Trial Outcomes & Findings for Darolutamide in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer (NCT NCT02799602)

Last Updated: 2025-12-04

Results Overview

Overall survival (OS) was defined as the time from the date of randomization until death from any cause. Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data. Long-term (Survival) follow-up period: After Active follow-up, patients continued to be contacted approximately every 12 weeks by phone. The end of the Survival follow-up period was defined as when the patient died, was lost to follow-up, withdrew consent, or at the end-of-study.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1306 participants

Primary outcome timeframe

From randomization of the first participant until death from any cause up to 25 OCT 2021 cut-off date 533 OS events were reached (approximate 59 months)

Results posted on

2025-12-04

Participant Flow

This multinational study was conducted between 30-Nov-2016 First Participant First Visit and 11-Apr-2023 Last Participant Last Visit, in 23 countries/regions: Australia, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, Finland, France, Germany, Israel, Italy, Japan, Mexico, Netherlands, Poland, Russian Federation, South Korea, Spain, Sweden, Taiwan, UK, US

1306 were randomly assigned in a 1:1 ratio to study treatment and 1305 were considered valid for efficacy analyses. A total of 1302 participants started treatment and were included to safety analyses.

Participant milestones

Participant milestones
Measure	Darolutamide (BAY1841788) + Docetaxel Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Overall Study STARTED	651	654
Overall Study Started Treatment	651	651
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	651	654

Reasons for withdrawal

Reasons for withdrawal
Measure	Darolutamide (BAY1841788) + Docetaxel Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Overall Study Protocol Violation	1	0
Overall Study Physician Decision	5	6
Overall Study Lost to Follow-up	4	2
Overall Study Additional primary malignancy	11	6
Overall Study Non-compliance with study drug	14	12
Overall Study Adverse event associated with clinical disease progression	24	26
Overall Study Withdrawal by Subject	26	40
Overall Study Progressive disease - clinical progression	131	276
Overall Study Progressive disease - radiological progression	90	133
Overall Study Adverse event not associated with clinical disease progression	49	27
Overall Study Death	9	5
Overall Study Other	287	118
Overall Study Study drug never administered	0	3

Baseline Characteristics

Darolutamide in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Total n=1305 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants
Age, Categorical Between 18 and 65 years	243 Participants n=3 Participants	234 Participants n=3 Participants	477 Participants n=6 Participants
Age, Categorical >=65 years	408 Participants n=3 Participants	420 Participants n=3 Participants	828 Participants n=6 Participants
Sex: Female, Male Female	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants
Sex: Female, Male Male	651 Participants n=3 Participants	654 Participants n=3 Participants	1305 Participants n=6 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	40 Participants n=3 Participants	49 Participants n=3 Participants	89 Participants n=6 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	561 Participants n=3 Participants	557 Participants n=3 Participants	1118 Participants n=6 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	50 Participants n=3 Participants	48 Participants n=3 Participants	98 Participants n=6 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Asian	231 Participants n=3 Participants	245 Participants n=3 Participants	476 Participants n=6 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Black or African American	26 Participants n=3 Participants	28 Participants n=3 Participants	54 Participants n=6 Participants
Race (NIH/OMB) White	345 Participants n=3 Participants	333 Participants n=3 Participants	678 Participants n=6 Participants
Race (NIH/OMB) More than one race	6 Participants n=3 Participants	2 Participants n=3 Participants	8 Participants n=6 Participants
Race (NIH/OMB) Unknown or Not Reported	43 Participants n=3 Participants	46 Participants n=3 Participants	89 Participants n=6 Participants

PRIMARY outcome

Timeframe: From randomization of the first participant until death from any cause up to 25 OCT 2021 cut-off date 533 OS events were reached (approximate 59 months)

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
OS From Date of Randomization Until Death From Any Cause - Number of Events Number of patients with event	229 Participants	304 Participants
OS From Date of Randomization Until Death From Any Cause - Number of Events Number of patients censored	422 Participants	350 Participants

PRIMARY outcome

Timeframe: From randomization of the first participant until death from any cause up to 25 OCT 2021 cut-off date 533 OS events were reached (approximate 59 months)

Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data. Long-term (Survival) follow-up period: After Active follow-up, patients continued to be contacted approximately every 12 weeks by phone. The end of the Survival follow-up period was defined as when the patient died, was lost to follow-up, withdrew consent, or at the end-of-study. Median, percentile and other 95% CIs were computed using Kaplan-Meier estimates. NA = Value cannot be estimated due to censored data

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
OS From Date of Randomization Until Death From Any Cause - Month	NA Month NA = Value cannot be estimated due to censored data	48.9 Month Interval 44.4 to NA = Value cannot be estimated due to censored data

SECONDARY outcome

Timeframe: From the first dose of darolutamide or placebo until 30 days after the last dose of darolutamide or placebo administration up to cut-off date for the final completion analysis 11 APR 2023 (approximately 77 months)

Population: The number of patients who started treatment is presented based on the randomized treatment assignment. One patient was randomized to the placebo+docetaxel arm but received at least one dose of darolutamide. This patient was included in the darolutamide+docetaxel arm in the analysis of all safety variables.

