Cabazitaxel Versus the Switch to Alternative AR-targeted Agent (Enzalutamide or Abiraterone) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients Previously Treated With Docetaxel and Who Rapidly Failed a Prior AR-targeted Agent (CARD)

• ClinicalTrials.gov Identifier: NCT02485691
• Recruitment Status: Completed
• First Posted: June 30, 2015
• Results First Posted: February 14, 2022
• Last Update Posted: May 27, 2022
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer Metastatic
• Interventions: Drug: cabazitaxel XRP6258; Drug: enzalutamide; Drug: abiraterone acetate; Drug: prednisone
• Enrollment: 255

Participant Flow

Recruitment Details	The study was conducted at 66 active centers in 13 countries. A total of 255 participants were randomized between 09 November 2015 to 13 November 2018, out of which 250 participants received treatment with the study drug.
Pre-assignment Details	Participants were randomized to receive either cabazitaxel or Androgen receptor (AR) targeted therapy (abiraterone or enzalutamide were assigned based on previous AR targeted treatment in which participants previously treated with abiraterone were treated with enzalutamide and vice versa due to resistance).

Arm/Group Title	Cabazitaxel	Abiraterone Acetate or Enzalutamide
Arm/Group Description	Participants received Cabazitaxel 25 mg/m^2 intravenous (IV) infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic granulocyte-colony stimulating factor (G-CSF) as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration =12.5 weeks)
Period Title: Overall Study
Started	129	126
Treated	126	124
Completed	0	0
Not Completed	129	126
Reason Not Completed
Adverse Event	25	11
Poor compliance to protocol	0	1
Disease progression	57	92
Investigator's decision	23	5
Participant's request	13	6
Other reason	8	9
Randomized and not treated	3	2

Baseline Characteristics

Arm/Group Title		Cabazitaxel	Abiraterone Acetate or Enzalutamide	Total
Arm/Group Description		Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).	Total of all reporting groups
Overall Number of Baseline Participants		129	126	255
Baseline Analysis Population Description		Analysis was performed on Intent-to-treat (ITT) population, that included any participant who had been allocated to a randomized treatment regardless of whether the treatment kit was used, analyzed according to the treatment group allocated by randomization.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	129 participants	126 participants	255 participants
		69.7 (8.3)	69.7 (7.9)	69.7 (8.1)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	129 participants	126 participants	255 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	129 100.0%	126 100.0%	255 100.0%
Race and Ethnicity Not Collected [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	0 participants	0 participants	0 participants
				0
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.

Outcome Measures

1. Primary Outcome

Title	Radiographic Progression-Free Survival (rPFS)
Description	Radiographic progression-free survival: time (in months) from randomization to occurrence of any one of following: radiological tumor progressions using response evaluation criteria in solid tumors (RECIST 1.1), progression of bone lesions using Prostate Cancer Working Group 2 (PCWG2) criteria or occurrence of death due to any cause. Progression as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Progression of bone lesions (PCWG2 criteria): first bone scan with >= 2 new lesions compared to Baseline observed less than (<) 12 weeks from randomization and confirmed by a second bone scan performed >=6 weeks; first bone scan with >=2 new lesions compared to Baseline observed >=12 weeks from randomization. In accordance with protocol, data cut-off date for final analysis of this endpoint was the date when 196 rPFS events had occurred. Analysis done by Kaplan-Meier method.
Time Frame	From randomization until tumor progression or bone lesion progression, death due to any cause, or data cut-off date whichever comes first (maximum duration: up to 141 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Cabazitaxel	Abiraterone Acetate or Enzalutamide
Arm/Group Description:	Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
Overall Number of Participants Analyzed	129	126
Median (95% Confidence Interval); Unit of Measure: months
	8.0; (5.7 to 9.2)	3.7; (2.8 to 5.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cabazitaxel, Abiraterone Acetate or Enzalutamide
	Comments	Hazard ratio was estimated using a Cox Proportional Hazards regression model. The Cox proportional hazard model was stratified by ECOG performance status, time from AR- targeted agent initiation progression, timing of AR targeted agent as specified at the time of randomization.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measure are reported and continued when previous outcome measure was statistically significant at two-sided 0.05. Only the primary and the first 4 secondary outcome measures were included in the procedure.
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	P-value from 2-sided stratified log-rank test, stratified for ECOG performance status, time from AR- targeted agent initiation progression, timing of AR targeted agent as specified at the time of randomization. Significance threshold was at 0.05.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95%; 0.40 to 0.73
	Estimation Comments	Cabazitaxel vs Abiraterone Acetate or Enzalutamide

