Trial Outcomes & Findings for Cabazitaxel at 20 mg/m² Compared to 25 mg/m² With Prednisone for the Treatment of Metastatic Castration Resistant Prostate Cancer (NCT NCT01308580)

Last Updated: 2017-04-17

Results Overview

OS was defined as the time interval from the date of randomization to the date of death due to any cause. In absence of confirmation of death, survival time was censored at the earlier of the last date the participant was known to be alive or the study cut-off date. The cut-off date for the final analysis of OS was the date when the 988th death had been observed. Analysis was performed by Kaplan-Meier method.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1200 participants

Primary outcome timeframe

From baseline up to death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)

Results posted on

2017-04-17

Participant Flow

The study was conducted at 172 centers in 22 countries. A total of 1463 participants were screened between 19 April 2011 and 18 November 2013. Out of 1463 participants, 1200 participants were enrolled in this study and 263 were not eligible to join the study.

Participants were randomized by Interactive Voice Response System (IVRS) in 1:1 ratio (Cabazitaxel 20 mg/m\^2: Cabazitaxel 25 mg/m\^2) and stratified according to Eastern Cooperative Oncology Group Performance Status (ECOG PS) score (0 or 1 versus 2), measurability of disease (measurable versus non-measurable) and region.

Participant milestones

Participant milestones
Measure	Cabazitaxel 20 mg/m^2 Cabazitaxel 20 mg/m\^2 intravenous (IV) infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until disease progression (DP), unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Overall Study STARTED	598	602
Overall Study Treated	587	588
Overall Study COMPLETED	586	595
Overall Study NOT COMPLETED	12	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Cabazitaxel 20 mg/m^2 Cabazitaxel 20 mg/m\^2 intravenous (IV) infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until disease progression (DP), unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Overall Study Lost to Follow-up	12	7

Baseline Characteristics

Cabazitaxel at 20 mg/m² Compared to 25 mg/m² With Prednisone for the Treatment of Metastatic Castration Resistant Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cabazitaxel 20 mg/m^2 n=598 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=602 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Total n=1200 Participants Total of all reporting groups
Age, Customized <65 years	182 participants n=5 Participants	180 participants n=7 Participants	362 participants n=5 Participants
Age, Customized 65 to 74 years	296 participants n=5 Participants	295 participants n=7 Participants	591 participants n=5 Participants
Age, Customized ≥75 years	120 participants n=5 Participants	127 participants n=7 Participants	247 participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	598 Participants n=5 Participants	602 Participants n=7 Participants	1200 Participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline up to death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)

Population: Analysis was performed on Intent-to-Treat (ITT) population, which included all randomized participants.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=598 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=602 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Overall Survival (OS)	13.4 months Interval 12.19 to 14.88	14.5 months Interval 13.47 to 15.28

SECONDARY outcome

Timeframe: From baseline up to tumor progression, PSA progression, pain progression, death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)

Population: Analysis was performed on ITT population.

PFS was evaluated from date of randomization to date of first documentation of any of the events: 1) Radiological tumor progression: as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1: at least a 20% increase in sum of diameters of target lesions (sum must also demonstrate an absolute increase of ≥5 mm) taking as reference the smallest sum while on study, appearance of one or more new lesions, or unequivocal progression of existing non target lesions, 2) Prostate Specific Antigen (PSA) progression: ≥25% increase over baseline/nadir value if baseline PSA ≥10 ng/mL; or 25% increase above the baseline level if baseline PSA \>0 ng/mL \& \<10 ng/mL; or post-baseline value of \>=2 ng/mL, if baseline PSA=0 ng/mL, 3) Pain progression: increase of ≥1 point in median Present Pain Intensity (PPI) from nadir or ≥25% increase in mean analgesic score (AS) from baseline score or requirement of local palliative radiotherapy, 4) Death. Analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=598 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=602 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Progression Free Survival (PFS)	2.9 months Interval 2.79 to 3.45	3.5 months Interval 3.12 to 3.94

SECONDARY outcome

Timeframe: From baseline up to tumor progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)

Population: Analysis was performed on ITT population.

Time to Tumor progression was defined as the first occurrence of radiological tumor progression according to RECIST 1.1. Radiological tumor progression was defined at least a 20% increase in sum of diameters of target lesions (sum must also demonstrate an absolute increase of ≥5 mm) taking as reference the smallest sum while on study, appearance of one or more new lesions, or unequivocal progression of existing non target-lesions. Analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=598 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=602 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Time to Tumor Progression	9.0 months Interval 8.38 to 9.79	9.3 months Interval 8.61 to 9.92

SECONDARY outcome

Timeframe: From baseline up to DP or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)

Population: Analysis was performed on ITT population. Number of participants analyzed= participants evaluable for tumor response with measurable disease at baseline and at least one valid post-baseline value.

