Trial Outcomes & Findings for Enzalutamide + External Beam Rt For Prostate (NCT NCT02028988)

NCT ID: NCT02028988

Last Updated: 2023-05-06

Results Overview

Percentage of participants with PSA level of less than or equal to 0.2 ng/ml at the end of six cycles of enzalutamide and EBRT treatment. Post-treatment PSA nadir level has been shown to be a validated intermediate cancer endpoint in similar settings. The chosen cut-off of 0.2 ng/ml was informed by D'Amico et al Lancet Oncology 2012. PSA levels determined through established methods (blood draw and serum analysis).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 64 participants
• Primary outcome timeframe: End of treatment, up to 27 weeks.
• Results posted on: 2023-05-06

Participant Flow

Enrollment from February 2014 to February 2017

Participant milestones

Measure	Enzalutamide With External Beam Radiation Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Overall Study STARTED	64
Overall Study Evaluable if Treatment Completed	62
Overall Study COMPLETED	62
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	Enzalutamide With External Beam Radiation Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Overall Study Withdrawal by Subject	2

Baseline Characteristics

Enzalutamide + External Beam Rt For Prostate

Baseline characteristics by cohort

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Age, Continuous	70 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	64 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants
Race (NIH/OMB) White	50 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants
M Stage MX	9 Participants n=5 Participants
M Stage M0	50 Participants n=5 Participants
M Stage M1	0 Participants n=5 Participants
M Stage Unknown	5 Participants n=5 Participants
N Stage NX	12 Participants n=5 Participants
N Stage N0	50 Participants n=5 Participants
N Stage N1	0 Participants n=5 Participants
N Stage Unknown	2 Participants n=5 Participants
T Stage T1a	0 Participants n=5 Participants
T Stage T1b	0 Participants n=5 Participants
T Stage T1c	43 Participants n=5 Participants
T Stage T2a	18 Participants n=5 Participants
T Stage T2b	1 Participants n=5 Participants
T Stage T2c	2 Participants n=5 Participants
T Stage T3	0 Participants n=5 Participants
Gleason Score 6	2 Participants n=5 Participants
Gleason Score 7	62 Participants n=5 Participants
Primary Gleason Score 3	38 Participants n=5 Participants
Primary Gleason Score 4	26 Participants n=5 Participants
Baseline Prostate Specific Antigen (PSA)	7.72 ng/mL n=5 Participants
Risk Stratification Favorable	10 Participants n=5 Participants
Risk Stratification Unfavorable	54 Participants n=5 Participants

PRIMARY outcome

Timeframe: End of treatment, up to 27 weeks.

Population: Participants who completed treatment are included in this measure.

Percentage of participants with PSA level of less than or equal to 0.2 ng/ml at the end of six cycles of enzalutamide and EBRT treatment. Post-treatment PSA nadir level has been shown to be a validated intermediate cancer endpoint in similar settings. The chosen cut-off of 0.2 ng/ml was informed by D'Amico et al Lancet Oncology 2012. PSA levels determined through established methods (blood draw and serum analysis).

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=62 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Percentage of Participants With PSA at or Below 0.2 ng/ml <=0.2 ng/ml	79 percentage of participants Interval 69.0 to 89.0
Percentage of Participants With PSA at or Below 0.2 ng/ml >0.2 ng/ml	21 percentage of participants Interval 11.0 to 31.0

SECONDARY outcome

Timeframe: Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Median DHEA-S, collected and assessed using established methods. Reference range is 28-640 ug/dL for adult males.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Median DHEA-S Cycle 1	98 ug/dL Interval 1.0 to 305.0
Median DHEA-S Cycle 5	141 ug/dL Interval 16.0 to 580.0
Median DHEA-S End of treatment	135 ug/dL Interval 1.0 to 545.0

SECONDARY outcome

Timeframe: Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Median androstenedione, collected and assessed using established methods. Reference range is 40-150 ng/dL for adult males.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Median Androstenedione Cycle 1	56.5 ng/dL Interval 21.0 to 176.0
Median Androstenedione Cycle 5	77.5 ng/dL Interval 18.0 to 192.0
Median Androstenedione End of treatment	76.5 ng/dL Interval 57.0 to 215.0