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival was defined as the time interval (in months) from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date participant was known to be alive, or at the cut-off date whichever comes first. Analysis was performed by Kaplan-Meier method.
Time Frame	From randomization to death due to any cause, or data cut-off date whichever comes first (maximum duration: up to 141 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Cabazitaxel	Abiraterone Acetate or Enzalutamide
Arm/Group Description:	Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
Overall Number of Participants Analyzed	129	126
Median (95% Confidence Interval); Unit of Measure: months
	13.6; (11.5 to 17.5)	11.0; (9.2 to 12.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cabazitaxel, Abiraterone Acetate or Enzalutamide
	Comments	Hazard ratio was estimated using a Cox Proportional Hazards regression model. The Cox proportional hazard model was stratified by ECOG performance status, time from AR- targeted agent initiation progression, timing of AR targeted agent as specified at the time of randomization.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measure are reported and continued when previous outcome measure was statistically significant at two-sided 0.05. Only the primary and the first 4 secondary outcome measures were included in the procedure.
Statistical Test of Hypothesis	P-Value	0.0078
	Comments	P-value from two-sided stratified log-rank test, stratified for ECOG performance status, time from AR-targeted agent initiation to progression, timing of AR-targeted agent as specified at the time of randomization. Significance threshold = 0.05.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95%; 0.46 to 0.89
	Estimation Comments	Cabazitaxel vs Abiraterone Acetate or Enzalutamide

3. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS:time duration (in months) from date of randomization to date of first occurrence of any of following events: radiological tumor progression (RECIST 1.1); progression of bone lesions (PCWG2); symptomatic progression (developing urinary or bowel symptoms; need to change anti-cancer therapy), pain progression or death due to any cause. Tumor Progression(RECIST 1.1): at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Progression of bone lesion (PCWG2 criteria): first bone scan with >=2 new lesions compared to Baseline and confirmed by second bone scan performed >=6 weeks later; pain progression: increase by >=30% from Baseline in pain intensity score (calculated using scale ranged from 0=no pain to 5=extreme pain) or increase in analgesic usage score >=30% (calculated from analgesic use data, non-narcotic medications assigned value of 1 point and narcotic medications assigned 4 points). Analyzed by Kaplan-Meier method.
Time Frame	From randomization until tumor progression or bone lesion progression, pain progression, death due to any cause, or data cut-off date whichever comes first (maximum duration: up to 141 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Cabazitaxel	Abiraterone Acetate or Enzalutamide
Arm/Group Description:	Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
Overall Number of Participants Analyzed	129	126
Median (95% Confidence Interval); Unit of Measure: months
	4.4; (3.6 to 5.4)	2.7; (2.3 to 2.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cabazitaxel, Abiraterone Acetate or Enzalutamide
	Comments	Hazard ratio was estimated using a Cox Proportional Hazards regression model. The Cox proportional hazard model was stratified by ECOG performance status, time from AR- targeted agent initiation progression, timing of AR targeted agent as specified at the time of randomization.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measure are reported and continued when previous outcome measure was statistically significant at two-sided 0.05. Only the primary and the first 4 secondary outcome measures were included in the procedure.
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	P-value from two-sided stratified log-rank test, stratified for ECOG performance status, time from AR-targeted agent initiation to progression, timing of AR-targeted agent as specified at the time of randomization. Significance threshold = 0.05.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.52
	Confidence Interval	(2-Sided) 95%; 0.40 to 0.68
	Estimation Comments	Cabazitaxel vs Abiraterone Acetate or Enzalutamide

4. Secondary Outcome

Title	Percentage of Participants With Prostate Specific Antigen (PSA) Response
Description	PSA response was defined as >= 50% decrease from baseline in serum PSA levels, confirmed by a second PSA value at least 3 weeks later.
Time Frame	Baseline up to PSA response, death due to any cause or data cut-off date whichever comes first (maximum duration: up to 141 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on subset of ITT population (any participant who had been allocated to a randomized treatment, analyzed according to group allocated) with PSA level >2 ng/mL at baseline, and with at least two post-baseline assessments before any further anti-cancer therapy for specified outcome measure.

