time to failure is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here. Note, the protocol lists this endpoint as regional or distant metastasis, but regional progression data was not collected.

Outcome measures

Measure	ADT + RT n=115 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=116 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Percentage of Participants With Distant Metastases	6.8 percentage of participants Interval 3.0 to 12.7	2.9 percentage of participants Interval 0.8 to 7.7

SECONDARY outcome

Timeframe: From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.

Population: Eligible participants

General clinical treatment failure (GCTF) is defined as: PSA > 25 ng/ml, documented local disease progression, regional or distant metastasis, or initiation of salvage androgen deprivation therapy. Failure time is defined as time from registration to the date of failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here.

Outcome measures

Measure	ADT + RT n=115 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=116 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Percentage of Participants With General Clinical Treatment Failure	12.5 percentage of participants Interval 7.0 to 19.6	6.8 percentage of participants Interval 3.0 to 12.8

SECONDARY outcome

Timeframe: From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.

Population: Eligible participants

Time to prostate cancer death is defined as time from randomization to the date of death due to prostate cancer, last known follow-up (censored), or death due to other causes (competing risk). Failure rates were to be estimated using the cumulative incidence method. If too few events occur for meaningful estimates, then only counts of events will be reported.

Outcome measures

Measure	ADT + RT n=115 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=116 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Percentage of Participants With Death Due to Prostate Cancer	7.7 percentage of participants Interval 3.6 to 13.9	4.9 percentage of participants Interval 1.8 to 10.5

SECONDARY outcome

Timeframe: Baseline, one year

Population: Eligible participants who consented to quality of life component and had baseline and one-year data.

The PROMIS Fatigue short form 8a contains 8 questions, each with 5 responses ranging from 1 to 5, evaluating self-reported fatigue symptoms over the past 7 days. The total score is the sum of all questions which is then converted into a pro-rated T-score with a mean of 50 and standard deviation of 10, with a possible range of 33.1 to 77.8. Higher scores indicate more fatigue. Change is defined as value at one year - value at baseline. Positive change from baseline indicates increased fatigue at one year.

Outcome measures

Measure	ADT + RT n=78 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=73 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Change in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form at One Year	2.78 T-score Standard Deviation 7.21	3.16 T-score Standard Deviation 8.24

SECONDARY outcome

Timeframe: Baseline, one year

Population: Eligible participants with data for any of the four domains.

The EPIC-Short Form is a 26-item, validated self-administered tool to assess disease-specific aspects of prostate cancer and its therapies consisting of five summary domains (bowel, urinary incontinence, urinary irritation/obstruction, sexual, and hormonal function). Responses for each item form a Likert scale which are transformed to a 0-100 scale. A domain score is the average of the transformed domain item scores, ranging from 0-100 with higher scores representing better health-related quality of life (HRQOL). Change at one year is defined as one-year value - baseline value. Positive change at one year indicates improved quality of life.

Outcome measures

Measure	ADT + RT n=102 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=94 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year Bowel domain	-5.45 score on a scale Standard Deviation 9.10	-7.04 score on a scale Standard Deviation 15.50
Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year Urinary domain	-1.67 score on a scale Standard Deviation 13.90	-5.31 score on a scale Standard Deviation 15.46
Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year Sexual domain	-24.18 score on a scale Standard Deviation 27.64	-27.26 score on a scale Standard Deviation 25.98
Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year Hormonal domain	-17.31 score on a scale Standard Deviation 15.36	-17.45 score on a scale Standard Deviation 16.59

SECONDARY outcome

Timeframe: Baseline,12 months, 24 months

Population: Eligible participants with data at any of the timepoints.

Outcome measures

Measure	ADT + RT n=115 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=116 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Serum Testosterone Baseline	355.75 ng/dL Standard Deviation 225.65	357.73 ng/dL Standard Deviation 217.26
Serum Testosterone 12 months	35.68 ng/dL Standard Deviation 68.39	25.22 ng/dL Standard Deviation 67.49
Serum Testosterone 24 months	86.47 ng/dL Standard Deviation 182.40	17.36 ng/dL Standard Deviation 32.71

SECONDARY outcome

Timeframe: Baseline, 12 months, 24 months

Population: Eligible participants with data at any of the timepoints.