SECONDARY outcome

Timeframe: Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Median testosterone, collected and assessed using established methods. Reference range is 300-1050 ng/dL for adult males.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Median Testosterone Cycle 1	349.5 ng/dL Interval 193.0 to 927.0
Median Testosterone Cycle 5	760 ng/dL Interval 168.0 to 2330.0
Median Testosterone End of treatment	730.5 ng/dL Interval 193.0 to 2760.0

SECONDARY outcome

Timeframe: Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Median free testosterone, collected and assessed using established methods. Reference range is 350-1200 ng/dL for adult males.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Median Free Testosterone Cycle 1	66 pg/mL Interval 10.0 to 150.0
Median Free Testosterone Cycle 5	100 pg/mL Interval 24.0 to 330.0
Median Free Testosterone End of treatment	86 pg/mL Interval 10.0 to 340.0

SECONDARY outcome

Timeframe: Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Median estrone, collected and assessed using established methods. Reference range is 12-72 pg/mL for adult males.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Median Estrone Cycle 1	37 pg/mL Interval 18.0 to 72.0
Median Estrone Cycle 5	40 pg/mL Interval 13.0 to 320.0
Median Estrone End of treatment	39 pg/mL Interval 11.0 to 71.0

SECONDARY outcome

Timeframe: Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Median estradiol, collected and assessed using established methods. The reference range is 13-42 pg/mL for adult males.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Median Estradiol Cycle 1	22.5 pg/mL Interval 5.0 to 58.0
Median Estradiol Cycle 5	45 pg/mL Interval 13.0 to 330.0
Median Estradiol End of treatment	45 pg/mL Interval 10.0 to 100.0

SECONDARY outcome

Timeframe: At baseline and end of treatment, up to 27 weeks

Population: The analysis population is comprised of all patients who completed treatment with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Median bicep fat fold measurement taken at baseline and end of treatment.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=62 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Median Bicep Fat Fold Measurement Baseline	14 mm Interval 2.4 to 118.0
Median Bicep Fat Fold Measurement End of treatment	18 mm Interval 1.2 to 42.0

SECONDARY outcome

Timeframe: At baseline and end of treatment, up to 27 weeks

Population: The analysis population is comprised of all patients who completed treatment with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Median tricep fat fold measurement taken at baseline and end of treatment.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=62 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Median Tricep Fat Fold Measurement Baseline	20 mm Interval 2.8 to 39.0
Median Tricep Fat Fold Measurement End of treatment	24 mm Interval 1.2 to 42.0

SECONDARY outcome

Timeframe: At baseline and end of treatment, up to 27 weeks

Population: The analysis population is comprised of all patients who completed treatment with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Median shoulder blade fat fold measurement taken at baseline and end of treatment.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=62 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Median Shoulder Blade Fat Fold Measurement Baseline	20 mm Interval 0.0 to 56.0
Median Shoulder Blade Fat Fold Measurement End of treatment	22 mm Interval 1.2 to 50.0

SECONDARY outcome

Timeframe: At baseline and end of treatment, up to 27 weeks

Population: The analysis population is comprised of all patients who completed treatment with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Median waist fat fold measurement taken at baseline and end of treatment.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=62 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Median Waist Fat Fold Measurement Baseline	28 mm Interval 10.0 to 58.0
Median Waist Fat Fold Measurement End of treatment	28 mm Interval 1.2 to 134.0

SECONDARY outcome

Timeframe: At baseline and end of treatment, up to 27 weeks

Population: The analysis population is comprised of all patients who completed treatment with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Median waist circumference taken at baseline and end of treatment.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=62 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Median Waist Circumference Baseline	104.6 mm Interval 36.0 to 150.0
Median Waist Circumference End of treatment	104.6 mm Interval 12.5 to 134.6

SECONDARY outcome

Timeframe: At baseline and end of treatment, up to 27 weeks

Population: The analysis population is comprised of all patients who completed treatment with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Median weight taken at baseline and end of treatment.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=62 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Median Weight Baseline	87.35 kg Interval 64.1 to 138.2
Median Weight End of treatment	88.26 kg Interval 61.61 to 142.6

SECONDARY outcome

Timeframe: Measured at cycles 1, 3, and 5.

