Trial Outcomes & Findings for Genetic and Molecular Mechanisms in Assessing Response in Patients With Prostate Cancer Receiving Enzalutamide Therapy (NCT NCT02099864)

NCT ID: NCT02099864

Last Updated: 2024-09-19

Results Overview

The percentage of participants with a \>= 50% decline in PSA values will be reported with 95% exact confidence interval. For each participant, percentage decline in PSA values are calculated as 100% times the difference between PSA values taken at baseline and 12 weeks divided by PSA values at baseline. Percentage of participants determined as 100% times the number of participants with \>= 50% decline divided by overall number of participants.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 36 participants
• Primary outcome timeframe: Baseline to 12 weeks
• Results posted on: 2024-09-19

Participant Flow

Participant milestones

Measure	Treatment (Enzalutamide) Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO
Overall Study STARTED	36
Overall Study COMPLETED	36
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Genetic and Molecular Mechanisms in Assessing Response in Patients With Prostate Cancer Receiving Enzalutamide Therapy

Baseline characteristics by cohort

Measure	Treatment (Enzalutamide) n=36 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants
Age, Categorical >=65 years	29 Participants n=5 Participants
Age, Continuous	71.9 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 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	1 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Region of Enrollment United States	36 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Population: Evaluable patients will include those patients for whom data from genomic studies and IHC tests are available from the pre-treatment biopsy samples and who have completed at least 12 weeks of therapy or who have confirmed disease progression prior to 12 weeks of therapy, and for whom baseline and 12 week PSA data were available. 36 subjects shown in participant flow. 2 subjects were excluded from this PSA analysis: 1 had missing PSA data, 1 had falling PSA in setting of rapid disease progression

The percentage of participants with a >= 50% decline in PSA values will be reported with 95% exact confidence interval. For each participant, percentage decline in PSA values are calculated as 100% times the difference between PSA values taken at baseline and 12 weeks divided by PSA values at baseline. Percentage of participants determined as 100% times the number of participants with >= 50% decline divided by overall number of participants.

Outcome measures

Measure	Treatment (Enzalutamide) n=34 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Percentage of Participants With a >= 50% Decline in Prostate-specific Antigen (PSA) Value	73.5 percentage of subjects Interval 55.6 to 87.1	—

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Population: For the primary endpoint, evaluable patients will include those patients for whom data from genomic studies and IHC tests are available from the pre-treatment biopsy samples and who have completed at least 12 weeks of therapy or who have confirmed disease progression prior to 12 weeks of therapy. Targeted DNA sequencing was performed on 26 of 36 biopsies that contained sufficient material.

Evaluate the association between PSA response at 12 weeks after initiating therapy, and TP53 copy number alterations and mutations at baseline. Simple Logistic regression was planned but due to sample size we used Fisher's Exact test. Percentage of patients in each arm with TP53 copy number alterations and mutations will be reported and odds ratio with two-sided 95% confidence interval will be calculated.

Outcome measures

Measure	Treatment (Enzalutamide) n=21 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders n=5 Participants PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Percentage of Participants With Tumor Protein 53 Gene (TP53) Copy Number Alterations and Mutations	28.6 percentage of subjects	80.0 percentage of subjects

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Population: For the primary endpoint, evaluable patients will include those patients for whom data from genomic studies and IHC tests are available from the pre-treatment biopsy samples and who have completed at least 12 weeks of therapy or who have confirmed disease progression prior to 12 weeks of therapy. Targeted DNA sequencing was performed on 26 of 36 biopsies that contained sufficient material.

Evaluate the association between PSA response at 12 weeks after initiating therapy, and PTEN copy number alterations and mutations at baseline. Simple Logistic regression was planned but due to sample size we used Fisher's Exact test. Percentage of patients in each arm with PTEN copy number alterations and mutations will be reported and odds ratio with two-sided 95% confidence interval will be calculated.

Outcome measures

Measure	Treatment (Enzalutamide) n=21 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders n=5 Participants PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Percentage of Participants With Phosphatase and Tensin Homologue Gene (PTEN) Copy Number Alterations and Mutations	47.6 percentage of subjects	40.0 percentage of subjects

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Population: For the primary endpoint, evaluable patients will include those patients for whom data from genomic studies and IHC tests are available from the pre-treatment biopsy samples and who have completed at least 12 weeks of therapy or who have confirmed disease progression prior to 12 weeks of therapy. Targeted DNA sequencing was performed on 26 of 36 biopsies that contained sufficient material.

Evaluate the association between PSA response at 12 weeks after initiating therapy, and RB1 copy number alterations and mutations at baseline. Simple Logistic regression was planned but due to sample size we used Fisher's Exact test. Percentage of patients in each arm with RB1 copy number alterations and mutations will be reported and odds ratio with two-sided 95% confidence interval will be calculated.