Outcome measures

Measure	ADT + RT n=114 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=116 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Fasting Total Cholesterol Baseline	149.71 mg/dL Standard Deviation 68.20	154.20 mg/dL Standard Deviation 71.05
Fasting Total Cholesterol 12 months	160.27 mg/dL Standard Deviation 73.22	154.74 mg/dL Standard Deviation 70.85
Fasting Total Cholesterol 24 months	163.20 mg/dL Standard Deviation 168.63	160.61 mg/dL Standard Deviation 77.55

SECONDARY outcome

Timeframe: Baseline, 12 months, 24 months

Population: Eligible participants with data at any of the timepoints.

Outcome measures

Measure	ADT + RT n=114 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=116 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Serum High-density Lipoprotein (HDL) Baseline	40.91 mg/dL Standard Deviation 20.96	41.32 mg/dL Standard Deviation 20.93
Serum High-density Lipoprotein (HDL) 12 months	44.94 mg/dL Standard Deviation 24.21	44.50 mg/dL Standard Deviation 24.21
Serum High-density Lipoprotein (HDL) 24 months	42.16 mg/dL Standard Deviation 23.77	44.85 mg/dL Standard Deviation 23.36

SECONDARY outcome

Timeframe: Baseline, 12 months, 24 months

Population: Eligible participants with data at any of the timepoints.

Outcome measures

Measure	ADT + RT n=114 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=116 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Serum High-density Lipoprotein (LDL) Baseline	88.78 mg/dL Standard Deviation 45.64	87.85 mg/dL Standard Deviation 47.33
Serum High-density Lipoprotein (LDL) 12 months	86.18 mg/dL Standard Deviation 47.11	83.73 mg/dL Standard Deviation 46.86
Serum High-density Lipoprotein (LDL) 24 months	81.35 mg/dL Standard Deviation 47.73	95.34 mg/dL Standard Deviation 59.22

SECONDARY outcome

Timeframe: Baseline, 12 months, 24 months

Population: Eligible participants with data at any of the timepoints.

Outcome measures

Measure	ADT + RT n=114 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=115 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Hemoglobin A1c Baseline	6.12 g/dL Standard Deviation 1.05	6.01 g/dL Standard Deviation 1.05
Hemoglobin A1c 12 months	6.33 g/dL Standard Deviation 1.18	5.95 g/dL Standard Deviation 0.73
Hemoglobin A1c 24 months	6.30 g/dL Standard Deviation 1.59	6.04 g/dL Standard Deviation 0.76

SECONDARY outcome

Timeframe: Baseline, 12 months, 24 months

Population: Eligible participants with data at any of the timepoints.

Outcome measures

Measure	ADT + RT n=112 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=115 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Fasting Plasma Glucose Baseline	98.99 mg/dL Standard Deviation 51.87	100.52 mg/dL Standard Deviation 45.54
Fasting Plasma Glucose 12 months	102.27 mg/dL Standard Deviation 53.06	117.39 mg/dL Standard Deviation 118.40
Fasting Plasma Glucose 24 months	104.24 mg/dL Standard Deviation 67.43	105.51 mg/dL Standard Deviation 40.53

SECONDARY outcome

Timeframe: Baseline, 12 months, 24 months

Population: This data was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and yearly to five years.

Population: Eligible participants data at baseline and data at any of the post-baseline timepoints.

Body Mass Index (BMI) is a person's weight in kilograms (or pounds) divided by the square of height in meters (or feet). Change from baseline = time point value - baseline value.

Outcome measures

Measure	ADT + RT n=111 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=107 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Change From Baseline in Body Mass Index (BMI) 1 year	0.64 kg/m^2 Standard Deviation 2.19	-0.84 kg/m^2 Standard Deviation 4.28
Change From Baseline in Body Mass Index (BMI) 2 years	0.67 kg/m^2 Standard Deviation 3.76	-0.34 kg/m^2 Standard Deviation 2.55
Change From Baseline in Body Mass Index (BMI) 3 years	0.75 kg/m^2 Standard Deviation 3.90	0.25 kg/m^2 Standard Deviation 2.32
Change From Baseline in Body Mass Index (BMI) 4 years	-0.02 kg/m^2 Standard Deviation 6.95	0.46 kg/m^2 Standard Deviation 2.70
Change From Baseline in Body Mass Index (BMI) 5 years	-0.52 kg/m^2 Standard Deviation 3.01	0.15 kg/m^2 Standard Deviation 2.71

SECONDARY outcome

Timeframe: From registration to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.