Overall objective tumor response was defined as either a partial response (PR) or complete response (CR) according to the RECIST 1.1 criteria, as assessed by the investigator. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=271 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=256 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Percentage of Participants With Overall Objective Tumor Response	18.5 percentage of participants Interval 13.8 to 23.1	23.4 percentage of participants Interval 18.2 to 28.6

SECONDARY outcome

Timeframe: From baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)

Population: Analysis was performed on ITT population.

Time to PSA progression was time interval between randomization \& first occurrence of PSA progression. PSA progression defined as: 1) PSA responders (\>50% decline from baseline PSA ≥10 ng/mL): increase of ≥25% (≥2 ng/mL) over nadir value, confirmed by second PSA ≥3 weeks later; 2) PSA non-responders (did not achieve \>50% decline from baseline PSA ≥10 ng/mL): increase of ≥25% (≥2 ng/mL) over baseline value, confirmed by second PSA ≥3 weeks later; 3) In participants not eligible for PSA response (baseline PSA \<10 ng/mL): (a) participants with baseline PSA \>0 ng/mL \& \<10 ng/mL: increase in PSA by 25% (≥2 ng/mL) above baseline level, confirmed by second PSA value ≥3 weeks apart; (b) participants with baseline value=0 ng/mL: post-baseline PSA value ≥2 ng/mL. Note (for 1-3): Rise in PSA in first 12 weeks was progression only if met definition above and was associated with other sign of DP or if it continued beyond 12 weeks. Analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=598 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=602 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Time to PSA Progression	5.7 months Interval 4.96 to 6.47	6.8 months Interval 6.11 to 7.46

SECONDARY outcome

Timeframe: From baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months)

Population: Analysis was performed on ITT population. Number of participants analyzed= participants evaluable for PSA response with PSA value ≥10 ng/mL at baseline and at least one valid post-baseline value.

PSA response was defined as ≥50% decrease from baseline in serum PSA levels, confirmed by a second PSA value at least 3 weeks later in participants with baseline PSA value ≥10 ng/mL.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=543 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=538 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Percentage of Participants With PSA Response	29.5 percentage of participants Interval 25.6 to 33.3	42.9 percentage of participants Interval 38.8 to 47.1

SECONDARY outcome

Timeframe: From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months)

Population: Analysis was performed on ITT population.

Pain Progression was defined as an increase of ≥1 point in the median PPI from its nadir confirmed by a second assessment at least 3 weeks later or ≥25 % increase in the mean AS compared with the baseline score confirmed by a second assessment at least 3 weeks later or requirement for local palliative radiotherapy. PPI was rated by participant in a diary using a scale of 0=no pain, 1=mild, 2=discomforting, 3=distressing, 4=horrible 5=excruciating. Analgesic use was recorded by the participant in a diary. AS was calculated from the analgesic use data based on a table of analgesic medications, with non-narcotic medications assigned a value of 1 point and narcotic medications assigned a value of 4 points. Analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=598 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=602 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Time to Pain Progression	6.2 months Interval 5.22 to 7.39	6.4 months Interval 5.55 to 7.26

SECONDARY outcome

Timeframe: From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months)

Population: Analysis was performed on ITT population. Number of participants analyzed= participants evaluable for pain response with pain score with median PPI ≥2 and/or mean AS ≥10 points at baseline and at least one valid post-baseline value.

Pain response was defined as either a ≥2-point decrease from baseline median PPI score without increase in AS, or a ≥50% decrease from baseline mean AS without increase in the PPI score, maintained for 2 consecutive evaluations at least 3 weeks apart. Increases in pain during the first 12 weeks were ignored in determining pain response.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=248 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=284 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Percentage of Participants With Pain Response	34.7 percentage of participants Interval 28.8 to 40.6	37.3 percentage of participants Interval 31.7 to 42.9

SECONDARY outcome

Timeframe: Baseline, Day 1 of each Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 (each cycle 21-day); post-treatment follow up 1 (up to 12 weeks)

Population: FACT-P population included randomized participants who completed FACT-P questionnaire at baseline \& in at least one post-baseline assessment. Number of participants analyzed=participants with evaluable FACT-P TOI for specified outcome measure. Here, 'n' signifies number of participants with available data for specified category.