Arm/Group Title	Cabazitaxel	Abiraterone Acetate or Enzalutamide
Arm/Group Description:	Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
Overall Number of Participants Analyzed	113	105
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	36.3; (27.4 to 45.1)	14.3; (7.6 to 21.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cabazitaxel, Abiraterone Acetate or Enzalutamide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measure are reported and continued when previous outcome measure was statistically significant at two-sided 0.05. Only the primary and the first 4 secondary outcome measures were included in the procedure.
Statistical Test of Hypothesis	P-Value	0.0003
	Comments	Cochran-Mantel-Haenszel test stratified by ECOG performance status, time from AR-targeted agent initiation to progression, timing of AR-targeted agent as specified at the time of randomization. Significance threshold = 0.05.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

5. Secondary Outcome

Title	Percentage of Participants With Overall Objective Tumor Response
Description	Overall objective tumor response was defined as having a partial response (PR) or complete response (CR) according to the RECIST version 1.1. 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 have 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.
Time Frame	From randomization until disease progression, death due to any cause or data cut-off date whichever comes first (maximum duration: up to 141 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on subset of ITT population (any participant who had been allocated to a randomized treatment, analyzed according to group allocated) with measurable disease at baseline and at least one post-baseline assessment before any further anti-cancer therapy for specified outcome measure.

Arm/Group Title	Cabazitaxel	Abiraterone Acetate or Enzalutamide
Arm/Group Description:	Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
Overall Number of Participants Analyzed	63	52
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	36.5; (24.6 to 48.4)	11.5; (2.9 to 20.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cabazitaxel, Abiraterone Acetate or Enzalutamide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measure are reported and continued when previous outcome measure was statistically significant at two-sided 0.05. Only the primary and the first 4 secondary outcome measures were included in the procedure.
Statistical Test of Hypothesis	P-Value	0.0004
	Comments	Cochran-Mantel-Haenszel test stratified by ECOG performance status, time from AR-targeted agent initiation to progression, timing of AR-targeted agent as specified at the time of randomization. Significance threshold = 0.05.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

6. Secondary Outcome

Title	Time to PSA Progression (TTPP)
Description	TTPP was defined as the time duration (in months) between the date of randomization and the date of first documented PSA progression. PSA progression (as per PCWG 2) was defined as: 1) If decline from Baseline value: an increase of >=25% (at least 2 ng/mL) over the nadir value, confirmed by a second PSA value at least 3 weeks apart; 2) If no decline from Baseline value: an increase of >=25% (at least 2 ng/mL) over the baseline value after 12 weeks of treatment, confirmed by a second PSA value at least 3 weeks apart. Analysis performed by Kaplan-Meier method.
Time Frame	From time from randomization until PSA progression, death due to any cause or data cut-off whichever comes first (maximum duration: up to 141 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on subset of ITT population (any participant who had been allocated to a randomized treatment, analyzed according to group allocated) with PSA level > 2ng/mL at baseline, and with at least two post-baseline assessments before any further anti-cancer therapy for specified outcome measure.

Arm/Group Title	Cabazitaxel	Abiraterone Acetate or Enzalutamide
Arm/Group Description:	Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
Overall Number of Participants Analyzed	113	105
Median (95% Confidence Interval); Unit of Measure: months
	6.3; (4.2 to 8.3)	2.1; (1.7 to 2.3)

7. Secondary Outcome

Title	Duration of Tumor Response
Description	Duration of tumor response was defined as the time (in months) from date of first response (CR or PR) until date of first documentation of tumor progression or death, whichever occurs first. As per RECIST 1.1 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 have 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. Progression was defined as at least a 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.
Time Frame	From the date of the first response to the date of first documented tumor progression, or death due to any cause or data cut-off date whichever comes first (maximum duration: up to 141 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on subset of participants with overall objective tumor response.

Arm/Group Title	Cabazitaxel	Abiraterone Acetate or Enzalutamide
Arm/Group Description:	Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
Overall Number of Participants Analyzed	23	6
Median (95% Confidence Interval); Unit of Measure: months
	6.5; (5.6 to 11.4)	8.0 [1]; (1.1 to NA)

[1]

Upper limit of Confidence Interval (CI) was not estimable due to less number of participants with overall objective tumor response.

8. Secondary Outcome

Title	Percentage of Participants Achieving Pain Response Assessed Using Brief Pain Inventory-Short Form (BPI-SF) Pain Intensity Score
Description	Pain response as per BPI-SF was defined as a decrease of at least 30% from Baseline in the average of BPI-SF pain intensity score observed at 2 consecutive evaluations >=3 weeks apart without increase in analgesic usage score (calculated from analgesic use data, with non-narcotic medications assigned value of 1 point and narcotic medications assigned 4 points). The BPI-SF is a self-administered questionnaire developed to assess the severity of pain on a 0-10 categorical scale where 0=no pain, 10=pain as bad as you can imagine. Higher scores indicated worst outcomes. Percentage of Participants Achieving Pain Response assessed using BPI-SF Pain Intensity Score were reported.
Time Frame	Baseline until pain progression, first further anticancer therapy, or data cut-off whichever comes first (maximum duration: up to 141 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on subset of ITT population (any participant who had been allocated to a randomized treatment, analyzed according to group allocated) with baseline assessment and at least one post-baseline assessment before any further anti-cancer therapy for specified outcome measure.

