Early Breast Cancer
Conditions
Brief summary
This is a global Phase III, two-arm, open-label, multicenter, randomized study to investigate the pharmacokinetics, efficacy, and safety of the fixed-dose combination (FDC) of pertuzumab and trastuzumab for subcutaneous (SC) administration in combination with chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer in the neoadjuvant/adjuvant setting.
Interventions
DRUGCyclophosphamide
Cyclophosphamide 600 mg/m2 will be administered IV on Day 1 of each cycle of treatment (as part of ddAC Q2W or AC Q3W) for Cycles 1-4.
DRUGDoxorubicin
Doxorubicin 60 mg/m2 will be administered IV on Day 1 of each cycle of treatment (as part of either ddAC Q2W or AC Q3W) for Cycles 1-4.
DRUGDocetaxel
As part of one of the two investigator's choices of chemotherapy (AC followed by docetaxel), docetaxel 75 mg/m2 will be administered IV on Day 1 of Cycle 5 and then 100 mg/m2 IV at the discretion of the investigator for Cycles 6-8 (Q3W), if no dose-limiting toxicity occurs.
DRUGPaclitaxel
As part of one of the two investigator's choices of chemotherapy (ddAC followed by paclitaxel), paclitaxel 80 mg/m2 will be administered IV QW for 12 weeks.
DRUGPertuzumab IV
Pertuzumab will be administered as a fixed non-weight-based dose of 840-mg IV loading dose and then 420-mg IV maintenance dose Q3W.
DRUGFDC of Pertuzumab and Trastuzumab SC
The FDC of pertuzumab and trastuzumab will be administered SC at a fixed non-weight-based dose. A loading dose of 1200 mg SC pertuzumab and 600 mg SC trastuzumab is then followed by a maintenance dose of 600 mg SC pertuzumab and 600 mg SC trastuzumab Q3W.
DRUGTrastuzumab IV
Trastuzumab will be administered as an 8-mg/kg IV loading dose and then 6 mg/kg IV maintenance dose Q3W.
DRUGTrastuzumab SC
After surgery (from Cycle 9 onwards), participants in Arm A will be allowed to switch from trastuzumab IV to trastuzumab SC, at the discretion of the investigator, in the countries where trastuzumab SC is routinely used. For participants who switch, a fixed dose of 600 mg trastuzumab SC (irrespective of the patient's weight) will be administered in the adjuvant phase.
PROCEDURESurgery
Participants in both cohorts are scheduled to undergo surgery after 8 cycles of neoadjuvant therapy. Participants may undergo breast-conserving surgery or mastectomy according to routine clinical practice.
RADIATIONPost-operative Radiotherapy
If indicated, radiotherapy is given after chemotherapy and surgery, during adjuvant HER2-targeted therapy and hormone therapy (for hormone-receptor positive disease).
DRUGHormone Therapy
For hormone receptor positive breast cancer, tamoxifen or aromatase inhibitors will be allowed as adjuvant hormone therapy for postmenopausal participants and with ovarian suppression or ablation for premenopausal participants in countries where it has been registered for this indication. Its use must be consistent with the registered label. Hormone therapy is given after chemotherapy and surgery during adjuvant HER2-targeted therapy.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to comply with the study protocol, in the investigator's judgment * Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 * Female and male patients with Stage II - IIIC (T2-T4 plus any N, or any T plus N1-N3, M0), locally advanced, inflammatory, or early-stage, unilateral, and histologically confirmed invasive breast cancer * Primary tumor \>2 cm in diameter, or node-positive disease (clinically or on imaging, and node positivity confirmed with cytology and/or histopathology) * HER2-positive breast cancer confirmed by a central laboratory prior to study enrollment. HER2-positive status will be determined based on pretreatment breast biopsy material. * Hormone receptor status of the primary tumor, centrally confirmed * Patient agreement to undergo mastectomy or breast conserving surgery after neoadjuvant therapy * Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue block for central confirmation of HER2 and hormone receptor status and additional biomarker research * Baseline left ventricular ejection fraction (LVEF) ≥55% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) * For women of childbearing potential (WOCBP) who are sexually active: agreement to remain abstinent or use one highly effective non-hormonal contraceptive method with a failure rate of \<1% per year, or two effective non-hormonal contraceptive methods during the treatment period and for 7 months after the last dose of HER2-targeted therapy, and agreement to refrain from donating eggs during this same period * For men: men must remain abstinent or use a condom with a spermicidal product during the treatment period and for 7 months after the last dose of HER2-targeted therapy to avoid exposing the embryo. Men must refrain from donating sperm during this same period. * A negative serum pregnancy test must be available prior to randomization for WOCBP, unless they have undergone surgical sterilization * No major surgical procedure unrelated to breast cancer within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
Exclusion criteria
