A Study of Pertuzumab in Participants With Prostate Cancer

Time to disease progression was defined by time in weeks from start of therapy to the onset of the earliest of the following events. 1) PSA progression as defined by the PSAWG, 2) Evidence of disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 3) One bone scan at least 6 months subsequent to baseline demonstrating 2 or more new skeletal lesions and 4) An event due to metastatic prostate cancer requiring intervention.

Overall objective response by RECIST criteria (CR or PR) was to be defined for participants who had measurable disease at baseline or developed new lesions post-baseline. The longest diameter only for all target lesions was measured and the following responses recorded: CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the longest diameter as compared to the baseline sum longest diameter.

Time to response was the date of the first documentation of PSA response.

Duration of PSA Response was measured from first 50% decline in PSA compared to baseline until the time at which there was an increase of ≥50% from the PSA nadir, provided the absolute increase was at least 5 nanograms per milliliter (ng/ml). The increase must have been confirmed by a second consecutive measurement that was at least 50% above the nadir.

For participants with measurable disease, duration of response was defined as first documentation of tumor response, either a PR or CR, to first documentation of PD or death. Participants who never progressed or died were censored at their last tumor measurement.

Disease progression was defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Non-progression included participants who had responded plus those who had not responded and not progressed within the first 3 cycles.

Time to disease progression was defined by time in weeks from start of therapy to the onset of the earliest of the following events: 1) Opioid therapy, 2) Radiation therapy, 3) Glucocorticoid therapy, 4) Radionuclide therapy or 5) Chemotherapy.

Overall survival was defined as the interval of time in weeks between start of treatment and day of death. Participants who did not die while being followed were censored at the last time that they were known to be alive.

Time to Treatment Failure was time to the first documentation of progressive disease, day of death while on study (or 30 days after withdrawing from the trial) or day of early discontinuation due to toxicity (adverse events or abnormal laboratory value), refusal of treatment/refusing to cooperate/withdrawing consent, insufficient therapeutic response, or failure to return, whichever is earliest, after the start of treatment. Participants who did not experience any of the above events while on study were censored on the day of their last PSA or tumor measurement, whichever was later.

Bone alkaline phosphatase (BAP) is the bone-specific isoform of alkaline phosphatase. Serum Bone alkaline phosphatase is used to measure osteoporosis and is measured as units per liter (u/L).

In bone physiology, the N-terminal telopeptide (or more formally, amino-terminal collagen crosslinks, and known by the acronym NTX) is a telopeptide that can be used as a biomarker to measure the rate of bone turnover. NTX can be measured in the urine (uNTX) or serum (serum NTX).

The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as micrograms times days per milliliter (µg*day/mL)

The AUC0-last is calculated from time 0 (prior to administration of medication) to last measured data point. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption.

Cmax is the maximum (or peak) plasma concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and prior to the administration of a second dose. Cmax is measured as micrograms per mL (μg/mL).

Cmax refers to the maximum (or peak) plasma concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered and prior to the administration of a second dose. tmax is the time at which the Cmax is observed.

t1/2 is the time in days required for the concentration of the drug to reach half of its original value

Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per day (mL/day).

The volume of distribution at steady state (Vss), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma.

MRT is the average time that pertuzumab is present in the systemic circulation and is measured in days.