Arm/Group Title	Cabazitaxel	Abiraterone Acetate or Enzalutamide
Arm/Group Description:	Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
Overall Number of Participants Analyzed	111	109
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	45.9; (36.7 to 55.2)	19.3; (11.9 to 26.7)

9. Secondary Outcome

Title	Time to Pain Progression
Description	Time to pain progression was defined as the time duration (in months) between the date of randomization and the date of first documented pain progression. Pain progression, in participants with no pain or stable pain at Baseline was defined as increase of >=30% from baseline in the BPI-SF pain intensity score observed at 2 consecutive evaluations >=3 weeks apart without decrease in analgesic usage score or increase in analgesic usage score (calculated from analgesic use data, with non-narcotic medications assigned value of 1 point and narcotic medications assigned 4 points) >=30%. The BPI-SF is a self-administered questionnaire developed to assess the severity of pain on a 0-10 categorical scale where 0=no pain, 10=pain as bad as you can imagine. Higher scores indicated worst outcomes. Analysis was performed by Kaplan-Meier method.
Time Frame	Baseline until pain progression or data cut-off whichever comes first (maximum duration: up to 141 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on subset of ITT population (any participant who had been allocated to a randomized treatment, analyzed according to group allocated) with baseline assessment and at least one post-baseline assessment before any further anti-cancer therapy for BPI-SF pain intensity score.

Arm/Group Title	Cabazitaxel	Abiraterone Acetate or Enzalutamide
Arm/Group Description:	Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
Overall Number of Participants Analyzed	111	109
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	8.5 [2]; (4.9 to NA)

[1]

Median, lower and upper limit of CI was not estimable because the curve's upper CI bound had not crossed 50% survival threshold.

[2]

Upper limit of CI was not estimable because the curve's upper bound CI had not crossed 50% survival threshold.

10. Secondary Outcome

Title	Number of Symptomatic Skeletal Events (SSE)
Description	SSE was defined as occurrence of a new symptomatic pathological fracture, use of external beam radiation to relieve bone pain, occurrence of spinal cord compression or tumor- related orthopedic surgical intervention.
Time Frame	Baseline until occurrence of first SSE or data cut-off, whichever comes first (maximum duration: up to 141 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Cabazitaxel	Abiraterone Acetate or Enzalutamide
Arm/Group Description:	Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
Overall Number of Participants Analyzed	129	126
Measure Type: Number; Unit of Measure: events
	24	35

11. Secondary Outcome

Title	Time to Symptomatic Skeletal Event
Description	Time to SSE was defined as the time duration (in months) between the date of randomization and the date of occurrence of the first SSE. Analysis was performed by Kaplan-Meier method.
Time Frame	From date of randomization until first SSE, or data cut-off whichever comes first (maximum duration: up to 141 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Cabazitaxel	Abiraterone Acetate or Enzalutamide
Arm/Group Description:	Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
Overall Number of Participants Analyzed	129	126
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (20.0 to NA)	16.7 [2]; (10.8 to NA)

[1]

Median and upper limit of CI was not estimable because of low number of participants with events.

[2]

Upper limit of CI was not estimable because of low number of participants with events.

12. Secondary Outcome

Title	Health-Related Quality of Life (HRQOL): Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score at Cycle 2, 3, 4, 5, 6, 7, 8 and End of Treatment
Description	Health-related quality of life (HRQOL) evaluation was performed using the FACT-P questionnaire (Version 4). FACT-P was a 39-item participant rated questionnaire that measures the concerns of participants with prostate cancer. It consisted 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 was the sum of all 5 subscale scores. It ranged from 0 to156 with higher score indicated better quality of life with fewer symptoms. Baseline corresponded to last evaluable assessment before treatment administration.
Time Frame	Baseline, Day 1 of each Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 6, Cycle 7, Cycle 8 and at End of Treatment (any time up to 141 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on HRQOL population which included participants who received at least one dose of the study drug and with an evaluable FACT-P questionnaire at baseline and at least one post-baseline evaluable FACT-P. Here 'Number analyzed' signifies participants with available data for each specified category.