Population: Eligible participants who started protocol treatment

Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data

Outcome measures

Measure	ADT + RT n=112 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=115 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Number of Participants by Highest Grade Adverse Event Grade 1	17 Participants	2 Participants
Number of Participants by Highest Grade Adverse Event Grade 2	54 Participants	45 Participants
Number of Participants by Highest Grade Adverse Event Grade 3	31 Participants	55 Participants
Number of Participants by Highest Grade Adverse Event Garde 4	4 Participants	9 Participants
Number of Participants by Highest Grade Adverse Event Grade 5	3 Participants	1 Participants

SECONDARY outcome

Timeframe: From registration to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years.

Population: Eligible participants with testosterone data

Testosterone recovery is defined as testosterone level after treatment greater than 230 ng/dL. Time to testosterone recovery is defined as time from randomization to the date of testosterone recovery, biochemical, local, or distant failure (competing risk), salvage therapy (competing risk), death (competing risk), or last known follow-up (censored). Testosterone recovery rates are estimated using the cumulative incidence method.

Outcome measures

Measure	ADT + RT n=112 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=113 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Testosterone Recovery at 12 and 24 Months 12 months	19.4 percentage of participants Interval 12.5 to 27.3	12.5 percentage of participants Interval 7.0 to 19.6
Testosterone Recovery at 12 and 24 Months 24 months	32.9 percentage of participants Interval 24.1 to 41.9	17.4 percentage of participants Interval 10.8 to 25.4

SECONDARY outcome

Timeframe: From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.

Population: Eligible participants with testosterone data

Testosterone recovery is defined as testosterone level after treatment greater than 230 ng/dL. Testosterone recovery rates are estimated using the Kaplan-Meier method, censoring for biochemical, local, or distant failure, salvage therapy, death, and otherwise alive without event. Testosterone recovery time is defined as time from randomization to testosterone recovery or censoring.

Outcome measures

Measure	ADT + RT n=112 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=113 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Median Testosterone Recovery Time	NA years Interval 4.2 to The median and the upper confidence limit were not reached.	NA years The median, and the lower and upper 95% confidence limits were not reached

SECONDARY outcome

Timeframe: From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.

Population: Eligible participants

Clinical survivorship events are defined as the following newly diagnosed non-fatal cardiovascular events or other clinical endpoints relevant to prostate cancer survivorship:

type 2 diabetes, coronary artery disease, myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis, and osteoporotic fracture.

Outcome measures

Measure	ADT + RT n=115 Participants Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=116 Participants TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Number of Patients With Clinical Survivorship Events Type 2 diabetes	30 Participants	18 Participants
Number of Patients With Clinical Survivorship Events Coronary artery disease	16 Participants	14 Participants
Number of Patients With Clinical Survivorship Events Myocardial infarction	6 Participants	8 Participants
Number of Patients With Clinical Survivorship Events Stroke	5 Participants	6 Participants
Number of Patients With Clinical Survivorship Events Pulmonary embolism	10 Participants	5 Participants
Number of Patients With Clinical Survivorship Events Deep vein thrombosis	8 Participants	7 Participants
Number of Patients With Clinical Survivorship Events Osteoporotic fracture	6 Participants	1 Participants

