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

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.

Time frame: 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.

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.

Time frame: 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 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.

Time frame: 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 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.

Time frame: 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.

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.

Time frame: 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.

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.

Time frame: 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.

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.

Time frame: 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.

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.

Time frame: 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.

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.

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

Time frame: 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.

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.

Time frame: 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.

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.

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

Population: Analysis was performed on ITT 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.

Time frame: 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.

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.

Time frame: From baseline until 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.

Time frame: 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.

Time frame: 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.

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.

Time frame: 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 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.

Time frame: 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.