Outcome measures

Measure	Treatment (Enzalutamide) n=21 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders n=5 Participants PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Percentage of Participants With Retinoblastoma Gene (RB1) Copy Number Alterations and Mutations	9.5 percentage of subjects	0.0 percentage of subjects

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Population: Evaluable patients will include those patients for whom data from genomic studies and IHC tests are available from the pre-treatment biopsy samples and who have completed at least 12 weeks of therapy or who have confirmed disease progression prior to 12 weeks of therapy, and for whom baseline and 12 week PSA data were available. RNA sequencing was performed on 25 of 36 biopsies that contained sufficient material.

Median AR mRNA expression between responders and non-responders.

Outcome measures

Measure	Treatment (Enzalutamide) n=18 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders n=7 Participants PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Androgen Receptor (AR) Messenger RNA (mRNA) Expression	224.9 TPM Standard Deviation 133.2	201.7 TPM Standard Deviation 201.7

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Population: Evaluable patients will include those patients for whom data from genomic studies and IHC tests are available from the pre-treatment biopsy samples and who have completed at least 12 weeks of therapy or who have confirmed disease progression prior to 12 weeks of therapy, and for whom baseline and 12 week PSA data were available. RNA sequencing was performed on 25 of 36 biopsies that contained sufficient material.

Median AR-V7 expression between responders and non-responders.

Outcome measures

Measure	Treatment (Enzalutamide) n=18 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders n=7 Participants PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Androgen Receptor Variant 7 (AR-V7) Expression	10.4 TPM Standard Deviation 7.2	12.3 TPM Standard Deviation 11.8

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Population: For the primary endpoint, evaluable patients will include those patients for whom data from genomic studies and IHC tests are available from the pre-treatment biopsy samples and who have completed at least 12 weeks of therapy or who have confirmed disease progression prior to 12 weeks of therapy. AR immunohistochemistry was available in 22 patients with sufficient samples.

Evaluate the association between PSA response at 12 weeks after initiating therapy, and AR copy number alterations and mutations at baseline. Simple Logistic regression was planned but due to sample size we used Fisher's Exact test. Percentage of patients in each arm with AR copy number alterations and mutations will be reported and odds ratio with two-sided 95% confidence interval will be calculated.

Outcome measures

Measure	Treatment (Enzalutamide) n=19 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders n=3 Participants PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Percentage of Participants With Androgen Receptor (AR) Copy Number Alterations and Mutations	73.7 percentage of subjects	100.0 percentage of subjects

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Population: For the primary endpoint, evaluable patients will include those patients for whom data from genomic studies and IHC tests are available from the pre-treatment biopsy samples and who have completed at least 12 weeks of therapy or who have confirmed disease progression prior to 12 weeks of therapy. AR protein expression was analyzed using immunohistochemical analysis from 21 patients with sufficient samples.

The number of participants, responders and non-responders, that were found to have protein expression of AR.

Outcome measures

Measure	Treatment (Enzalutamide) n=15 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders n=6 Participants PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Number of Participants With Protein Expression of AR	15 participants	6 participants

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Population: Evaluable patients will include those patients for whom data from genomic studies and IHC tests are available from the pre-treatment biopsy samples and who have completed at least 12 weeks of therapy or who have confirmed disease progression prior to 12 weeks of therapy, and for whom baseline and 12 week PSA data were available. RNA sequencing was performed on 25 of 36 biopsies that contained sufficient material.

Median Normalized Enrichment Score (NES) AR activity levels of responders and non-responders. Gene Set Enrichment Analysis (GSEA) is used to interpret gene expression data. GSEA enrichment score (ES) reflects the degree to which a gene set (GS) is overrepresented at the top or bottom of a ranked list of genes. ES is calculated by walking down the list, increasing a running-sum statistic when a gene is in the GS and decreasing when it's not. Magnitude of increment depends on correlation of the gene with the phenotype. ES is the max deviation from zero encountered in walking the list. Positive ES indicates GS enrichment at the top of the list; negative indicates GS enrichment at the bottom. GSEA calculates NES as actual ES divided by mean (ESs against all permutations of the dataset). Low AR activity has been linked to stemness and lineage plasticity that are recognized as a cause of acquired resistance to AR-targeting therapies.

Outcome measures

Measure	Treatment (Enzalutamide) n=18 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders n=7 Participants PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Androgen Receptor (AR) Activity Level	2.2 score on a scale Standard Deviation 3.3	-2.6 score on a scale Standard Deviation 1.4

SECONDARY outcome

Timeframe: Baseline to up to 5 years

Number of patients who achieved a 50% or greater PSA decline any time after 12 weeks post-baseline.

