Trial Outcomes & Findings for Early Switch From First-Line Docetaxel/Prednisone to Cabazitaxel/Prednisone and the Opposite Sequence, Exploring Molecular Markers in Men With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (NCT NCT01718353)

Last Updated: 2017-11-20

Results Overview

PSA response was defined as ≥50% decrease in PSA levels in both treatment arms from baseline, during the whole treatment, before treatment switch and after treatment switch. PSA progression was defined as decline of PSA from baseline (an increase of ≥25% \[at least 2ng/ml\] over the nadir value, confirmed by a second PSA value at least 3 weeks apart) and no decline of PSA from baseline (an increase of ≥25% \[at least 2ng/ml\] over the baseline value after 12 weeks of treatment, confirmed by a second PSA value at least 3 weeks apart). Because the purpose of this study is to explore the benefit of a regimen in which participants are switched to a different taxane if PSA does not decrease ≥30% after 4 cycles, irrespective of which agent (docetaxel or cabazitaxel) is administered initially, the data for participants who began treatment with docetaxel and for those who began treatment with cabazitaxel were combined for the efficacy analyses.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

63 participants

Primary outcome timeframe

Baseline, Pre-dose every 3 weeks, 30 days after last treatment administration (End of treatment [EOT]), every 3 months (for 1 year) then every 6 months until PSA progression or study cut-off, whichever was earlier (Maximum duration: 60 weeks)

Results posted on

2017-11-20

Participant Flow

The study was conducted at 19 centers in Canada and United States. A total of 81 participants were screened between 20 March 2013 and 29 May 2014, of which, 63 participants were randomized and 61 were treated. A total of 18 participants were screen failure mainly due to exclusion criteria met and inclusion criteria not met.

Participants were randomized by Interactive Voice Response System (IVRS) in 2:1 ratio (Treatment A : Treatment B) to receive either Treatment A (Docetaxel + Prednisone) or Treatment B (Cabazitaxel + Prednisone).

Participant milestones

Participant milestones
Measure	Docetaxel + Prednisone (Treatment A) Docetaxel 75 mg/m\^2 intravenous (IV) infusion on Day 1 of Cycle 1 and every 3 weeks (q3w) thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% prostate-specific antigen (PSA) reduction from baseline at the end of Cycle 4 switched to Cabazitaxel 25mg/m\^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until disease progression (DP), death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.	Cabazitaxel + Prednisone (Treatment B) Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4 switched to Docetaxel 75mg/m\^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.
Overall Study STARTED	41	22
Overall Study Treated	39	22
Overall Study Treated up to End of Cycle 4	32	16
Overall Study Treated From Cycle 5	23	25
Overall Study COMPLETED	29	17
Overall Study NOT COMPLETED	12	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Docetaxel + Prednisone (Treatment A) Docetaxel 75 mg/m\^2 intravenous (IV) infusion on Day 1 of Cycle 1 and every 3 weeks (q3w) thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% prostate-specific antigen (PSA) reduction from baseline at the end of Cycle 4 switched to Cabazitaxel 25mg/m\^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until disease progression (DP), death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.	Cabazitaxel + Prednisone (Treatment B) Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4 switched to Docetaxel 75mg/m\^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.
Overall Study Lost to Follow-up	0	1
Overall Study Principal Investigator's Decision	10	4
Overall Study Randomized but not treated	2	0

Baseline Characteristics

Early Switch From First-Line Docetaxel/Prednisone to Cabazitaxel/Prednisone and the Opposite Sequence, Exploring Molecular Markers in Men With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Docetaxel + Prednisone (Treatment A) n=41 Participants Docetaxel 75 mg/m\^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4 switched to Cabazitaxel 25mg/m\^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.	Cabazitaxel + Prednisone (Treatment B) n=22 Participants Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4 switched to Docetaxel 75mg/m\^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.	Total n=63 Participants Total of all reporting groups
Age, Continuous	69.9 years STANDARD_DEVIATION 7.8 • n=93 Participants	69.2 years STANDARD_DEVIATION 9.5 • n=4 Participants	69.7 years STANDARD_DEVIATION 8.4 • n=27 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Male	41 Participants n=93 Participants	22 Participants n=4 Participants	63 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline, Pre-dose every 3 weeks, 30 days after last treatment administration (End of treatment [EOT]), every 3 months (for 1 year) then every 6 months until PSA progression or study cut-off, whichever was earlier (Maximum duration: 60 weeks)

Population: Analysis was performed on all randomized participants.