FACT-P is a 39-item participant questionnaire that measures the concerns of participants with prostate cancer. It consists of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate-specific concerns (12 items). FACT-P TOI combines physical well-being, functional well-being, and prostate-specific concerns sub-scales for a total possible score range of 0 to 104, where higher values represent better HRQoL.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=521 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=494 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of Health Related Quality of Life (HRQoL) Change from baseline at cycle 1 (n =521, 494)	4.69 units on a scale Interval 2.95 to 6.44	5.08 units on a scale Interval 3.32 to 6.84
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of Health Related Quality of Life (HRQoL) Change from baseline at cycle 2 (n = 500, 494)	4.4 units on a scale Interval 2.67 to 6.14	5.55 units on a scale Interval 3.81 to 7.3
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of Health Related Quality of Life (HRQoL) Change from baseline at cycle 3 (n =456, 451)	3.75 units on a scale Interval 2.0 to 5.5	5.46 units on a scale Interval 3.7 to 7.23
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of Health Related Quality of Life (HRQoL) Change from baseline at cycle 4 (n =420, 415)	2.57 units on a scale Interval 0.8 to 4.33	3.82 units on a scale Interval 2.04 to 5.6
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of Health Related Quality of Life (HRQoL) Change from baseline at cycle 5 (n =339, 361)	1.78 units on a scale Interval -0.03 to 3.59	3.06 units on a scale Interval 1.26 to 4.87
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of Health Related Quality of Life (HRQoL) Change from baseline at cycle 6 (n =275, 318)	2.57 units on a scale Interval 0.72 to 4.43	2.03 units on a scale Interval 0.2 to 3.86
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of Health Related Quality of Life (HRQoL) Change from baseline at cycle 7 (n =225, 262)	2.51 units on a scale Interval 0.6 to 4.42	2.73 units on a scale Interval 0.85 to 4.6
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of Health Related Quality of Life (HRQoL) Change from baseline at cycle 8 (n =196, 227)	1.44 units on a scale Interval -0.5 to 3.39	2.08 units on a scale Interval 0.16 to 3.99
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of Health Related Quality of Life (HRQoL) Change from baseline at cycle 9 (n =165, 172)	0.94 units on a scale Interval -1.06 to 2.94	1.46 units on a scale Interval -0.55 to 3.46
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of Health Related Quality of Life (HRQoL) Change from baseline at cycle 10 (n =137, 141)	0.02 units on a scale Interval -2.05 to 2.1	1.31 units on a scale Interval -0.76 to 3.39
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of Health Related Quality of Life (HRQoL) Change from baseline at Follow-up 1 (n =136, 152)	-2.27 units on a scale Interval -4.35 to -0.19	-1.16 units on a scale Interval -3.21 to 0.88

SECONDARY outcome

Timeframe: Baseline, Day 1 of each Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 (each cycle 21-day); post-treatment follow up 1 (up to 12 weeks)

Population: Analysis was performed on FACT-P population. Number of participants analyzed=participants with evaluable FACT-P Total Score for specified outcome measure. Here, 'n' signifies number of participants with available data for specified category.