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Sleep quality measure of the Pittsburgh Sleep Quality Index (PSQI) is scored from 0-3 [0=Very bad, 1=Fairly bad, 2=Fairly good, 3=Very good]. The higher the score, the better the sleep quality.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Number of Participants With a Sleep Quality Score of 0 or 1 Cycle 1	54 Participants
Number of Participants With a Sleep Quality Score of 0 or 1 Cycle 3	43 Participants
Number of Participants With a Sleep Quality Score of 0 or 1 Cycle 5	45 Participants

SECONDARY outcome

Timeframe: Measured at cycles 1, 3, and 5.

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Urinary incontinence evaluated using the Expanded-Prostate Index Composite - 26 (EPIC 26) EPIC-26 evaluates patient's urinary incontinence (4 items). The 4 items are reported on a scale of 0 - 100. A higher score indicates better urinary function.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Urinary Incontinence Median Score Cycle 1	100 score Interval 52.0 to 100.0
Urinary Incontinence Median Score Cycle 3	100 score Interval 43.75 to 100.0
Urinary Incontinence Median Score Cycle 5	84.38 score Interval 20.75 to 100.0

SECONDARY outcome

Timeframe: Measured at cycles 1, 3, and 5.

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Urinary irritation evaluated using the Expanded-Prostate Index Composite - 26 (EPIC 26). EPIC-26 evaluates urinary irritation/obstruction (4 items). The final score from the 4 items is reported on a scale of 0 - 100. A higher score indicates better urinary function.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Urinary Irritation Median Score Cycle 1	87.50 score Interval 43.75 to 93.75
Urinary Irritation Median Score Cycle 3	81.25 score Interval 62.5 to 93.75
Urinary Irritation Median Score Cycle 5	62.5 score Interval 12.5 to 93.75

SECONDARY outcome

Timeframe: Measured at cycles 1, 3, and 5.

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Bowel function measure through the Expanded-Prostate Index Composite - 26 (EPIC 26). EPIC-26 evaluates patient's bowel (6 items). The 6 items are reported on a scale of 0 - 100. A higher score indicates better urinary function.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Bowel Function Median Score Cycle 1	100 score Interval 50.0 to 100.0
Bowel Function Median Score Cycle 3	97.92 score Interval 20.83 to 100.0
Bowel Function Median Score Cycle 5	89.58 score Interval 45.83 to 100.0

SECONDARY outcome

Timeframe: Measured at cycles 1, 3, and 5.

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Sexual function measure through The Expanded-Prostate Index Composite - 26 (EPIC 26). EPIC-26 evaluates patient's sexual function (5 items). The 5 items are reported on a scale of 0 - 100.A higher score indicates better urinary function.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Sexual Function Median Score Cycle 1	62.5 score Interval 0.0 to 100.0
Sexual Function Median Score Cycle 3	32 score Interval 0.0 to 100.0
Sexual Function Median Score Cycle 5	19.42 score Interval 0.0 to 100.0

SECONDARY outcome

Timeframe: Measured at cycles 1, 3, and 5.

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Hormone function evaluated by the Expanded-Prostate Index Composite - 26 (EPIC 26). EPIC-26 evaluates patient's hormonal function (5 items). The 5 items are reported on a scale of 0 - 100. A higher score indicates better urinary function.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Hormone Function Median Score Cycle 1	97.50 score Interval 50.0 to 100.0
Hormone Function Median Score Cycle 3	90 score Interval 35.0 to 100.0
Hormone Function Median Score Cycle 5	75 score Interval 25.0 to 100.0

SECONDARY outcome

Timeframe: Cycles 1, 3, and 5

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Feeling fatigue measure of the Patient-Reported Outcome Measurement Information System (PROMIS)-Fatigue Short Form is scored from 0-4 [0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much]. The higher the score, the more fatigued the patient is.

