A Study of Pertuzumab and Trastuzumab Subcutaneous (SC) Treatment in Combination With a Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Percentage of participants with AEs and SAEs was reported. AEs included both SAEs and non-SAEs. The 95% confidence interval (CI) was computed using Clopper-Pearson method.

Time frame: Baseline up to 28 days after last study drug administration (up to 36 months)

Population: Analysis was performed on the Safety population, which included all enrolled participants who received at least one dose of pertuzumab IV or trastuzumab SC.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Intensity of AEs were graded according to NCI CTCAE version 4.0 on a 5-point scale: Grade 1=Mild, intervention not indicated; Grade 2=Moderate, local or noninvasive intervention indicated; Grade 3=Severe or medically significant but not immediately life-threatening; Grade 4= Life-threatening consequences, urgent intervention indicated; and Grade 5=Death related to AE. Percentage of participants with AEs by maximum severity grades was reported.

Time frame: Baseline up to 28 days after last study drug administration (up to 36 months)

Population: Analysis was performed on the Safety population.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Percentage of participants with AEs leading to premature discontinuation of IMPs (pertuzumab and trastuzumab) was reported. AEs included both SAEs and non-SAEs. The 95% CI was computed using Clopper-Pearson method.

Time frame: Baseline up to 28 days after last study drug administration (up to 36 months)

Population: Analysis was performed on the Safety population.

NYHA functional classification includes: Class I (no limitation in physical activity; ordinary physical activity does not cause fatigue, breathlessness or palpitation), Class II (slight limitation of physical activity; ordinary physical activity results in fatigue, palpitation, breathlessness or angina pectoris), Class III (marked limitation of physical activity; less than ordinary activity will lead to symptomatically 'moderate' heart failure) and Class IV (inability to carry out any physical activity without discomfort; symptoms of congestive cardiac failure are present even at rest). Percentage of participants with AEs suspected to be of cardiac origin by maximum NYHA classification was reported.

Time frame: Baseline up to 28 days after last study drug administration (up to 36 months)

Population: Analysis was performed on the Safety population.

LVEF was assessed using echocardiography (ECHO) or multiple-gated acquisition (MUGA) scans. Percentage of participants with LVEF below 50% at any time during the study was reported.

Time frame: Baseline up to 28 days after last study drug administration (up to 36 months)

Population: Analysis was performed on the Safety population.

EFS was defined as the time from the start of treatment until the first documented initiation of non-protocol-specified treatment for metastatic breast cancer, PD, or death from any cause, whichever occurred first. Participants without treatment change, PD, death, or who were lost to follow-up at the time of analysis were censored at the date of the last tumor assessment when non-progression was documented or at the last date of follow-up, whichever was last. Participants without tumor assessment after baseline were censored at baseline unless death occurred before first scheduled tumor assessment. PD was defined as \>/=20% relative increase and \>/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, and/or unequivocal progression of existing non-TLs, or appearance of 1 or more new lesions. Median EFS was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method.

Time frame: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)

Population: Analysis was performed on the ITT population.

Second-line anti-cancer treatment was initiated after disease progression on first-line therapy. Number of participants who started second-line of treatment by treatment type was reported. Participants who received combination treatment were counted for each treatment type.

Time frame: Baseline up to approximately 35 months

Population: Analysis was performed on the ITT population participants who started second-line of treatment.

The OS during second-line therapy was defined as the time from the start of second-line therapy (failure of first-line therapy) until death from any cause. Participants alive at the time of analysis and participants who were lost to follow-up were censored at their last clinical assessment date. Median OS during second-line therapy was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method.

Time frame: From start of second-line of treatment (any time from baseline up to 35 months) up to death due to any cause or study end (up to approximately 36 months)

Population: Analysis was performed on the ITT population participants who started second-line of treatment.

The OS was defined as the time from the start of treatment until death from any cause. Participants alive at the time of analysis and participants who were lost to follow-up were censored at their last clinical assessment date. Median OS was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method.

Time frame: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)

Population: Analysis was performed on the ITT population.

Percentage of participants who died due to any cause during the study was reported.

Time frame: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)

Population: Analysis was performed on the ITT population.

Percentage of participants who died from any cause during second-line of treatment was reported.

Time frame: From start of second-line of treatment (any time from baseline up to 35 months) up to death due to any cause or study end (up to approximately 36 months)

Population: Analysis was performed on the ITT population participants who started second-line of treatment.

BOR was defined as a confirmed CR or PR. All measurable lesions up to a maximum of 2 lesions per organ and 5 in total were identified as target lesions (TLs) and recorded at baseline. A sum of the diameters (longest for non-nodal lesions, short axis \[SA\] for nodal lesions) for all TLs was calculated as baseline sum of diameters (SD). All other lesions (or sites of disease) were identified as non-TLs and were recorded at baseline. CR was defined as the disappearance of all TLs and SA reduction to less than (\<) 10 millimeter (mm) for nodal TLs/ non-TLs. PR was defined as greater than or equal to (\>/=) 30% decrease in SD of TLs, taking as reference the baseline SD. Confirmation of response at a consecutive tumor assessment at least 4 weeks apart was required. The 95% CI was computed using Clopper-Pearson method.

Time frame: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)

Population: Analysis was performed on ITT population. Only participants with measurable disease at baseline were included in the analysis. Participants without a post-baseline tumor assessment were considered non-responders.

For TLs, PD was defined as \>/=20% relative increase and \>/=5 mm of absolute increase in the SD, taking as reference the smallest SD recorded since treatment started or the appearance of 1 or more new lesions. For non-TLs, PD was defined as appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs.

Time frame: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)

Population: Analysis was performed on the ITT population.

PFS was defined as the time from start of treatment until first documented PD or death from any cause, whichever occurred first. Participants without PD, death, or who were lost to follow-up at the time of analysis were censored at the date of the last tumor assessment when non-progression was documented or at the last date of follow-up, whichever was last. Participants without tumor assessment data after the baseline were censored at baseline unless death occurred before first scheduled tumor assessment. PD was defined as \>/=20% relative increase and \>/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, and/or unequivocal progression of existing non-TLs, or appearance of 1 or more new lesions. Median PFS was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method.

Time frame: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)

Population: Analysis was performed on the ITT population.