Outcome measures

Measure	Treatment (Enzalutamide) n=34 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Prostate-specific Antigen (PSA) Changes	25 Participants	—

SECONDARY outcome

Timeframe: Baseline to date of first documented radiographic objective response, assessed up to 1 year

Population: Only those subjects who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for objective response.

The percentage of participants with an objective response will be reported with 95% exact confidence interval. Objective radiographic response is evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. For each participant, objective response is calculated as 100% times the difference between the sum of measurable target lesions at baseline and the smallest sum of measurable target lesions achieved after the initiation of therapy, divided by the sum of target lesions at baseline.

Outcome measures

Measure	Treatment (Enzalutamide) n=22 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Percentage of Participants With an Objective Response	63.6 percentage of subjects Interval 40.7 to 82.8	—

SECONDARY outcome

Timeframe: Time from day 1 of study drug treatment to date of first documented radiographic progression or clinical progression, assessed up to 5 years

Correlations between baseline molecular features and pathways and PFS will be assessed using cox regression model. In addition, Kaplan-Meier plots will be used to graphically illustrate the survival distributions across the strata of categorical molecular predictors.

Outcome measures

Measure	Treatment (Enzalutamide) n=25 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders n=9 Participants PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Progression-free Survival (PFS)	23.9 months Interval 10.9 to 33.6	3.7 months Interval 2.0 to 11.0

SECONDARY outcome

Timeframe: Time from day 1 of study drug treatment to date of death from prostate cancer, assessed up to 5 years

Correlations between baseline molecular features and pathways and DSS will be assessed using cox regression model. In addition, Kaplan-Meier plots will be used to graphically illustrate the survival distributions across the strata of categorical molecular predictors.

Outcome measures

Measure	Treatment (Enzalutamide) n=29 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders n=9 Participants PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Disease-specific Survival (DSS)	38.6 months Interval 21.3 to 45.1	16.0 months Interval 4.7 to 23.8

SECONDARY outcome

Timeframe: Time from day 1 of study drug treatment to date of death from any cause, assessed up to 5 years

Correlations between baseline molecular features and pathways and OS will be assessed using cox regression model. In addition, Kaplan-Meier plots will be used to graphically illustrate the survival distributions across the strata of categorical molecular predictors.

Outcome measures

Measure	Treatment (Enzalutamide) n=25 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders n=9 Participants PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Overall Survival (OS)	36.90 months Interval 21.29 to Upper limit of confidence interval not estimable; there are not enough events at later times to get a reliable estimate.	15.97 months Interval 4.65 to 23.8

SECONDARY outcome

Timeframe: Up to 5 years

Correlations between baseline molecular features and pathways and time to PSA progression will be assessed.

Outcome measures

Measure	Treatment (Enzalutamide) n=24 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders n=9 Participants PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Time to Prostate-specific Antigen (PSA) Progression	23.9 months Interval 10.9 to 33.6	3.7 months Interval 2.0 to 11.0

SECONDARY outcome

Timeframe: Up to 5 years

Population: We did not perform a random forest classifier. Rather, we used gene set enrichment analysis to understand transcriptional differences between responders and non-responders.

Random Forests classification will be used to identify molecular features and pathways present in patients with disease progression or who discontinue Enzalutamide treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to up to 5 years

Population: Data were not collected

Linear regression model will be used to assess the association for changes in CTC counts from baseline and maximal prostate-specific antigen (PSA) observed while on study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 12 weeks

Population: Evaluable patients will include those patients for whom data from genomic studies and IHC tests are available from the pre-treatment biopsy samples and who have completed at least 12 weeks of therapy or who have confirmed disease progression prior to 12 weeks of therapy, and for whom baseline and 12 week PSA data were available. 36 subjects shown in participant flow. 2 subjects were excluded from this PSA analysis: 1 had missing PSA data, 1 had falling PSA in setting of rapid disease progression

Degree of prostate-specific antigen (PSA) change from baseline to 12 weeks. PSA at week 12 minus PSA at baseline divided by PSA at baseline and multiplied by 100%. Decline shown as negative percent and incline shown as positive percent.

Outcome measures

Measure	Treatment (Enzalutamide) n=25 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders n=9 Participants PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Degree of Prostate-specific Antigen (PSA) Decline	-86.7 percentage of PSA at baseline Standard Deviation 13.5	101.8 percentage of PSA at baseline Standard Deviation 140.2

SECONDARY outcome

Timeframe: Up to 5 years

Population: Data were not collected

Correlations between baseline molecular features and pathways and maximal PSA decline observed will be assessed. Linear regression model will be used to assess the association for changes in circulating tumor cells (CTC) counts from baseline and maximal PSA observed while on study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 5 years

The association between molecular predictors and survival outcomes (e.g., progression-free survival [PFS], disease-free survival [DSS] and overall survival [OS]) and time on treatment will be assessed using cox regression model.