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Number of Participants With a Fatigue Score of 3 or 4 Cycle 1	2 Participants
Number of Participants With a Fatigue Score of 3 or 4 Cycle 3	13 Participants
Number of Participants With a Fatigue Score of 3 or 4 Cycle 5	13 Participants

SECONDARY outcome

Timeframe: Measured at baseline, end of treatment, and at 3 month follow-up, up to 40 weeks

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Median Collagen Type 1 C-Telopeptide is a biomarker for bone metabolism measured and analyzed using established methods. Reference range for adult males is 60-1200 pg/mL

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Median Collagen Type 1 C-Telopeptide Baseline	295.5 pg/mL Interval 208.0 to 379.0
Median Collagen Type 1 C-Telopeptide Off-Treatment	397 pg/mL Interval 310.0 to 541.0
Median Collagen Type 1 C-Telopeptide 3 Month Follow-up	314 pg/mL Interval 229.0 to 407.0

SECONDARY outcome

Timeframe: Measured at baseline, end of treatment, and at 3 month follow-up, up to 40 weeks

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Median Bone-Specific Alkaline Phosphatase is a biomarker for bone metabolism measured and analyzed using established methods. Reference range for adult males is 7.5-69.8 ug/L

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Median Bone-Specific Alkaline Phosphatase Baseline	11.5 ug/L Interval 9.8 to 14.0
Median Bone-Specific Alkaline Phosphatase Off-Treatment	12 ug/L Interval 10.1 to 13.1
Median Bone-Specific Alkaline Phosphatase 3 Month Follow-up	12.6 ug/L Interval 11.0 to 15.3

SECONDARY outcome

Timeframe: Measured at baseline, end of treatment, and at 3 month follow-up, up to 40 weeks

Population: The analysis population is comprised of all enrolled patients with evaluable data for this endpoint at each respective timepoint. As treatment went on, some patients dropped out and/or missed appointments and, as such, data was not collected on these patients.

Median Procollagen Type II Intact N Terminal Propeptide is a biomarker for bone metabolism measured and analyzed using established methods. Reference range for adult males is 22-87 ug/L

Outcome measures

Measure	Enzalutamide With External Beam Radiation n=64 Participants Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Median Procollagen Type II Intact N Terminal Propeptide Baseline	12.8 ug/L Interval 10.0 to 17.0
Median Procollagen Type II Intact N Terminal Propeptide Off-Treatment	13.5 ug/L Interval 11.0 to 17.0
Median Procollagen Type II Intact N Terminal Propeptide 3 Month Follow-up	13.4 ug/L Interval 11.2 to 16.6