Arm/Group Title		Cabazitaxel	Abiraterone Acetate or Enzalutamide
Arm/Group Description:		Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
Overall Number of Participants Analyzed		108	114
Mean (Standard Deviation); Unit of Measure: score on a scale
Cycle 2	Number Analyzed	104 participants	106 participants
		2.6 (12.3)	-0.0 (12.4)
Cycle 3	Number Analyzed	99 participants	94 participants
		2.7 (16.1)	-1.0 (16.8)
Cycle 4	Number Analyzed	93 participants	77 participants
		2.8 (14.8)	-0.7 (16.8)
Cycle 5	Number Analyzed	79 participants	56 participants
		2.1 (17.9)	-1.0 (16.1)
Cycle 6	Number Analyzed	64 participants	39 participants
		-3.7 (18.0)	0.4 (18.6)
Cycle 7	Number Analyzed	58 participants	33 participants
		-2.2 (19.3)	2.7 (19.9)
Cycle 8	Number Analyzed	47 participants	25 participants
		-4.8 (20.4)	0.8 (23.0)
End of treatment	Number Analyzed	51 participants	31 participants
		-6.3 (16.1)	-7.5 (15.7)

13. Secondary Outcome

Title	Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Utility Single Index and Visual Analogue Scale (VAS) Scores at Cycle 2, 3, 4, 5, 6, 7, 8 and End of Treatment
Description	EQ-5D was a standardized HRQOL questionnaire consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). EQ-5D descriptive system comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression measured on 3 levels (no problem, some problems & severe problems) within a particular EQ-5D dimension. 5 dimensional 3-level system was converted into single index utility score. Possible values for single index utility score ranged from -0.594 (severe problems in all dimensions) to 1.0 (no problem in all dimensions) on scale where 1 represented best possible health state. EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS scale ranging from 0-100, where 0=worst imaginable health state and 100=best imaginable health state, where higher states indicated better outcomes. Baseline corresponded to last evaluable assessment before treatment administration.
Time Frame	Baseline, Day 1 of each Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 6, Cycle 7, Cycle 8 and at End of Treatment (any time up to: 141 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Health status population which included participants who received at least one dose of the study drug and with an evaluable EQ-5D-5L at baseline and with at least one post-baseline evaluable EQ-5D-5L. Here 'Number analyzed' signifies participants with available data for each specified category.

Arm/Group Title		Cabazitaxel	Abiraterone Acetate or Enzalutamide
Arm/Group Description:		Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
Overall Number of Participants Analyzed		115	115
Mean (Standard Deviation); Unit of Measure: score on a scale
Cycle 2: VAS	Number Analyzed	108 participants	109 participants
		3.6 (14.4)	0.9 (14.6)
Cycle 3: VAS	Number Analyzed	104 participants	94 participants
		4.5 (15.0)	1.5 (13.4)
Cycle 4: VAS	Number Analyzed	100 participants	77 participants
		4.6 (16.5)	-1.1 (18.2)
Cycle 5: VAS	Number Analyzed	84 participants	57 participants
		0.6 (17.1)	3.2 (17.0)
Cycle 6: VAS	Number Analyzed	68 participants	39 participants
		-1.3 (22.8)	-1.5 (23.1)
Cycle 7: VAS	Number Analyzed	60 participants	32 participants
		2.9 (18.1)	-0.2 (20.1)
Cycle 8: VAS	Number Analyzed	49 participants	23 participants
		2.8 (18.0)	1.2 (19.6)
End of treatment: VAS	Number Analyzed	56 participants	33 participants
		-3.3 (19.3)	-5.9 (23.1)
Cycle 2: Utility Index Score	Number Analyzed	108 participants	109 participants
		0.026 (0.179)	-0.010 (0.178)
Cycle 3: Utility Index Score	Number Analyzed	103 participants	94 participants
		0.041 (0.183)	-0.011 (0.182)
Cycle 4: Utility Index Score	Number Analyzed	99 participants	79 participants
		0.051 (0.176)	-0.002 (0.188)
Cycle 5: Utility Index Score	Number Analyzed	79 participants	59 participants
		0.027 (0.209)	-0.035 (0.185)
Cycle 6: Utility Index Score	Number Analyzed	67 participants	42 participants
		0.015 (0.191)	-0.000 (0.176)
Cycle 7: Utility Index Score	Number Analyzed	60 participants	34 participants
		0.029 (0.182)	0.024 (0.153)
Cycle 8: Utility Index Score	Number Analyzed	47 participants	24 participants
		0.008 (0.213)	-0.014 (0.138)
End of treatment: Utility Index Score	Number Analyzed	56 participants	35 participants
		-0.048 (0.188)	-0.079 (0.200)

