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

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)

Population: Analysis was performed on ITT population.

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)

Population: 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.

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)

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

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)

Population: 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.

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)

Population: Analysis was performed on ITT population.

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)

Population: Analysis was performed on ITT population.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: Analysis was performed on ITT population.

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)

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

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)

Population: 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.

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)

Population: 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.

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)

Population: Analysis was performed on ITT population.