* Stage IV (metastatic) breast cancer * Patients with a history of invasive breast cancer * Patients with a history of concurrent or previously treated non-breast malignancies except for appropriately treated 1) non-melanoma skin cancer and/or 2) in situ carcinomas, including cervix, colon, and skin * Patients who have received any previous systemic therapy for treatment or prevention of breast cancer, or radiation therapy for treatment of cancer * Patients who have a past history of ductal carcinoma in situ or lobular carcinoma in situ if they have received any systemic therapy for its treatment or radiation therapy to the ipsilateral breast * Patients with high-risk for breast cancer who have received chemo-preventative drugs in the past are not allowed to enter the study * Patients with multicentric breast cancer, unless all tumors are HER2-positive * Patients with bilateral breast cancer * Patients who have undergone an excisional biopsy of primary tumor and/or axillary lymph nodes * Axillary lymph node dissection prior to initiation of neoadjuvant therapy * Sentinel lymph node biopsy prior to neoadjuvant therapy * Treatment with any investigational drug within 28 days prior to randomization * Serious cardiac illness or medical conditions * Inadequate bone marrow function, renal function or impaired liver function * Current severe, uncontrolled systemic disease that may interfere with planned treatment * Pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the last dose of HER2-targeted therapy * Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study * Known active liver disease, for example, active viral hepatitis infection, autoimmune hepatic disorders, or sclerosing cholangitis * Concurrent, serious, uncontrolled infections, or known infection with HIV * Known hypersensitivity to study drugs, excipients, and/or murine proteins * Current chronic daily treatment with corticosteroids * History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, colon, skin, and/or non-melanoma skin carcinoma * History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease, coronary heart disease, clinically significant electrolyte abnormalities, or family history of sudden unexplained death or long QT syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Serum Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8) | Pre-dose on Cycle 8, Day 1 (up to 21 weeks) | The observed pertuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by \>20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a subcutaneous injection site other than thigh was used, if the Cycle 8 pre-dose and post-dose samples were switched, and an assay error impacting Ctrough measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment | Following completion of surgery (up to 33 weeks) | Total pCR (tpCR) was defined as eradication of invasive disease in the breast and axilla; that is, ypT0/is ypN0, according to the local pathologists' assessment. Pathologic response to therapy was determined at the time of surgery. The tpCR rate is the percentage of participants in the ITT population who achieved a tpCR. Participants with missing data for tpCR (i.e., do not undergo surgery or have an invalid pCR assessment) were included in the analysis and classified as non-responders. Rates of tpCR were calculated in each treatment arm and were assessed using the difference between the Arm B: Pertuzumab and Trastuzumab FDC SC and the Arm A: Pertuzumab IV and Trastuzumab IV tpCR rates and corresponding 95% Clopper-Pearson confidence intervals (CIs). The difference between the tpCR rates along with corresponding 95% Hauck-Anderson CIs were calculated. The lower bound of the CI will reliably reflect the largest tpCR difference that can be considered unlikely. |
| Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria | At 1, 2, 3, and 4 years | iDFS (excluding SPNBC) is defined as the time from the first date of no disease (i.e., the date of primary surgery) to the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer reccurrence; distant recurrence; contralateral invasive breast cancer; or death attributable to any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse. |
| Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria | At 1, 2, 3, and 4 years | Invasive disease-free survival (iDFS) including second primary non-breast cancer (SPNBC) is defined as the time from the first date of no disease (i.e., the date of primary surgery) to the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer reccurrence; distant recurrence; contralateral invasive breast cancer; or death attributable to any cause. It also includes SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site). |
| Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria | At 1, 2, 3, and 4 years | Event-free survival (EFS) excluding second primary non-breast cancer (SPNBC) is defined as the time from enrollment to the first occurrence of one of the following events: breast cancer progression; breast cancer recurrence; or death from any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse. |
| Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria | At 1, 2, 3, and 4 years | Event-free survival (EFS) including second primary non-breast cancer (SPNBC) is defined as the time from enrollment to the first occurrence of one of the following events: breast cancer progression; breast cancer recurrence; or death from any cause. It also includes SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site). |
| Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria | At 1, 2, 3, and 4 years | The distant recurrence-free interval (DRFI) is defined as the time between randomization and the date of distant breast cancer recurrence. |
| Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8) | Pre-dose on Cycle 8, Day 1 (up to 21 weeks) | The observed trastuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by \>20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a subcutaneous injection site other than thigh was used, if the Cycle 8 pre-dose and post-dose samples were switched, and an assay error impacting Ctrough measurement. |
| Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months) | The adverse event (AE) severity grading scale for the NCI CTCAE v4.0 was used for assessing AE severity. Any AEs that were not specifically listed in the NCI CTCAE, v4.0 were graded per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. The terms severe and serious are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade. |
| Number of Participants With a Primary Cardiac Event During the Neoadjuvant Phase | From first dose of study treatment until the completion of neoadjuvant therapy (24 weeks) | A primary cardiac event is defined as the occurrence of either of the following events: - Incidence of a symptomatic ejection fraction decrease (heart failure) of New York Heart Association (NYHA) Class III or IV and a drop in left ventricular ejection fraction (LVEF) of at least 10-percentage points from baseline and to below 50%; or - Cardiac death, defined as: Definite cardiac death (due to heart failure, myocardial infarction, or documented primary arrhythmia); or, Probable cardiac death (sudden unexpected death within 24 hours of a definite or probable cardiac event \[e.g., syncope, cardiac arrest, chest pain, infarction, arrhythmia\] without documented etiology). |
| Number of Participants With a Secondary Cardiac Event During the Neoadjuvant Phase | From first dose of study treatment until the completion of neoadjuvant therapy (24 weeks) | A secondary cardiac event is defined as asymptomatic or mildly symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II, defined as a left ventricular ejection fraction (LVEF) decrease of at least 10-percentage points below the baseline measurement to an absolute LVEF value of \<50% confirmed by a second assessment within approximately 3 weeks. |
| Number of Participants With a Primary Cardiac Event During the Adjuvant Phase | From surgery until 28 days after the last dose of adjuvant treatment (42 weeks) | A primary cardiac event is defined as the occurrence of either of the following events: - Incidence of a symptomatic ejection fraction decrease (heart failure) of New York Heart Association (NYHA) Class III or IV and a drop in left ventricular ejection fraction (LVEF) of at least 10-percentage points from baseline and to below 50%; or - Cardiac death, defined as: Definite cardiac death (due to heart failure, myocardial infarction, or documented primary arrhythmia); or, Probable cardiac death (sudden unexpected death within 24 hours of a definite or probable cardiac event \[e.g., syncope, cardiac arrest, chest pain, infarction, arrhythmia\] without documented etiology). |
| Number of Participants With a Secondary Cardiac Event During the Adjuvant Phase | From surgery until 28 days after the last dose of adjuvant treatment (42 weeks) | A secondary cardiac event is defined as asymptomatic or mildly symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II, defined as a left ventricular ejection fraction (LVEF) decrease of at least 10-percentage points below the baseline measurement to an absolute LVEF value of \<50% confirmed by a second assessment within approximately 3 weeks. |
| Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months) | Clinical laboratory tests were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest (worst) severity grade (according to NCI-CTCAE v4.0) post-baseline. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a medical intervention or a change in concomitant therapy. For a participant with multiple post-baseline abnormalities, only the highest (worst) grade for a given laboratory test is reported. 'Any Grade' indicates the total number of participants with a post-baseline abnormality of any grade for the specified test. |
| Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival | At 1, 2, 3, and 4 years | Overall survival is defined as the time from randomization to death from any cause. |
Countries
Argentina, Belgium, Brazil, Canada, Czechia, France, Germany, Italy, Japan, Mexico, Poland, Russia, South Korea, Spain, Taiwan, Thailand, Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 607 patients were screened, 500 of whom were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks (Q2W) (given with granulocyte colony-stimulating factor \[G-CSF\] support as needed according to local guidelines) followed by paclitaxel QW for 12 weeks; or 2) 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles. | 252 |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy Participants received 8 cycles of investigator's choice of neoadjuvant chemotherapy. This included either: 1) 4 cycles of ddAC Q2W (given with G-CSF support as needed according to local guidelines) followed by paclitaxel once every week (QW) for 12 weeks; or 2) 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab was given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the FDC of pertuzumab and trastuzumab SC for a total of 18 cycles. | 248 |