TEAEs = Treatment-emergent adverse events, were defined as any event(s) arising or worsening after the first dose of darolutamide or placebo, until 30 days after the last dose of darolutamide or placebo administration.

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=652 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=650 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Number of Participants With TEAEs TEAE leading to study drug dose modification	172 Participants	112 Participants
Number of Participants With TEAEs TEAE leading to permanent discontinuation of study drug	90 Participants	69 Participants
Number of Participants With TEAEs TEAE leading to docetaxel dose modification	216 Participants	214 Participants
Number of Participants With TEAEs TEAE leading to permanent discontinuation of docetaxel	52 Participants	67 Participants
Number of Participants With TEAEs Related to protocol-required procedure	69 Participants	64 Participants
Number of Participants With TEAEs Any study drug-related TEAE	344 Participants	309 Participants
Number of Participants With TEAEs Study drug-related TESAE	30 Participants	24 Participants
Number of Participants With TEAEs Study drug-related TEAE leading to study drug dose modification	75 Participants	41 Participants
Number of Participants With TEAEs Study drug-related TEAE leading to permanent discontinuation of study drug	25 Participants	13 Participants
Number of Participants With TEAEs Any TEAE	649 Participants	643 Participants
Number of Participants With TEAEs TESAE	306 Participants	276 Participants

SECONDARY outcome

Timeframe: From randomization of the first participant to the first occurrence of an CRPC event up to 25 OCT 2021 cut-off date approximately 59 months

Time to castration-resistant prostate cancer was defined as the time from randomization to the first occurrence of one of the following events: PSA progression, Radiological progression by bone lesions, or Radiological progression by soft tissue and visceral lesions. Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Time to Castration-Resistant Prostate Cancer (CRPC) - Number of Events Number of patients with event	225 Participants	391 Participants
Time to Castration-Resistant Prostate Cancer (CRPC) - Number of Events Number of patients censored	426 Participants	263 Participants

SECONDARY outcome

Timeframe: From randomization of the first participant to the first occurrence of an CRPC event up to 25 OCT 2021 cut-off date approximately 59 months

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Time to Castration-Resistant Prostate Cancer (CRPC) - Month	NA Months NA = Value cannot be estimated due to censored data	19.1 Months Interval 16.5 to 21.8

SECONDARY outcome

Timeframe: From randomization of the first participant to the first occurrence of a pain progression event up to 25 OCT 2021 cut-off date approximately 59 months

Time to pain progression was defined as the time from randomization to the first date a patient experienced pain progression. Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Time to Pain Progression - Number of Events Number of patients with event	222 Participants	248 Participants
Time to Pain Progression - Number of Events Number of patients censored	429 Participants	406 Participants

SECONDARY outcome

Timeframe: From randomization of the first participant to the first occurrence of a pain progression event up to 25 OCT 2021 cut-off date approximately 59 months

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Time to Pain Progression - Month	NA Months Interval 30.5 to NA = Value cannot be estimated due to censored data	27.5 Months Interval 22.0 to 36.1

SECONDARY outcome

Timeframe: From randomization of the first participant to the first occurrence of an SSE event or death from any cause, whichever occurred first up to 25 OCT 2021 cut-off date approximately 59 months

Symptomatic skeletal event-free survival (SSE-FS) was defined as the time from randomization to the first occurrence of an SSE or death from any cause, whichever occurred first. Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Symptomatic Skeletal Event Free Survival (SSE-FS) - Number of Events Number of patients with event	257 Participants	329 Participants
Symptomatic Skeletal Event Free Survival (SSE-FS) - Number of Events Number of patients censored	394 Participants	325 Participants

SECONDARY outcome

Timeframe: From randomization of the first participant to the first occurrence of an SSE event or death from any cause, whichever occurred first up to 25 OCT 2021 cut-off date approximately 59 months

Symptomatic skeletal event-free survival (SSE-FS) was defined as the time from randomization to the first occurrence of an SSE or death from any cause, whichever occurred first. Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data. NA = Value cannot be estimated due to censored data

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Symptomatic Skeletal Event Free Survival (SSE-FS) - Month	51.2 Months Interval 47.2 to NA = Value cannot be estimated due to censored data	39.7 Months Interval 36.0 to 42.3

SECONDARY outcome

Timeframe: From randomization of the first participant to the first occurrence of an SSE event up to 25 OCT 2021 cut-off date approximately 59 months