Outcome measures

Outcome measures
Measure	Overall Population (Treatment A or Treatment B) n=63 Participants Docetaxel 75 mg/m\^2 or Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m\^2 IV or Docetaxel 75mg/m\^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.	Overall Population (Non AR-target Agent Treated) Participants not having prior treatment experience with a high potency AR targeted agent (AR signaling inhibitor or CYP 17 inhibitor) before this study.
Percentage of Participants With PSA Response PSA response before switch	39.7 percentage of participants	—
Percentage of Participants With PSA Response PSA response after switch	15.9 percentage of participants	—
Percentage of Participants With PSA Response Overall PSA response	55.6 percentage of participants	—

PRIMARY outcome

Timeframe: Baseline and Cycle 1 Day 8, Cycle 4

Population: Participants with evaluable CTCs at both baseline and Cycle 1 Day 8, and evaluable PSA result at both baseline and Cycle 4

Analysis of CTCs is a co-primary endpoint. Growth of prostate cancer cells is dependent on sustained androgen receptor (AR) nuclear signaling. Taxanes (e.g., docetaxel and cabazitaxel) may mediate some of their activity in prostate cancer by impairing AR trafficking along the microtubules from the tumor cell cytoplasm into the nucleus, as a result of taxane-induced microtubule bundling (MTB). Blood samples were collected at baseline and post-treatment to allow isolation of CTCs, which were evaluated for tumor cell biomarker measures %ARNL and MTB score. %ARNL was assessed by quantitative analysis of images of CTCs captured by geometrically enhanced differential immunocapture (GEDI). Reduction from baseline in %ARNL (percentage of total cellular AR that is located in the nucleus) may indicate inhibition of AR signaling. Change from baseline in %ARNL at Cycle 1 Day 8 is summarized by categories of participants with PSA decrease from baseline (≥50%, Not ≥50%) after Cycle 4.

Outcome measures

Outcome measures
Measure	Overall Population (Treatment A or Treatment B) n=19 Participants Docetaxel 75 mg/m\^2 or Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m\^2 IV or Docetaxel 75mg/m\^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.	Overall Population (Non AR-target Agent Treated) Participants not having prior treatment experience with a high potency AR targeted agent (AR signaling inhibitor or CYP 17 inhibitor) before this study.
Drug-target Engagement in Circulating Tumor Cells (CTCs): Change From Baseline at Cycle 1 Day 8 in Percent Androgen Receptor Nuclear Localization (%ARNL) by Categories of PSA Decrease From Baseline (≥50%, Not ≥50%) After Cycle 4 PSA decreased ≥50% at Cycle 4	-17.58 percentage ARNL Standard Deviation 21.54	—
Drug-target Engagement in Circulating Tumor Cells (CTCs): Change From Baseline at Cycle 1 Day 8 in Percent Androgen Receptor Nuclear Localization (%ARNL) by Categories of PSA Decrease From Baseline (≥50%, Not ≥50%) After Cycle 4 PSA not decreased ≥50% at Cycle 4	2.30 percentage ARNL Standard Deviation 11.16	—

PRIMARY outcome

Timeframe: Baseline and Cycle 1 Day 8, Cycle 4

Population: Participants with evaluable CTCs at both baseline and Cycle 1 Day 8, and evaluable PSA result at both baseline and Cycle 4

Analysis of CTCs is a co-primary endpoint. Growth of prostate cancer cells is dependent on sustained AR nuclear signaling. Taxanes (e.g., docetaxel and cabazitaxel) may mediate some of their activity in prostate cancer by impairing AR trafficking along the microtubules from the tumor cell cytoplasm into the nucleus, as a result of taxane-induced MTB. Blood samples were collected at baseline and post-treatment to allow isolation of CTCs, which were evaluated for tumor cell biomarker measures %ARNL and MTB score. MTB in images of CTCs captured by GEDI was qualitatively assessed by three independent operators for increase compared with baseline on a scale of 0 to 3 from no to most MTB increase. Increase from baseline in MTB may indicate inhibition of AR signaling. Change from baseline in MTB at Cycle 1 Day 8 is summarized by categories of participants with PSA decrease from baseline (≥30%, Not ≥30%) after Cycle 4.