14. Secondary Outcome

Title	Radiographic Progression-Free Survival (rPFS) in Participants With Presence and Absence of Biomarker
Description	Circulating tumor cell (CTC) counts were considered as biomarker in a liquid biopsy. rPFS in participants with presence and absence of subtypes of CTC biomarker i.e. chromosomal instability (CIN) and neuroendocrine (NE) was reported in this outcome measure. rPFS was defined as: time (in months) from randomization to the first occurrence of any one of following: radiological tumor progressions (RECIST1.1), progression of bone lesions (PCWG2 criteria) or death due to any cause. Progression (RECIST1.1): at least a 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Progression of bone lesions (PCWG2 criteria): first bone scan with >= 2 new lesions compared to Baseline observed <12 weeks from randomization and confirmed by a second bone scan performed >=6 weeks later; first bone scan with >=2 new lesions compared to Baseline observed >=12 weeks from randomization and new lesions were verified on next bone scan >= 6 weeks later.
Time Frame	From randomization until tumor progression or bone lesion progression, death due to any cause, or data cut-off date whichever comes first (maximum duration: up to 141 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on subset of participants analyzed according to the treatment group allocated by randomization with evaluable samples.

Arm/Group Title		Cabazitaxel	Abiraterone Acetate or Enzalutamide
Arm/Group Description:		Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).	Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks)
Overall Number of Participants Analyzed		109	106
Median (Full Range); Unit of Measure: months
Presence of CIN	Number Analyzed	27 participants	27 participants
		4.2; (2.1 to 11.2)	4.2; (0.03 to 21.0)
Absence of CIN	Number Analyzed	82 participants	79 participants
		8.5; (0.03 to 33.1)	3.4; (0.03 to 28.0)
Presence of NE	Number Analyzed	7 participants	14 participants
		3.0; (2.6 to 11.2)	3.9; (0.03 to 21.0)
Absence of NE	Number Analyzed	102 participants	92 participants
		8.2; (0.03 to 33.1)	3.5; (0.03 to 28.0)