FACT-P is a 39-item participant questionnaire that measures the concerns of participants with prostate cancer. It consists of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate-specific concerns (12 items). FACT-P Total Score sums all 5 sub-scales to give a score in the range of 0 to 156, where higher values represent better HRQoL.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=521 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=495 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Change From Baseline in FACT-P:Total Score as a Measure of HRQoL Change from baseline at cycle 1 (n =521, 495)	5.6 units on a scale Interval 3.43 to 7.78	5.75 units on a scale Interval 3.55 to 7.95
Change From Baseline in FACT-P:Total Score as a Measure of HRQoL Change from baseline at cycle 2 (n = 502, 492)	5.39 units on a scale Interval 3.23 to 7.55	6.23 units on a scale Interval 4.05 to 8.42
Change From Baseline in FACT-P:Total Score as a Measure of HRQoL Change from baseline at cycle 3 (n = 459, 452)	4.39 units on a scale Interval 2.21 to 6.57	6.09 units on a scale Interval 3.89 to 8.3
Change From Baseline in FACT-P:Total Score as a Measure of HRQoL Change from baseline at cycle 4 (n = 421, 415)	2.94 units on a scale Interval 0.73 to 5.14	4.2 units on a scale Interval 1.98 to 6.42
Change From Baseline in FACT-P:Total Score as a Measure of HRQoL Change from baseline at cycle 5 (n = 339, 365)	1.79 units on a scale Interval -0.46 to 4.04	3.33 units on a scale Interval 1.08 to 5.59
Change From Baseline in FACT-P:Total Score as a Measure of HRQoL Change from baseline at cycle 6 (n = 275, 320)	2.57 units on a scale Interval 0.26 to 4.88	2.35 units on a scale Interval 0.06 to 4.64
Change From Baseline in FACT-P:Total Score as a Measure of HRQoL Change from baseline at cycle 7 (n = 229, 267)	2.62 units on a scale Interval 0.25 to 4.99	2.72 units on a scale Interval 0.38 to 5.06
Change From Baseline in FACT-P:Total Score as a Measure of HRQoL Change from baseline at cycle 8 (n = 196, 226)	1.35 units on a scale Interval -1.08 to 3.78	1.98 units on a scale Interval -0.42 to 4.37
Change From Baseline in FACT-P:Total Score as a Measure of HRQoL Change from baseline at cycle 9 (n = 164, 172)	1.1 units on a scale Interval -1.4 to 3.6	1 units on a scale Interval -1.5 to 3.51
Change From Baseline in FACT-P:Total Score as a Measure of HRQoL Change from baseline at cycle 10 (n = 137, 141)	0.02 units on a scale Interval -2.57 to 2.61	1.33 units on a scale Interval -1.26 to 3.93
Change From Baseline in FACT-P:Total Score as a Measure of HRQoL Change from baseline at Follow-up 1 (n = 137, 153)	-3.1 units on a scale Interval -5.69 to -0.51	-2.09 units on a scale Interval -4.65 to 0.46

SECONDARY outcome

Timeframe: From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months)

Population: Analysis was performed on FACT-P population. Number of participants analyzed= participants with evaluable FACT-P total score for specified outcome measure.

FACT-P is a 39-item participant questionnaire that measures the concerns of participants with prostate cancer. It consists of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate-specific concerns (12 items). FACT-P Total Score sums all 5 sub-scales to give a score in the range of 0 to 156, where higher values represent better HRQoL. Responder of FACT-P was defined as at least one occurrence of 7-point improvement from baseline in FACT-P total score during treatment period.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=540 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=525 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Percentage of Participants With FACT-P Total Score Response	57.2 percentage of participants Interval 53.0 to 61.4	59.4 percentage of participants Interval 55.2 to 63.6

SECONDARY outcome

Timeframe: From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months)

Population: Analysis was performed on FACT-P population.

The time to definitive deterioration (10% decrease in score from baseline) was assessed for the individual sub-scales (Physical Well-Being; Social/Family Well-Being; Emotional Well-Being; Functional Well-Being; Prostate-Specific Concerns). Analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=557 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=543 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Time to Definitive Deterioration of Score by 10% From Baseline on FACT-P Sub-Scales Physical well-being	6.6 months Interval 5.85 to 7.82	8.3 months Interval 7.16 to 8.74
Time to Definitive Deterioration of Score by 10% From Baseline on FACT-P Sub-Scales Social/family well-being	10.8 months Interval 9.26 to 13.37	12.4 months Interval 8.97 to 13.83
Time to Definitive Deterioration of Score by 10% From Baseline on FACT-P Sub-Scales Emotional well-being	9.7 months Interval 7.36 to 11.3	9.9 months Interval 8.54 to 12.52
Time to Definitive Deterioration of Score by 10% From Baseline on FACT-P Sub-Scales Functional well-being	6.6 months Interval 5.55 to 7.43	6.7 months Interval 6.01 to 8.34
Time to Definitive Deterioration of Score by 10% From Baseline on FACT-P Sub-Scales Prostate specific concern	8.7 months Interval 7.62 to 9.66	9.7 months Interval 8.77 to 10.87

SECONDARY outcome

Timeframe: From baseline until death or study cut-off date (maximum duration: 48 months)

Population: Analysis was performed on ITT population.

The ECOG PS was used to evaluate participant's DP and the effect of the disease on the participant's activities of daily living. It ranges on the scale from 0-5 (0= normal activity; 1= symptoms but ambulatory; 2= in bed for \< 50 % of the time; 3= in bed for \> 50% of the time; 4= 100% bedridden; 5= dead). Time to definitive deterioration in ECOG PS score from baseline was defined as a change from 0, 1 to ≥2, or from 2 to ≥3. Analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=598 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=602 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Time to Definitive Deterioration of ECOG PS Score From Baseline	14.9 months Interval 11.43 to 23.59	14.1 months Interval 12.22 to 20.17

SECONDARY outcome

Timeframe: From baseline until death or study cut-off date (maximum duration: 48 months)

Population: Analysis was performed on ITT population.