| Total | 500 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Neoadjuvant Treatment Phase (24 Weeks) | Adverse Event | 3 | 5 |
| Neoadjuvant Treatment Phase (24 Weeks) | Death | 1 | 1 |
| Neoadjuvant Treatment Phase (24 Weeks) | Other | 1 | 2 |
| Neoadjuvant Treatment Phase (24 Weeks) | Progressive Disease | 3 | 3 |
| Neoadjuvant Treatment Phase (24 Weeks) | Protocol Violation | 0 | 1 |
| Neoadjuvant Treatment Phase (24 Weeks) | Withdrawal by Subject | 1 | 2 |
| Surgery & Adjuvant Treatment (42 Weeks) | Adverse Event | 12 | 7 |
| Surgery & Adjuvant Treatment (42 Weeks) | Death | 1 | 1 |
| Surgery & Adjuvant Treatment (42 Weeks) | Disease Relapse | 4 | 1 |
| Surgery & Adjuvant Treatment (42 Weeks) | Lack of Efficacy | 0 | 2 |
| Surgery & Adjuvant Treatment (42 Weeks) | Other | 7 | 2 |
| Surgery & Adjuvant Treatment (42 Weeks) | Physician Decision | 3 | 2 |
| Surgery & Adjuvant Treatment (42 Weeks) | Progressive Disease | 4 | 0 |
| Surgery & Adjuvant Treatment (42 Weeks) | Withdrawal by Subject | 2 | 2 |
| Treatment-Free Follow-Up (up to 3 Years) | Death | 10 | 11 |
| Treatment-Free Follow-Up (up to 3 Years) | Lost to Follow-up | 4 | 1 |
| Treatment-Free Follow-Up (up to 3 Years) | Withdrawal by Subject | 10 | 10 |
Baseline characteristics
| Characteristic | Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Total | Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy |
|---|---|---|---|
| Age, Continuous | 50.3 Years STANDARD_DEVIATION 10.8 | 51.0 Years STANDARD_DEVIATION 10.8 | 51.7 Years STANDARD_DEVIATION 10.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 32 Participants | 74 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 200 Participants | 389 Participants | 189 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 20 Participants | 37 Participants | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 10 Participants | 20 Participants | 10 Participants |
| Race (NIH/OMB) Asian | 54 Participants | 105 Participants | 51 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 19 Participants | 35 Participants | 16 Participants |
| Race (NIH/OMB) White | 164 Participants | 329 Participants | 165 Participants |
| Randomization Stratification Factors: Clinical Stage at Presentation Stage IIIB-IIIC | 51 Participants | 101 Participants | 50 Participants |
| Randomization Stratification Factors: Clinical Stage at Presentation Stage II-IIIA | 201 Participants | 399 Participants | 198 Participants |
| Randomization Stratification Factors: Hormone Receptor Status ER Negative and PgR Negative | 97 Participants | 193 Participants | 96 Participants |
| Randomization Stratification Factors: Hormone Receptor Status ER Positive and PgR Positive | 155 Participants | 306 Participants | 151 Participants |
| Randomization Stratification Factors: Hormone Receptor Status Unknown | 0 Participants | 1 Participants | 1 Participants |
| Randomization Stratification Factors: Neoadjuvant Chemotherapy Regimen AC Followed by Docetaxel | 132 Participants | 260 Participants | 128 Participants |
| Randomization Stratification Factors: Neoadjuvant Chemotherapy Regimen ddAC Followed by Paclitaxel | 120 Participants | 240 Participants | 120 Participants |
| Sex: Female, Male Female | 250 Participants | 498 Participants | 248 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 252 | 14 / 248 |
| other Total, other adverse events | 251 / 252 | 248 / 248 |
| serious Total, serious adverse events | 52 / 252 | 49 / 248 |
Outcome results
Primary
Trough Serum Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8)
The observed pertuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by \>20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a subcutaneous injection site other than thigh was used, if the Cycle 8 pre-dose and post-dose samples were switched, and an assay error impacting Ctrough measurement.
Time frame: Pre-dose on Cycle 8, Day 1 (up to 21 weeks)
Population: Per Protocol PK Population: includes only participants who adhered to the pre-specified criteria for the schedule of pharmacokinetic assessments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Trough Serum Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8) | 72.4 micrograms per millilitre (μg/mL) | Geometric Coefficient of Variation 34.1 |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Trough Serum Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8) | 88.7 micrograms per millilitre (μg/mL) | Geometric Coefficient of Variation 33.6 |
Comparison: The null hypothesis was that the pertuzumab Arm A SC dose is inferior to the pertuzumab Arm B IV dose (i.e., the CtroughSC/CtroughIV geometric mean ratio of the SC dose of pertuzumab relative to the IV dose is not greater than 0.8).90% CI: [1.14, 1.31]
Secondary
Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8)
The observed trastuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by \>20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a subcutaneous injection site other than thigh was used, if the Cycle 8 pre-dose and post-dose samples were switched, and an assay error impacting Ctrough measurement.