Adverse Events

Time Frame	Adverse event (AE) data was collected from Baseline up to 30 days after the last treatment administration (up to 197 weeks), deaths were collected from baseline up to end of study (up to 197 weeks).
Adverse Event Reporting Description	Reported AEs were TEAEs i.e., AEs that developed/worsened during the 'on-treatment period' (time from first dose of study drug until 30 days after last administration of study drug) assessed for safety population (i.e., all participants who received at least one dose of study drugs and analyzed according to treatment they actually received). All-Cause Mortality data collected during the study was assessed for all randomized participants. Disease progression related death were not reported as AE.
Arm/Group Title	Cabazitaxel		Enzalutamide or Abiraterone
Arm/Group Description	Participants received Cabazitaxel 25 mg/m^2 IV infusion for over 1 hour on Day 1 of each 3 week treatment cycle in combination with Prednisone 10 mg orally once daily and primary prophylactic G-CSF as per investigator decision, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 22 weeks).		Participants received either abiraterone acetate 1000 mg orally once daily from Day 1 to Day 21 of each 3 week treatment cycle in combination with prednisone 5 mg orally twice daily; or enzalutamide 160 mg orally once daily continuously from Day 1 to Day 21 of each 3 week treatment cycle, until radiographic disease progression, unacceptable toxicity, or participant's refusal of further study treatment (median duration = 12.5 weeks).
All-Cause Mortality
	Cabazitaxel		Enzalutamide or Abiraterone
	Affected / at Risk (%)		Affected / at Risk (%)
Total	96/129 (74.42%)		103/126 (81.75%)
Serious Adverse Events
	Cabazitaxel		Enzalutamide or Abiraterone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/126 (38.89%)		50/124 (40.32%)
Blood and lymphatic system disorders
Anaemia † 1	2/126 (1.59%)	2	1/124 (0.81%)	1
Febrile Neutropenia † 1	4/126 (3.17%)	4	0/124 (0.00%)	0
Hyperfibrinolysis † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Neutropenia † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Pancytopenia † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Thrombocytopenia † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Cardiac disorders
Acute Coronary Syndrome † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Angina Pectoris † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Atrial Fibrillation † 1	2/126 (1.59%)	2	0/124 (0.00%)	0
Atrial Flutter † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Atrioventricular Block Complete † 1	0/126 (0.00%)	0	2/124 (1.61%)	2
Cardiac Failure † 1	0/126 (0.00%)	0	2/124 (1.61%)	2
Ear and labyrinth disorders
Vertigo † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Gastrointestinal disorders
Abdominal Pain † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Diarrhoea † 1	2/126 (1.59%)	2	0/124 (0.00%)	0
Diarrhoea Haemorrhagic † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Duodenal Ulcer † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Ileus Paralytic † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Nausea † 1	0/126 (0.00%)	0	3/124 (2.42%)	3
Proctalgia † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Rectal Haemorrhage † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Upper Gastrointestinal Haemorrhage † 1	0/126 (0.00%)	0	2/124 (1.61%)	2
Vomiting † 1	1/126 (0.79%)	1	2/124 (1.61%)	2
General disorders
Asthenia † 1	3/126 (2.38%)	4	1/124 (0.81%)	1
Disease Progression † 1	4/126 (3.17%)	4	8/124 (6.45%)	8
General Physical Health Deterioration † 1	1/126 (0.79%)	1	2/124 (1.61%)	2
Inflammation † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Malaise † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Pain † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Pyrexia † 1	0/126 (0.00%)	0	2/124 (1.61%)	2
Hepatobiliary disorders
Hepatitis † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Infections and infestations
Device Related Sepsis † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Enterobacter Sepsis † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Erysipelas † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Gastroenteritis † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Herpes Zoster † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Neutropenic Infection † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Perineal Cellulitis † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Pneumonia † 1	4/126 (3.17%)	5	1/124 (0.81%)	2
Pulmonary Sepsis † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Sepsis † 1	2/126 (1.59%)	2	0/124 (0.00%)	0
Septic Shock † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Tooth Infection † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Urinary Tract Infection † 1	2/126 (1.59%)	2	3/124 (2.42%)	3
Urinary Tract Infection Bacterial † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Urosepsis † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Injury, poisoning and procedural complications
Femoral Neck Fracture † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Head Injury † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Spinal Compression Fracture † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Toxicity To Various Agents † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Investigations
Alanine Aminotransferase Increased † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Aspartate Aminotransferase Increased † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Gamma-Glutamyltransferase Increased † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Platelet Count Decreased † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Metabolism and nutrition disorders
Decreased Appetite † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Dehydration † 1	0/126 (0.00%)	0	2/124 (1.61%)	2
Hypocalcaemia † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Back Pain † 1	0/126 (0.00%)	0	4/124 (3.23%)	4
Flank Pain † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Pain In Extremity † 1	0/126 (0.00%)	0	2/124 (1.61%)	2
Pathological Fracture † 1	1/126 (0.79%)	2	1/124 (0.81%)	1
Spinal Pain † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain † 1	2/126 (1.59%)	3	2/124 (1.61%)	2
Neuroendocrine Carcinoma Of The Skin † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Oncologic Complication † 1	1/126 (0.79%)	1	1/124 (0.81%)	1
Tumour Pain † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Nervous system disorders
Carotid Artery Stenosis † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Cerebral Haemorrhage † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Cognitive Disorder † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Loss Of Consciousness † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Paraparesis † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Spinal Cord Compression † 1	4/126 (3.17%)	4	3/124 (2.42%)	3
Syncope † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Transient Ischaemic Attack † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Product Issues
Device Dislocation † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Renal and urinary disorders
Acute Kidney Injury † 1	3/126 (2.38%)	4	4/124 (3.23%)	4
Haematuria † 1	1/126 (0.79%)	1	3/124 (2.42%)	3
Hydronephrosis † 1	1/126 (0.79%)	1	1/124 (0.81%)	2
Pyelocaliectasis † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Renal Failure † 1	0/126 (0.00%)	0	3/124 (2.42%)	3
Urinary Retention † 1	1/126 (0.79%)	1	1/124 (0.81%)	1
Urinary Tract Obstruction † 1	0/126 (0.00%)	0	2/124 (1.61%)	2
Reproductive system and breast disorders
Pelvic Pain † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Chronic Obstructive Pulmonary Disease † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Haemoptysis † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Laryngeal Inflammation † 1	1/126 (0.79%)	1	0/124 (0.00%)	0
Pleural Effusion † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Pulmonary Embolism † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Vascular disorders
Hypertension † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Hypertensive Crisis † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
Lymphoedema † 1	0/126 (0.00%)	0	1/124 (0.81%)	1
1 Term from vocabulary, MedDra 23.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Cabazitaxel		Enzalutamide or Abiraterone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	114/126 (90.48%)		104/124 (83.87%)
Blood and lymphatic system disorders
Anaemia † 1	38/126 (30.16%)	75	14/124 (11.29%)	24
Leukopenia † 1	8/126 (6.35%)	12	1/124 (0.81%)	3
Neutropenia † 1	28/126 (22.22%)	35	1/124 (0.81%)	3
Gastrointestinal disorders
Abdominal Pain † 1	10/126 (7.94%)	12	3/124 (2.42%)	3
Constipation † 1	19/126 (15.08%)	27	13/124 (10.48%)	18
Diarrhoea † 1	50/126 (39.68%)	88	8/124 (6.45%)	8
Nausea † 1	29/126 (23.02%)	49	26/124 (20.97%)	31
Stomatitis † 1	10/126 (7.94%)	13	2/124 (1.61%)	3
Vomiting † 1	16/126 (12.70%)	21	14/124 (11.29%)	18
General disorders
Asthenia † 1	33/126 (26.19%)	69	26/124 (20.97%)	37
Fatigue † 1	36/126 (28.57%)	65	21/124 (16.94%)	27
Oedema Peripheral † 1	10/126 (7.94%)	13	11/124 (8.87%)	12
Pain † 1	8/126 (6.35%)	8	6/124 (4.84%)	7
Pyrexia † 1	7/126 (5.56%)	10	7/124 (5.65%)	7
Infections and infestations
Urinary Tract Infection † 1	10/126 (7.94%)	10	4/124 (3.23%)	4
Investigations
Weight Decreased † 1	5/126 (3.97%)	6	7/124 (5.65%)	7
Metabolism and nutrition disorders
Decreased Appetite † 1	16/126 (12.70%)	21	19/124 (15.32%)	21
Hypokalaemia † 1	5/126 (3.97%)	8	7/124 (5.65%)	14
Musculoskeletal and connective tissue disorders
Arthralgia † 1	10/126 (7.94%)	14	20/124 (16.13%)	35
Back Pain † 1	20/126 (15.87%)	22	27/124 (21.77%)	41
Bone Pain † 1	4/126 (3.17%)	4	7/124 (5.65%)	7
Pain In Extremity † 1	6/126 (4.76%)	7	13/124 (10.48%)	18
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain † 1	9/126 (7.14%)	15	9/124 (7.26%)	10
Nervous system disorders
Dysgeusia † 1	15/126 (11.90%)	18	5/124 (4.03%)	7
Neuropathy Peripheral † 1	8/126 (6.35%)	11	3/124 (2.42%)	3
Polyneuropathy † 1	8/126 (6.35%)	12	0/124 (0.00%)	0
Renal and urinary disorders
Haematuria † 1	18/126 (14.29%)	27	5/124 (4.03%)	6
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	7/126 (5.56%)	8	3/124 (2.42%)	5
Skin and subcutaneous tissue disorders
Alopecia † 1	7/126 (5.56%)	7	0/124 (0.00%)	0
Vascular disorders
Hypertension † 1	5/126 (3.97%)	12	8/124 (6.45%)	8
1 Term from vocabulary, MedDra 23.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.