Outcome measures

Outcome measures
Measure	Overall Population (Treatment A or Treatment B) n=19 Participants Docetaxel 75 mg/m\^2 or Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m\^2 IV or Docetaxel 75mg/m\^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.	Overall Population (Non AR-target Agent Treated) Participants not having prior treatment experience with a high potency AR targeted agent (AR signaling inhibitor or CYP 17 inhibitor) before this study.
Drug-target Engagement in CTCs: Change From Baseline at Cycle 1 Day 8 in MTB by Categories of PSA Decrease From Baseline (≥30%, Not ≥30%) After Cycle 4 PSA decreased ≥30% at Cycle 4	0.69 units on a scale Standard Deviation 0.87	—
Drug-target Engagement in CTCs: Change From Baseline at Cycle 1 Day 8 in MTB by Categories of PSA Decrease From Baseline (≥30%, Not ≥30%) After Cycle 4 PSA not decreased ≥30% at Cycle 4	0.09 units on a scale Standard Deviation 0.18	—

SECONDARY outcome

Timeframe: From Baseline until DP or death due to any cause or study cut off, whichever was earlier (Maximum duration: 60 weeks)

Population: Analysis was performed on all randomized participants.

PFS was defined as the time interval between the date of random allocation of the treatment and the date of first documentation of any of the following: radiographic tumor progression (using Modified Response Evaluation Criteria in Solid Tumors \[RECIST1.1\] before any switch and during the study), clinical progression (including skeletal-related events, increasing pain requiring escalation of narcotic analgesics, urinary obstruction), PSA progression or death from any cause. Analysis was performed by Kaplan Meier method.

Outcome measures

Outcome measures
Measure	Overall Population (Treatment A or Treatment B) n=63 Participants Docetaxel 75 mg/m\^2 or Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m\^2 IV or Docetaxel 75mg/m\^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.	Overall Population (Non AR-target Agent Treated) Participants not having prior treatment experience with a high potency AR targeted agent (AR signaling inhibitor or CYP 17 inhibitor) before this study.
Progression Free Survival (PFS) Before switch	4.1 months Interval 3.81 to The upper bound of the confidence interval could not be estimated because of insufficient number of events for before switch PFS.	—
Progression Free Survival (PFS) Whole treatment continuum	9.1 months Interval 4.93 to 11.7	—

SECONDARY outcome

Timeframe: From Baseline until DP or death due to any cause or study cut off date, whichever was earlier (Maximum duration: 60 weeks)

Population: Analysis was performed on all randomized population.

PSA progression-free survival before any switch and PSA progression free survival during the study was defined as the time interval between the date of Day 1 of Cycle 1 to the date of either first PSA progression or death due to any cause whichever came first. PSA progression was defined as decline of PSA from baseline (an increase of ≥25% \[at least 2ng/mL\] over the nadir value, confirmed by a second PSA value at least 3 weeks apart) and no decline of PSA from baseline (an increase of ≥25% \[at least 2ng/mL\] over the baseline value after 12 weeks of treatment, confirmed by a second PSA value at least 3 weeks apart).

Outcome measures

Outcome measures
Measure	Overall Population (Treatment A or Treatment B) n=63 Participants Docetaxel 75 mg/m\^2 or Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m\^2 IV or Docetaxel 75mg/m\^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.	Overall Population (Non AR-target Agent Treated) Participants not having prior treatment experience with a high potency AR targeted agent (AR signaling inhibitor or CYP 17 inhibitor) before this study.
PSA Progression Free Survival Before switch	NA months Interval 3.09 to The median and upper bound of the confidence interval could not be estimated because of insufficient number of events for before switch PSA PFS.	—
PSA Progression Free Survival whole treatment continuum	12.4 months Interval 8.31 to The upper bound of the confidence interval could not be estimated because of insufficient number of events for whole treatment continuum PSA PFS.	—

SECONDARY outcome

Timeframe: From baseline until DP or study cut off, whichever was earlier (Maximum duration: 60 weeks)

Population: No data was collected to determine the Objective Response, hence this outcome measure was not evaluated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From baseline, every 12 weeks until radiological tumor progression or study cut-off, whichever was earlier (Maximum duration: 60 weeks)

Population: Analysis was performed on all randomized participants.