Adverse Events

ADT + RT

Serious events: 19 serious events

Other events: 108 other events

Deaths: 24 deaths

TAK-700 + ADT + RT

Serious events: 38 serious events

Other events: 112 other events

Deaths: 19 deaths

Serious adverse events

Measure	ADT + RT n=112 participants at risk Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=115 participants at risk TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Blood and lymphatic system disorders Anemia	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Cardiac disorders Acute coronary syndrome	1.8% 2/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Cardiac disorders Aortic valve disease	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	1.7% 2/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Cardiac disorders Atrial fibrillation	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	2.6% 3/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Cardiac disorders Atrial flutter	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Cardiac disorders Cardiac disorders - Other	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Cardiac disorders Chest pain - cardiac	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Cardiac disorders Heart failure	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Cardiac disorders Left ventricular systolic dysfunction	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Cardiac disorders Mitral valve disease	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Cardiac disorders Myocardial infarction	2.7% 3/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	3.5% 4/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Cardiac disorders Sinus bradycardia	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Eye disorders Eye disorders - Other	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Abdominal pain	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Colitis	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Colonic obstruction	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Constipation	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Diarrhea	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Dysphagia	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Nausea	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Rectal fistula	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Vomiting	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
General disorders Death NOS	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
General disorders Fatigue	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	1.7% 2/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
General disorders Irritability	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
General disorders Sudden death NOS	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Hepatobiliary disorders Gallbladder pain	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Infections and infestations Appendicitis	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Infections and infestations Bronchial infection	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Infections and infestations Enterocolitis infectious	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Infections and infestations Lung infection	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Infections and infestations Sepsis	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Infections and infestations Skin infection	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Infections and infestations Urinary tract infection	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Injury, poisoning and procedural complications Hip fracture	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Investigations Aspartate aminotransferase increased	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Investigations Lymphocyte count decreased	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Metabolism and nutrition disorders Anorexia	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	1.7% 2/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Amnesia	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Cognitive disturbance	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Dizziness	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	1.7% 2/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Nervous system disorders - Other	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Paresthesia	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Reversible posterior leukoencephalopathy syndrome	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Seizure	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Stroke	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	2.6% 3/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Syncope	1.8% 2/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Transient ischemic attacks	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Acute kidney injury	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Bladder spasm	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Hematuria	1.8% 2/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Renal calculi	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	2.6% 3/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Urinary frequency	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Urinary retention	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Urinary tract obstruction	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Reproductive system and breast disorders Erectile dysfunction	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Respiratory, thoracic and mediastinal disorders Aspiration	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders -	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Surgical and medical procedures Surgical and medical procedures - Other	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Vascular disorders Hematoma	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Vascular disorders Hot flashes	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Vascular disorders Hypertension	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Vascular disorders Hypotension	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.00% 0/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Vascular disorders Thromboembolic event	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	2.6% 3/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Vascular disorders Vascular disorders - Other	0.00% 0/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	0.87% 1/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.