Results Point of Contact

• Name/Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement
• Phone: 800-633-1610 ext 6#
• EMail: Contact-US@sanofi.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

de Wit R, Wulfing C, Castellano D, Kramer G, Eymard JC, Sternberg CN, Fizazi K, Tombal B, Bamias A, Carles J, Iacovelli R, Melichar B, Sverrisdottir A, Theodore C, Feyerabend S, Helissey C, Foster MC, Ozatilgan A, Geffriaud-Ricouard C, de Bono J. Baseline neutrophil-to-lymphocyte ratio as a predictive and prognostic biomarker in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel versus abiraterone or enzalutamide in the CARD study. ESMO Open. 2021 Oct;6(5):100241. doi: 10.1016/j.esmoop.2021.100241. Epub 2021 Aug 24.

Sternberg CN, Castellano D, de Bono J, Fizazi K, Tombal B, Wulfing C, Kramer G, Eymard JC, Bamias A, Carles J, Iacovelli R, Melichar B, Sverrisdottir A, Theodore C, Feyerabend S, Helissey C, Poole EM, Ozatilgan A, Geffriaud-Ricouard C, de Wit R. Efficacy and Safety of Cabazitaxel Versus Abiraterone or Enzalutamide in Older Patients with Metastatic Castration-resistant Prostate Cancer in the CARD Study. Eur Urol. 2021 Oct;80(4):497-506. doi: 10.1016/j.eururo.2021.06.021. Epub 2021 Jul 15.

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• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02485691
• Other Study ID Numbers: LPS14201; 2014-004676-29 ( EudraCT Number ); U1111-1166-5329 ( Other Identifier: UTN )
• First Submitted: June 26, 2015
• First Posted: June 30, 2015
• Results First Submitted: November 12, 2021
• Results First Posted: February 14, 2022
• Last Update Posted: May 27, 2022