Time to definitive weight loss was defined as the time to first occurrence of ≥5% or ≥10% decrease in body weight from baseline. Analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=598 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=602 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Time to Definitive Weight Loss by 5% and 10% From Baseline Weight Loss by 5%	10.6 months Interval 9.26 to 13.17	11.1 months Interval 10.12 to 12.42
Time to Definitive Weight Loss by 5% and 10% From Baseline Weight Loss by 10%	NA months Interval 12.65 to The median and upper bound of the confidence interval could not be calculated using the Kaplan-Meier method	20.3 months Interval 14.23 to The upper bound of the confidence interval could not be calculated using the Kaplan-Meier method

SECONDARY outcome

Timeframe: From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months)

Population: Analysis was performed on ITT population.

Concomitant medications used were recorded for all participants, and time of first definitive consumption of narcotic medication (if it occurred) was determined. This measure summarizes the time from baseline to first definitive consumption of narcotic medication. Analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=598 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=602 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Time to First Definitive Consumption of Narcotic Medication	2.2 months Interval 0.99 to 3.65	0.8 months Interval 0.3 to 2.2

SECONDARY outcome

Timeframe: From first administration of study treatment until 30 days after the last administration of study treatment (Maximum duration: 48 months)

Population: Safety population included all randomized participants who received at least one dose of the study drug during study treatment period.

Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an adverse event (AE) without regard to possibility of causal relationship with this treatment. TEAEs: AEs that developed or worsened or became serious during on-treatment period. On-treatment period: The time from the first dose of treatment to 30 days after the last dose of treatment (either Cabazitaxel or Prednisone). A serious adverse event: Any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. National Cancer Institute Common Terminology Criteria (NCI-CTCAE) version 4.03 (Grade 3 \[severe\] and Grade 4 \[life-threatening\]) was used in this study to grade clinical AEs.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=580 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=595 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Any Grade TEAE	91.2 percentage of participants	93.9 percentage of participants
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Any Grade 3-4 TEAE	39.7 percentage of participants	54.5 percentage of participants
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Grade 3-4 TEAE excluding laboratory TEAE	35.7 percentage of participants	48.1 percentage of participants
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Grade 3-4 TEAE excluding DP TEAEs	39.0 percentage of participants	53.9 percentage of participants
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Grade 3-4 TEAE excluding laboratory and DP TEAEs	35.0 percentage of participants	47.4 percentage of participants
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Any Serious TEAE	30.5 percentage of participants	43.2 percentage of participants
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Any TEAE leading to permanent discontinuation	16.4 percentage of participants	19.5 percentage of participants

SECONDARY outcome

Timeframe: Day 1 of Cycle 1: 5 minutes before the end of infusion (EOI), 15 minutes, 1 to 4 hour, 6 to 24 hours, 48 to 168 hour after EOI

Population: Analysis was performed on PK population that included participants who had evaluable PK data. Number of participants analyzed= participants with PK assessment at specified time-points.

Blood samples for pharmacokinetic (PK) analysis were obtained from a subset of the study participants (approximately 150 participants/group, by protocol) according to a sparse sampling strategy.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=133 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=166 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Plasma Clearance (CL) for Cabazitaxel	44.832 Litre/hour Standard Deviation 15.075	49.662 Litre/hour Standard Deviation 17.613

SECONDARY outcome

Timeframe: Day 1 of Cycle 1: 5 minutes before the EOI, 15 minutes, 1 to 4 hour, 6 to 24 hours, 48 to 168 hour after EOI

Population: Analysis was performed on PK population. Number of participants analyzed= participants with PK assessment at specified time-points.

Blood samples for PK analysis were obtained from a subset of the study participants (approximately 150 participants/group, by protocol) according to a sparse sampling strategy.

Outcome measures

Outcome measures
Measure	Cabazitaxel 20 mg/m^2 n=133 Participants Cabazitaxel 20 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.	Cabazitaxel 25 mg/m^2 n=166 Participants Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
Plasma Steady State Volume of Distribution (Vss) for Cabazitaxel	7381.46 litre Standard Deviation 4488.72	7040.10 litre Standard Deviation 5133.12

Adverse Events

Cabazitaxel 20 mg/m^2

Serious events: 177 serious events

Other events: 450 other events

Deaths: 0 deaths

Cabazitaxel 25 mg/m^2

Serious events: 257 serious events

Other events: 507 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