Time frame: Pre-dose on Cycle 8, Day 1 (up to 21 weeks)
Population: Per Protocol PK Population: includes only participants who adhered to the pre-specified criteria for the schedule of pharmacokinetic assessments.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8) | 43.2 micrograms per milllilitre (μg/mL) | Geometric Coefficient of Variation 34.7 |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8) | 57.5 micrograms per milllilitre (μg/mL) | Geometric Coefficient of Variation 37 |
Comparison: The null hypothesis was that the trastuzumab Arm B SC dose is inferior to the Arm A trastuzumab IV dose (i.e., the CtroughSC/CtroughIV geometric mean ratio of the SC dose of trastuzumab relative to the IV dose is not greater than 0.8).90% CI: [1.24, 1.43]
Secondary
Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival
Overall survival is defined as the time from randomization to death from any cause.
Time frame: At 1, 2, 3, and 4 years
Population: ITT Population. The number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for an event.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival | 3 Years | 96.73 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival | 1 Year | 99.60 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival | 2 Years | 98.38 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival | 4 Years | 95.47 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival | 1 Year | 99.19 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival | 3 Years | 95.83 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival | 4 Years | 94.13 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival | 2 Years | 96.68 Percentage of participants |
p-value: 0.560995% CI: [0.58, 2.72]Log Rank
Secondary
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria
The distant recurrence-free interval (DRFI) is defined as the time between randomization and the date of distant breast cancer recurrence.
Time frame: At 1, 2, 3, and 4 years
Population: ITT Population. The number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for an event.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria | 1 Year | 99.59 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria | 2 Years | 95.88 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria | 3 Years | 93.77 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria | 4 Years | 92.49 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria | 4 Years | 91.92 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria | 1 Year | 99.58 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria | 3 Years | 93.23 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria | 2 Years | 95.37 Percentage of participants |
p-value: 0.629195% CI: [0.61, 2.24]Log Rank
Secondary
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria
Event-free survival (EFS) including second primary non-breast cancer (SPNBC) is defined as the time from enrollment to the first occurrence of one of the following events: breast cancer progression; breast cancer recurrence; or death from any cause. It also includes SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).
Time frame: At 1, 2, 3, and 4 years
Population: ITT Population. The number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for an event.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria | 1 Year | 96.38 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria | 2 Years | 91.47 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria | 3 Years | 88.53 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria | 4 Years | 87.22 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria | 4 Years | 85.75 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria | 1 Year | 97.54 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria | 3 Years | 87.04 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria | 2 Years | 90.41 Percentage of participants |
p-value: 0.547495% CI: [0.71, 1.88]Log Rank
Secondary
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria
Event-free survival (EFS) excluding second primary non-breast cancer (SPNBC) is defined as the time from enrollment to the first occurrence of one of the following events: breast cancer progression; breast cancer recurrence; or death from any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse.
Time frame: At 1, 2, 3, and 4 years
Population: ITT Population. The number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for an event.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria | 3 Years | 89.77 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria | 1 Year | 96.79 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria | 4 Years | 88.47 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria | 2 Years | 92.29 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria | 4 Years | 86.57 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria | 2 Years | 91.67 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria | 3 Years | 88.29 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria | 1 Year | 97.95 Percentage of participants |
p-value: 0.484495% CI: [0.72, 1.98]Log Rank
Secondary
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria
Invasive disease-free survival (iDFS) including second primary non-breast cancer (SPNBC) is defined as the time from the first date of no disease (i.e., the date of primary surgery) to the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer reccurrence; distant recurrence; contralateral invasive breast cancer; or death attributable to any cause. It also includes SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).
