A Study of Pertuzumab in Participants With Metastatic Breast Cancer

Objective tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR was defined as the disappearance of all target lesions, and confirmed PR was defined as at least at 30 percent (%) decrease in the sum of the longest diameters of target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. The percentage of participants achieving a best overall response of CR or PR was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100.

Objective tumor response was assessed using RECIST. Confirmed CR was defined as the disappearance of all target lesions, and confirmed PR was defined as at least at 30% decrease in the sum of the longest diameters of target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. Time to response was defined as the time from treatment start to first documented response (ie, CR or PR). Participants with stable disease (SD) were censored from the last tumor assessment, and those with progressive disease (PD) or death were assigned an artificial censoring time of 1000 days. Time to response was estimated using Kaplan-Meier and expressed in weeks.

Objective tumor response was assessed using RECIST. Confirmed CR was defined as the disappearance of all target lesions, and confirmed PR was defined as at least at 30% decrease in the sum of the longest diameters of target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. Duration of response was defined as the time from first documented response (ie, CR or PR) to PD or death. Participants who did not experience PD or death were censored from the last tumor assessment. Duration of response was estimated using Kaplan-Meier and expressed in weeks.

Objective tumor response was assessed using RECIST. Confirmed CR was defined as the disappearance of all target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. The percentage of participants achieving a best overall response of CR was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100.

Objective tumor response was assessed using RECIST. Confirmed CR was defined as the disappearance of all target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. Duration of response was defined as the time from first documented response (ie, CR) to PD or death. Participants who did not experience PD or death were to be censored from the last tumor assessment. Duration of response was to be estimated using Kaplan-Meier.

Objective tumor response was assessed using RECIST. PD was defined as the appearance of new lesion(s) or at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum obtained at Screening or during treatment. Participants who withdrew from the study early for insufficient therapeutic response without tumor assessment for PD were also included within the definition of PD.

Objective tumor response was assessed using RECIST. PD was defined as the appearance of new lesion(s) or at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum obtained at Screening or during treatment. Participants who withdrew from the study early for insufficient therapeutic response without tumor assessment for PD were also included within the definition of PD. Time to progression was defined as the time from treatment start to PD or death. Participants who did not experience PD or death were censored from the last tumor assessment. Time to progression was estimated using Kaplan-Meier and expressed in weeks.

Objective tumor response was assessed using RECIST. PD was defined as the appearance of new lesion(s) or at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum obtained at Screening or during treatment.

Objective tumor response was assessed using RECIST. PD was defined as the appearance of new lesion(s) or at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum obtained at Screening or during treatment. Time to treatment failure was defined as the time from treatment start to PD or early withdrawal from the study for death, toxicity, refusal/noncompliance, insufficient therapeutic response, or failure to return. Participants who did not experience PD or who did not withdraw from the study early were censored from the last tumor assessment. Time to treatment failure was estimated using Kaplan-Meier and expressed in weeks.

The percentage of participants who died was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.

Overall survival was defined as the time from treatment start to death. Participants who did not die during follow-up were to be censored from the last known alive date. Overall survival was to be estimated using Kaplan-Meier.

Objective tumor response was assessed using RECIST. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for PD. The percentage of participants achieving a best overall response of SD was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100.

Serum samples were obtained for pharmacokinetic (PK) assessment using a receptor-binding, enzyme-linked immunosorbent assay (ELISA). Pertuzumab concentrations at each collection point were used to determine the apparent t1/2 by non-compartmental analysis, defined as the time elapsed for pertuzumab concentrations to decrease by 50%. The derived value was averaged among all participants and expressed in days.

Serum samples were obtained for PK assessment using a receptor-binding ELISA. The maximum observed pertuzumab concentration across all collection points was documented. Cmax was averaged among all participants and expressed in micrograms per milliliter (mcg/mL).

Serum samples were obtained for PK assessment using a receptor-binding ELISA. The time of maximum observed pertuzumab concentration across all collection points was documented. Tmax was averaged among all participants and expressed in days.

Serum samples were obtained for PK assessment using a receptor-binding ELISA. Pertuzumab concentrations at each collection point were used to determine AUC to the last measurable observation (AUClast) and AUC extrapolated to infinity (AUCinf) by non-compartmental analysis. The derived values were averaged among all participants and expressed in days by micrograms per milliliter (days*mcg/mL).

Serum samples were obtained for PK assessment using a receptor-binding ELISA. Pertuzumab concentrations at each collection point were used to determine CL by non-compartmental analysis, defined as the rate at which pertuzumab was removed from the body. The derived value was averaged among all participants and expressed in milliliters per day (mL/day).

Serum samples were obtained for PK assessment using a receptor-binding ELISA. Pertuzumab concentrations at each collection point were used to determine the Vss by non-compartmental analysis, defined as the theoretical volume at which the total amount of pertuzumab would be uniformly distributed to produce the desired concentration. The derived value was averaged among all participants and expressed in milliliters (mL).

Serum samples were obtained for PK assessment using a receptor-binding ELISA. Pertuzumab concentrations at each collection point were used to determine the MRT by non-compartmental analysis. The derived value was averaged among all participants and expressed in days.

Echocardiography was performed to determine LVEF, defined as the volume of blood pumped from the left ventricle as a percentage of end-diastolic volume. Theoretically, LVEF may range from 0 to 100%. The number of participants experiencing a drop in LVEF greater than or equal to (≥) 10 or 15 percentage points to a final LVEF of less than (<) 50% is reported here.