Other adverse events

Measure	ADT + RT n=112 participants at risk Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.	TAK-700 + ADT + RT n=115 participants at risk TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
Blood and lymphatic system disorders Anemia	17.9% 20/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	20.0% 23/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Abdominal pain	7.1% 8/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	14.8% 17/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Constipation	20.5% 23/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	27.8% 32/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Diarrhea	54.5% 61/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	60.0% 69/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Dyspepsia	1.8% 2/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	5.2% 6/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Fecal incontinence	3.6% 4/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	5.2% 6/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Flatulence	9.8% 11/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	9.6% 11/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Gastroesophageal reflux disease	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	6.1% 7/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Gastrointestinal disorders - Other	16.1% 18/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	20.0% 23/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Hemorrhoids	6.2% 7/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	5.2% 6/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Nausea	8.0% 9/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	33.0% 38/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Proctitis	16.1% 18/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	11.3% 13/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Rectal hemorrhage	15.2% 17/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	11.3% 13/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Gastrointestinal disorders Vomiting	3.6% 4/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	13.9% 16/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
General disorders Edema limbs	8.0% 9/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	14.8% 17/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
General disorders Fatigue	64.3% 72/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	79.1% 91/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
General disorders General disorders and administration site conditio	8.0% 9/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	13.0% 15/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
General disorders Pain	13.4% 15/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	15.7% 18/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Infections and infestations Infections and infestations - Other	6.2% 7/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	3.5% 4/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Infections and infestations Urinary tract infection	6.2% 7/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	9.6% 11/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Injury, poisoning and procedural complications Dermatitis radiation	3.6% 4/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	5.2% 6/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Investigations Alanine aminotransferase increased	8.9% 10/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	21.7% 25/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Investigations Alkaline phosphatase increased	8.0% 9/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	8.7% 10/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Investigations Aspartate aminotransferase increased	8.9% 10/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	20.9% 24/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Investigations Cholesterol high	2.7% 3/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	13.9% 16/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Investigations Creatinine increased	8.9% 10/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	13.9% 16/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Investigations Investigations - Other	7.1% 8/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	12.2% 14/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Investigations Lymphocyte count decreased	9.8% 11/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	8.7% 10/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Investigations Weight gain	8.9% 10/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	6.1% 7/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Investigations Weight loss	8.9% 10/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	24.3% 28/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Investigations White blood cell decreased	4.5% 5/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	11.3% 13/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Metabolism and nutrition disorders Anorexia	8.9% 10/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	23.5% 27/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Metabolism and nutrition disorders Dehydration	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	5.2% 6/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Metabolism and nutrition disorders Hyperglycemia	29.5% 33/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	33.9% 39/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Metabolism and nutrition disorders Hyperkalemia	2.7% 3/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	6.1% 7/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Metabolism and nutrition disorders Hypertriglyceridemia	8.9% 10/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	11.3% 13/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Metabolism and nutrition disorders Hypokalemia	4.5% 5/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	8.7% 10/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Metabolism and nutrition disorders Hypomagnesemia	4.5% 5/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	8.7% 10/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Metabolism and nutrition disorders Hyponatremia	5.4% 6/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	9.6% 11/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other	8.0% 9/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	8.7% 10/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Musculoskeletal and connective tissue disorders Arthralgia	8.9% 10/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	13.0% 15/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Musculoskeletal and connective tissue disorders Arthritis	5.4% 6/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	8.7% 10/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Musculoskeletal and connective tissue disorders Back pain	21.4% 24/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	13.0% 15/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	11.6% 13/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	16.5% 19/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	5.4% 6/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	3.5% 4/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder -	9.8% 11/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	13.0% 15/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Musculoskeletal and connective tissue disorders Myalgia	2.7% 3/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	10.4% 12/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	13.4% 15/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	12.2% 14/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Dizziness	10.7% 12/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	25.2% 29/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Dysgeusia	1.8% 2/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	7.8% 9/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Headache	8.9% 10/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	18.3% 21/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Memory impairment	5.4% 6/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	1.7% 2/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Nervous system disorders - Other	2.7% 3/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	6.1% 7/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Nervous system disorders Peripheral sensory neuropathy	6.2% 7/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	7.0% 8/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Psychiatric disorders Anxiety	6.2% 7/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	12.2% 14/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Psychiatric disorders Depression	11.6% 13/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	17.4% 20/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Psychiatric disorders Insomnia	17.0% 19/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	19.1% 22/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Psychiatric disorders Libido decreased	13.4% 15/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	12.2% 14/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Cystitis noninfective	12.5% 14/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	14.8% 17/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Hematuria	15.2% 17/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	13.0% 15/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Renal and urinary disorders - Other	37.5% 42/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	40.0% 46/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Urinary frequency	66.1% 74/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	72.2% 83/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Urinary incontinence	24.1% 27/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	15.7% 18/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Urinary retention	19.6% 22/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	20.9% 24/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Urinary tract obstruction	6.2% 7/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	7.0% 8/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Urinary tract pain	17.9% 20/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	18.3% 21/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Renal and urinary disorders Urinary urgency	43.8% 49/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	32.2% 37/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Reproductive system and breast disorders Erectile dysfunction	43.8% 49/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	40.9% 47/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Reproductive system and breast disorders Gynecomastia	7.1% 8/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	6.1% 7/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Respiratory, thoracic and mediastinal disorders Cough	6.2% 7/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	12.2% 14/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	9.8% 11/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	21.7% 25/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders -	0.89% 1/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	5.2% 6/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Skin and subcutaneous tissue disorders Alopecia	1.8% 2/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	6.1% 7/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Skin and subcutaneous tissue disorders Dry skin	3.6% 4/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	7.0% 8/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Skin and subcutaneous tissue disorders Pruritus	4.5% 5/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	7.0% 8/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	3.6% 4/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	7.8% 9/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	4.5% 5/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	11.3% 13/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Vascular disorders Hot flashes	74.1% 83/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	77.4% 89/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Vascular disorders Hypertension	16.1% 18/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	32.2% 37/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Vascular disorders Hypotension	1.8% 2/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	5.2% 6/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.
Vascular disorders Vascular disorders - Other	5.4% 6/112 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.	5.2% 6/115 • From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. All-cause mortality was assessed in eligible participants. Adverse events were assessed in eligible participants who started protocol treatment.

Additional Information

Wendy Seiferheld

NRG Oncology

Phone: 215-574-3208

Email: seiferheldw@nrgoncology.org

Results disclosure agreements

• Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
• Publication restrictions are in place

Restriction type: OTHER