Adverse Events

Enzalutamide With External Beam Radiation

Serious events: 0 serious events

Other events: 64 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Enzalutamide With External Beam Radiation n=64 participants at risk Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT Enzalutamide External Beam Radiation
Blood and lymphatic system disorders Anemia	17.2% 11/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Blood and lymphatic system disorders Leukocytosis	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Cardiac disorders Atrial fibrillation	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Cardiac disorders Atrioventricular block first degree	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Cardiac disorders Chest pain - cardiac	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Cardiac disorders Palpitations	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Cardiac disorders Sinus bradycardia	17.2% 11/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Cardiac disorders Cardiac disorders - Other, specify	4.7% 3/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Ear and labyrinth disorders Hearing impaired	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Ear and labyrinth disorders Tinnitus	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Eye disorders Glaucoma	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Eye disorders Eye disorders - Other, specify	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Abdominal pain	6.2% 4/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Bloating	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Cheilitis	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Constipation	18.8% 12/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Diarrhea	28.1% 18/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Dry mouth	4.7% 3/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Dyspepsia	7.8% 5/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Fecal incontinence	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Flatulence	9.4% 6/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Gastroesophageal reflux disease	4.7% 3/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Hemorrhoids	6.2% 4/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Nausea	14.1% 9/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Rectal hemorrhage	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Rectal mucositis	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Rectal pain	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Vomiting	4.7% 3/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	4.7% 3/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders Chills	4.7% 3/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders Edema limbs	9.4% 6/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders Fatigue	79.7% 51/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders Fever	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders Irritability	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders Non-cardiac chest pain	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders Pain	4.7% 3/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Infections and infestations Abdominal infection	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Infections and infestations Prostate infection	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Infections and infestations Sepsis	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Infections and infestations Sinusitis	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Infections and infestations Skin infection	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Infections and infestations Tooth infection	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Infections and infestations Upper respiratory infection	4.7% 3/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Infections and infestations Urinary tract infection	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Injury, poisoning and procedural complications Bruising	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Injury, poisoning and procedural complications Dermatitis radiation	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Alanine aminotransferase increased	7.8% 5/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Aspartate aminotransferase increased	12.5% 8/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Blood bilirubin increased	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Creatinine increased	9.4% 6/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Ejection fraction decreased	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Lymphocyte count decreased	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Neutrophil count decreased	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Platelet count decreased	15.6% 10/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Weight gain	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Weight loss	9.4% 6/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations White blood cell decreased	7.8% 5/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Investigations - Other, specify	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Anorexia	10.9% 7/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Dehydration	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Hypercalcemia	4.7% 3/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Hyperglycemia	45.3% 29/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Hyperkalemia	4.7% 3/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Hypoalbuminemia	6.2% 4/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Hypocalcemia	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Hypoglycemia	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Hypokalemia	7.8% 5/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Hyponatremia	12.5% 8/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Arthralgia	10.9% 7/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Back pain	20.3% 13/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Buttock pain	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	4.7% 3/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Myalgia	7.8% 5/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Pain in extremity	7.8% 5/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Concentration impairment	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Dizziness	14.1% 9/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Dysgeusia	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Headache	7.8% 5/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Lethargy	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Memory impairment	4.7% 3/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Paresthesia	6.2% 4/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Peripheral sensory neuropathy	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Sinus pain	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Psychiatric disorders Agitation	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Psychiatric disorders Anxiety	7.8% 5/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Psychiatric disorders Depression	9.4% 6/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Psychiatric disorders Insomnia	12.5% 8/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Psychiatric disorders Libido decreased	29.7% 19/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Psychiatric disorders Restlessness	4.7% 3/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Renal and urinary disorders Acute kidney injury	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Renal and urinary disorders Cystitis noninfective	4.7% 3/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Renal and urinary disorders Hematuria	7.8% 5/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Renal and urinary disorders Urinary frequency	71.9% 46/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Renal and urinary disorders Urinary incontinence	7.8% 5/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Renal and urinary disorders Urinary retention	9.4% 6/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Renal and urinary disorders Urinary tract pain	20.3% 13/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Renal and urinary disorders Urinary urgency	20.3% 13/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Renal and urinary disorders Renal and urinary disorders - Other, specify	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Reproductive system and breast disorders Breast pain	39.1% 25/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Reproductive system and breast disorders Ejaculation disorder	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Reproductive system and breast disorders Erectile dysfunction	34.4% 22/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Reproductive system and breast disorders Gynecomastia	53.1% 34/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Reproductive system and breast disorders Pelvic pain	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Reproductive system and breast disorders Testicular pain	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Cough	4.7% 3/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Dyspnea	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Nasal congestion	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Sleep apnea	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Sore throat	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Tracheal fistula	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Voice alteration	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Erythema multiforme	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Pruritus	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Rash acneiform	6.2% 4/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Rash maculo-papular	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Skin induration	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Vascular disorders Flushing	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Vascular disorders Hot flashes	20.3% 13/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Vascular disorders Hypertension	62.5% 40/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Vascular disorders Hypotension	3.1% 2/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Vascular disorders Phlebitis	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Vascular disorders Vascular disorders - Other, specify	1.6% 1/64 • Evaluated while on treatment and up to the 3 month follow up visit, up to 40 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.

Additional Information

Glenn Bubley MD

Dana-Farber Cancer Institute

Phone: 617-735-2062

Email: gbubley@bidmc.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place