Outcome measures

Outcome measures
Measure	Overall Population (Treatment A or Treatment B) n=63 Participants Docetaxel 75 mg/m\^2 or Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m\^2 IV or Docetaxel 75mg/m\^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.	Overall Population (Non AR-target Agent Treated) Participants not having prior treatment experience with a high potency AR targeted agent (AR signaling inhibitor or CYP 17 inhibitor) before this study.
Radiographic Progression-free Survival (rPFS)	NA months Kaplan-Meier was not analyzed, as less than 50% population had the event. Hence, data was not calculated and reported.	—

SECONDARY outcome

Timeframe: Baseline, Pre-dose every 3 weeks, EOT, every 3 months (for 1 year) until first SRE occurrence or death or study cut-off, whichever was earlier (Maximum duration: 60 weeks)

Population: Analysis was performed on all randomized participants.

cPFS was assessed before switch and during the study including skeletal-related events (SRE), increasing pain requiring escalation of narcotic analgesics, urinary obstruction, etc. SRE included pathological fractures and/or spinal cord compression, need for bone irradiation (including radioisotopes or bone surgery), change of antineoplastic therapy (including introduction of bisphosphonates or denosumab in the face of increase in pain) to treat bone pain. Pain was assessed using present pain intensity (PPI) scale (0=no pain, up to 5=excruciating pain) and analgesics used for cancer pain (1 point for non-narcotic medications and 4 points for narcotic medications).

Outcome measures

Outcome measures
Measure	Overall Population (Treatment A or Treatment B) n=63 Participants Docetaxel 75 mg/m\^2 or Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m\^2 IV or Docetaxel 75mg/m\^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.	Overall Population (Non AR-target Agent Treated) Participants not having prior treatment experience with a high potency AR targeted agent (AR signaling inhibitor or CYP 17 inhibitor) before this study.
Clinical Progression-free Survival (cPFS) Before switch	NA months Interval 7.16 to The median and upper bound of the confidence interval could not be estimated because of insufficient number of events for before switch cPFS.	—
Clinical Progression-free Survival (cPFS) Whole treatment continuum	NA months Kaplan-Meier was not analyzed, as less than 50% population had the event. Hence, data was not calculated and reported.	—

SECONDARY outcome

Timeframe: From baseline until death due to any cause or study cut-off, whichever was earlier (Maximum duration: 60 weeks)

Population: Analysis was performed on all randomized participants.

Overall survival before switch and overall survival during the study was defined as the time interval from the date of random allocation to the date of death due to any cause until study cut-off date.

Outcome measures

Outcome measures
Measure	Overall Population (Treatment A or Treatment B) n=63 Participants Docetaxel 75 mg/m\^2 or Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m\^2 IV or Docetaxel 75mg/m\^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.	Overall Population (Non AR-target Agent Treated) Participants not having prior treatment experience with a high potency AR targeted agent (AR signaling inhibitor or CYP 17 inhibitor) before this study.
Overall Survival Before switch	8.8 Months Interval 4.01 to Not enough events were reported to calculate Kaplan-Meier curve.	—
Overall Survival whole treatment continuum	NA Months Interval 14.03 to Not enough events were reported to calculate Kaplan-Meier curve.	—

SECONDARY outcome

Timeframe: From baseline until DP or study cut-off, whichever was earlier (Maximum duration: 60 weeks)

Population: Analysis was performed on as-treated population that included all participants who received initial taxane treatment and had a post treatment assessment. Number of participants analyzed=participants treated/non-treated with AR-target agent and with PSA response assessment at specified time-points.

Participants with ≥30% and ≥50% reduction in PSA response from base line were evaluated in participants who were previously treated with a high potency androgen receptor (AR)-targeted agent (AR signaling inhibitor or cytochrome P450 17 alphahydroxylase/17,20lyase \[CYP 17\] inhibitor).

Outcome measures

Outcome measures
Measure	Overall Population (Treatment A or Treatment B) n=25 Participants Docetaxel 75 mg/m\^2 or Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4, switched to Cabazitaxel 25 mg/m\^2 IV or Docetaxel 75mg/m\^2 IV infusion respectively on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.	Overall Population (Non AR-target Agent Treated) n=35 Participants Participants not having prior treatment experience with a high potency AR targeted agent (AR signaling inhibitor or CYP 17 inhibitor) before this study.
Percentage of Participants With ≥30% and ≥50% Reduction in PSA Response ≥30% reduction	52.0 percentage of participants	74.3 percentage of participants
Percentage of Participants With ≥30% and ≥50% Reduction in PSA Response ≥50% reduction	44.0 percentage of participants	68.6 percentage of participants

Adverse Events

Docetaxel + Prednisone (Treatment A) - Throughout

Serious events: 10 serious events

Other events: 26 other events

Deaths: 0 deaths

Cabazitaxel + Prednisone (Treatment B) - Throughout

Serious events: 8 serious events

Other events: 18 other events

Deaths: 0 deaths

Switched Population (Treatment A to B or Treatment B to A)

Serious events: 9 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER