Study of Pembrolizumab (MK-3475) Plus Docetaxel Versus Placebo Plus Docetaxel in Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-921/KEYNOTE-921)

OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit Kaplan-Meier (K-M) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.

Time frame: Up to 36.5 months

Population: All randomized participants in the intent to treat population who had data available for analysis

rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Radiological progression as per RECIST 1.1 was ≥20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for ≥6 weeks. The rPFS was calculated using the product-limit K-M method for censored data. Participants without a rPFS event were censored at the date of last disease assessment.

Time frame: Up to approximately 28 months

Population: All randomized participants in the intent to treat population who had data available for analysis

DOR was the time from first documented evidence of complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease \[NED\] on bone scan per PCWG) or partial response (PR: ≥30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable \[NE\], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG) until progressive disease (PD) or death. PD per RECIST 1.1 was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. PD per PCWG was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare and were persistent for ≥6 weeks. The DOR was calculated using the product-limit K-M method for censored data. If a participant had not progressed, the participant was censored at the date of last disease assessment.

Time frame: Up to 36.5 months

Population: All randomized participants in the intent to treat population, who demonstrated a CR or PR, and had data available for analysis

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE is presented.

Time frame: Up to approximately 27 months

Population: All participants who received ≥1 dose of study treatment

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE is presented.

Time frame: Up to approximately 30 months

Population: All participants who received ≥1 dose of study treatment

ORR was defined as the percentage of participants with complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease (NED) on bone scan per PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable \[NE\], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG).

Time frame: Up to 36.5 months

Population: All randomized participants in the intent to treat population, with measurable disease at baseline, and had data available for analysis

The Prostate-specific Antigen (PSA) response rate was the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by ≥50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed ≥3 weeks from the original response. The analysis was performed on participants who had baseline PSA measurements.

Time frame: Up to 36.5 months

Population: All randomized participants in the intent to treat population, who had a PSA measurement at baseline, and had data available for analysis

SSRE was the time from randomization to the first symptomatic skeletal-related event defined as: 1. Use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms 2. Occurrence of new symptomatic pathologic bone fracture (vertebral or non-vertebral) 3. Occurrence of spinal cord compression 4. Tumor-related orthopedic surgical intervention, whichever occurs first. The SSRE was calculated using the product-limit K-M method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment.

Time frame: Up to 36.5 months

Population: All randomized participants in the intent to treat population who had data available for analysis

TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product-limit K-M method for censored data. Any participant not known to have further subsequent therapy or death was censored at the last known time that no subsequent new anti-cancer therapy was received.

Time frame: Up to approximately 28 months

Population: All randomized participants in the intent to treat population who had data available for analysis

TTPP was the time from randomization to pain progression (PP) based on BPI-SF Item 3 and AQA score. BPI-SF assesses pain intensity; for item 3, participant responses to Please rate your pain at its worst in the last 24 hours are scored from 0 (no pain) to 10 (worst pain). A higher score indicates greater pain. AQA captures the intensity of analgesic use in pain management, scored from 0 (no analgesic) to 7 (strong opioid use). A higher score indicates higher intensity of analgesic use. For participants asymptomatic at baseline, PP was ≥2-point change from baseline in BPI-SF item 3 score OR initiation of opioid use. For participants symptomatic at baseline, PP was ≥2-point change from baseline in the BPI-SF Item 3 score, a score of ≥4 and no decrease in average opioid use OR any increase in opioid use (e.g., 1 point change in AQA score). TTPP was assessed by product-limit K-M method. Participants with \>2 consecutive unevaluable visits were censored at the last evaluable assessment.

Time frame: Up to 36.5 months

Population: All participants in the patient-reported outcomes (PRO) full analysis set who received ≥1 dose of study treatment and who had ≥1 PRO assessment available

The time to PSA progression was the time from randomization to PSA progression. The PSA progression date was defined as the date of: 1. ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there was PSA decline from baseline; OR 2. ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there was no PSA decline from baseline Time to PSA progression was calculated using the product-limit K-M method for censored data. Participants without PSA progression were censored at the last evaluable assessment.

Time frame: Up to 36.5 months

Population: All randomized participants in the intent to treat population, who had a PSA measurement at baseline, and had data available for analysis

The time to radiographic soft tissue progression was defined as the time from randomization to radiographic soft tissue progression per soft tissue rules of PCWG-modified RECIST 1.1 as assessed by BICR. Progression was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered progression. Time to radiographic soft tissue progression was calculated using the product-limit K-M method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment.

Time frame: Up to 36.5 months

Population: All randomized participants in the intent to treat population who had data available for analysis