Time to the first SSE was defined as the time from randomization to the first occurrence of an SSE. Identical to the definition used for SSE-FS. Death was not considered as an event in this endpoint. Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Time to First Symptomatic Skeletal Event (SSE) - Number of Events Number (%) of patients with event	95 Participants	108 Participants
Time to First Symptomatic Skeletal Event (SSE) - Number of Events Number (%) of patients censored	556 Participants	546 Participants

SECONDARY outcome

Timeframe: From randomization of the first participant to the first occurrence of an SSE event up to 25 OCT 2021 cut-off date approximately 59 months

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Time to First Symptomatic Skeletal Event (SSE) - Month	NA Months NA = Value cannot be estimated due to censored data	NA Months NA = Value cannot be estimated due to censored data

SECONDARY outcome

Timeframe: From randomization of the first participant to the initiation of first subsequent systemic antineoplastic therapy up to 25 OCT 2021 cut-off date approximately 59 months

Time to initiation of subsequent systemic antineoplastic therapy was defined as the time from randomization to the initiation of first subsequent systemic antineoplastic therapy. Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Time to Initiation of Subsequent Antineoplastic Therapy - Number of Events Number (%) of patients with event	219 Participants	395 Participants
Time to Initiation of Subsequent Antineoplastic Therapy - Number of Events Number (%) of patients censored	432 Participants	259 Participants

SECONDARY outcome

Timeframe: From randomization of the first participant to the initiation of first subsequent systemic antineoplastic therapy up to 25 OCT 2021 cut-off date approximately 59 months

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Time to Initiation of Subsequent Antineoplastic Therapy - Month	NA Months NA = Value cannot be estimated due to censored data	25.3 Months Interval 23.1 to 28.8

SECONDARY outcome

Timeframe: From randomization of the first participant to the first increase in disease-related physical symptoms based on the NCCN-FACT-FPSI-17 questionnaire up to 25 OCT 2021 cut-off date approximately 59 months

Time to worsening of disease-related physical symptoms was defined as the time from randomization to the first date a patient experienced an increase in disease-related physical symptoms based on the NCCN-FACT-FPSI-17 questionnaire. Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Time to Worsening of Disease-Related Physical Symptoms - Number of Events Number (%) of patients with event	351 Participants	308 Participants
Time to Worsening of Disease-Related Physical Symptoms - Number of Events Number (%) of patients censored	300 Participants	346 Participants

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Time to Worsening of Disease-Related Physical Symptoms - Month	19.3 Months Interval 13.8 to 24.8	19.4 Months Interval 15.4 to 27.6

SECONDARY outcome

Timeframe: From randomization of the first participant to the first opioid use for ≥7 consecutive days up to 25 OCT 2021 cut-off date approximately 59 months

Time to the initiation of opioid use for ≥7 consecutive days was defined as the time fromrandomization to the date of the first opioid use for ≥7 consecutive days. Data of opioid use related to cancer pain was included in the analysis, and opioid use for non-malignant causes was excluded. Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Time to Initiation of Opioid Use for ≥7 Consecutive Days - Number of Events Number of patients with event	92 Participants	117 Participants
Time to Initiation of Opioid Use for ≥7 Consecutive Days - Number of Events Number of patients censored	559 Participants	537 Participants

SECONDARY outcome

Timeframe: From randomization of the first participant to the first opioid use for ≥7 consecutive days up to 25 OCT 2021 cut-off date approximately 59 months

Outcome measures

Outcome measures
Measure	Darolutamide (BAY1841788) + Docetaxel n=651 Participants Participants received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.	Placebo + Docetaxel n=654 Participants Participants received matching placebo to darolutamide in addition to their standard treatment with docetaxel and androgen deprivation therapy (ADT). Docetaxel was administered for six cycles after randomization. The first cycle of docetaxel was administered within 6 weeks after start of study drug. ADT administration started ≤12 weeks before randomization.
Time to Initiation of Opioid Use for ≥7 Consecutive Days - Month	NA Months NA = Value cannot be estimated due to censored data	NA Months NA = Value cannot be estimated due to censored data

Adverse Events

Darolutamide (BAY1841788) + Docetaxel

Serious events: 306 serious events

Other events: 636 other events

Deaths: 231 deaths

Placebo + Docetaxel

Serious events: 276 serious events

Other events: 634 other events

Deaths: 305 deaths

Serious adverse events

Other adverse events

Additional Information

Therapeutic Area Head

Bayer AG

Phone: 1-888-8422937

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bayer may recommend any changes to the Publication as deemed necessary for scientific purposes. If the Publication could hinder the ability to obtain patent protection for any Invention, Bayer may request a delay of the Publication for a reasonable period to be able to file the patent application, but not to exceed 6 months from the date publication is received for review. Bayer may request further delay in case the patent application has been filed and the priority application is incomplete.
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Restriction type: OTHER