Outcome measures

Measure	Treatment (Enzalutamide) n=25 Participants Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO	PSA Non-responders n=9 Participants PSA Non-Responder: A less than 50% reduction at 12 weeks after the initiation of therapy vs. baseline. Baseline PSA will be defined as the measurement obtained immediately prior to initiation of Enzalutamide on Day 1 of study.
Time on Treatment	24.23 months Interval 11.55 to 40.35	3.43 months Interval 2.29 to 14.59

Adverse Events

Treatment (Enzalutamide)

Serious events: 6 serious events

Other events: 36 other events

Deaths: 2 deaths

Serious adverse events

Measure	Treatment (Enzalutamide) n=36 participants at risk Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO
Injury, poisoning and procedural complications fracture	2.8% 1/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Renal and urinary disorders Acute kidney injury	2.8% 1/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Blood and lymphatic system disorders Anemia	2.8% 1/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Cardiac disorders Atrial fibrillation	2.8% 1/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	2.8% 1/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
General disorders Disease progression	2.8% 1/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Cardiac disorders Heart failure	2.8% 1/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Renal and urinary disorders Hematuria	2.8% 1/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Vascular disorders Hypotension	2.8% 1/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Nervous system disorders Intracranial hemorrhage	2.8% 1/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Nervous system disorders Encephalopathy	2.8% 1/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Renal and urinary disorders Renal and urinary disorders - other, kidney cancer	2.8% 1/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Infections and infestations Sepsis	2.8% 1/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Infections and infestations Soft tissue infection	2.8% 1/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Infections and infestations Urinary tract infection	5.6% 2/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.

Other adverse events

Measure	Treatment (Enzalutamide) n=36 participants at risk Patients receive enzalutamide PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo a tumor biopsy of a metastatic site at study entry (prior to initiation of enzalutamide) and after the time of progression. Per the investigator, patients may continue treatment beyond progression. Enzalutamide: Given PO
Psychiatric disorders depression	8.3% 3/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Gastrointestinal disorders diarrhea	8.3% 3/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Nervous system disorders dizziness	11.1% 4/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Respiratory, thoracic and mediastinal disorders dyspnea	11.1% 4/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Nervous system disorders Dysgeusia	8.3% 3/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
General disorders edema limbs	11.1% 4/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Injury, poisoning and procedural complications fall	33.3% 12/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Injury, poisoning and procedural complications fracture	25.0% 9/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Reproductive system and breast disorders Gynecomastia	8.3% 3/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Renal and urinary disorders Hematuria	8.3% 3/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Vascular disorders Hot flashes	11.1% 4/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Vascular disorders Hypertension	8.3% 3/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Metabolism and nutrition disorders Hypokalemia	8.3% 3/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Psychiatric disorders Insomnia	8.3% 3/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Musculoskeletal and connective tissue disorders Myalgia	5.6% 2/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Gastrointestinal disorders Nausea	13.9% 5/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Nervous system disorders Nervous system disorders - Other, neuropathy	8.3% 3/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
General disorders pain	22.2% 8/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Gastrointestinal disorders Abdominal pain	5.6% 2/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 2/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Musculoskeletal and connective tissue disorders back pain	8.3% 3/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, hip pain	22.2% 8/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, shoulder pain	5.6% 2/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Nervous system disorders Paresthesia	8.3% 3/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Nervous system disorders Presyncope	5.6% 2/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Skin and subcutaneous tissue disorders Pruritus	5.6% 2/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Infections and infestations Skin infection	5.6% 2/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Nervous system disorders Stroke	11.1% 4/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Infections and infestations Upper respiratory infection	13.9% 5/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Renal and urinary disorders Urinary incontinence	5.6% 2/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Renal and urinary disorders Urinary retention	5.6% 2/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Infections and infestations Urinary tract infection	11.1% 4/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
Investigations Weight loss	5.6% 2/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.
General disorders fatigue	47.2% 17/36 • Median time period for adverse events 14 months (range 2 months to 53 months). Deaths assessed up to 5 years. Collected from the start date of treatment with enzalutamide to the last date of treatment with enzalutamide. Adverse events are collected for any untoward clinical experience with the exception of lab abnormalities which are only reported if the test result is deemed Clinically Significant by the responsible or treating physician. Clinical significance is based on clinical judgement and individual patient situation, at the discretion of the physician. Deaths assessed up to 5 years.

Additional Information

Dr. Alexandra Sokolova, M.D.

Oregon Health & Science University

Phone: (503) 494-4396

Email: sokolova@ohsu.edu

Results disclosure agreements

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