Time frame: At 1, 2, 3, and 4 years
Population: The analysis population included all participants who had undergone surgery. The number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for an event.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria | 1 Year | 95.63 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria | 2 Years | 92.10 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria | 3 Years | 89.39 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria | 4 Years | 88.27 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria | 2 Years | 89.44 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria | 4 Years | 87.64 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria | 1 Year | 96.94 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria | 3 Years | 88.54 Percentage of participants |
p-value: 0.599295% CI: [0.68, 1.97]Log Rank
Secondary
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria
iDFS (excluding SPNBC) is defined as the time from the first date of no disease (i.e., the date of primary surgery) to the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer reccurrence; distant recurrence; contralateral invasive breast cancer; or death attributable to any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse.
Time frame: At 1, 2, 3, and 4 years
Population: The analysis population included all participants who had undergone surgery. The number analyzed at each landmark timepoint represents the number of participants who were remaining at risk for an event.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria | 1 Year | 96.07 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria | 2 Years | 92.98 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria | 3 Years | 90.71 Percentage of participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria | 4 Years | 89.60 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria | 4 Years | 88.50 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria | 1 Year | 97.37 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria | 3 Years | 89.86 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria | 2 Years | 90.75 Percentage of participants |
p-value: 0.521695% CI: [0.68, 2.11]Log Rank
Secondary
Number of Participants With a Primary Cardiac Event During the Adjuvant Phase
A primary cardiac event is defined as the occurrence of either of the following events: - Incidence of a symptomatic ejection fraction decrease (heart failure) of New York Heart Association (NYHA) Class III or IV and a drop in left ventricular ejection fraction (LVEF) of at least 10-percentage points from baseline and to below 50%; or - Cardiac death, defined as: Definite cardiac death (due to heart failure, myocardial infarction, or documented primary arrhythmia); or, Probable cardiac death (sudden unexpected death within 24 hours of a definite or probable cardiac event \[e.g., syncope, cardiac arrest, chest pain, infarction, arrhythmia\] without documented etiology).
Time frame: From surgery until 28 days after the last dose of adjuvant treatment (42 weeks)
Population: Safety Population: includes all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With a Primary Cardiac Event During the Adjuvant Phase | Any Primary Cardiac Event | 1 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With a Primary Cardiac Event During the Adjuvant Phase | Heart Failure and Significant LVEF Decline | 1 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With a Primary Cardiac Event During the Adjuvant Phase | Cardiac Death (Definite or Probable) | 1 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With a Primary Cardiac Event During the Adjuvant Phase | Any Primary Cardiac Event | 2 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With a Primary Cardiac Event During the Adjuvant Phase | Heart Failure and Significant LVEF Decline | 2 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With a Primary Cardiac Event During the Adjuvant Phase | Cardiac Death (Definite or Probable) | 0 Participants |
Secondary
Number of Participants With a Primary Cardiac Event During the Neoadjuvant Phase
A primary cardiac event is defined as the occurrence of either of the following events: - Incidence of a symptomatic ejection fraction decrease (heart failure) of New York Heart Association (NYHA) Class III or IV and a drop in left ventricular ejection fraction (LVEF) of at least 10-percentage points from baseline and to below 50%; or - Cardiac death, defined as: Definite cardiac death (due to heart failure, myocardial infarction, or documented primary arrhythmia); or, Probable cardiac death (sudden unexpected death within 24 hours of a definite or probable cardiac event \[e.g., syncope, cardiac arrest, chest pain, infarction, arrhythmia\] without documented etiology).
Time frame: From first dose of study treatment until the completion of neoadjuvant therapy (24 weeks)
Population: Safety Population: includes all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With a Primary Cardiac Event During the Neoadjuvant Phase | Any Primary Cardiac Event | 0 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With a Primary Cardiac Event During the Neoadjuvant Phase | Heart Failure and Significant LVEF Decline | 0 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With a Primary Cardiac Event During the Neoadjuvant Phase | Cardiac Death (Definite or Probable) | 0 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With a Primary Cardiac Event During the Neoadjuvant Phase | Any Primary Cardiac Event | 2 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With a Primary Cardiac Event During the Neoadjuvant Phase | Heart Failure and Significant LVEF Decline | 1 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With a Primary Cardiac Event During the Neoadjuvant Phase | Cardiac Death (Definite or Probable) | 1 Participants |
Secondary
Number of Participants With a Secondary Cardiac Event During the Adjuvant Phase
A secondary cardiac event is defined as asymptomatic or mildly symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II, defined as a left ventricular ejection fraction (LVEF) decrease of at least 10-percentage points below the baseline measurement to an absolute LVEF value of \<50% confirmed by a second assessment within approximately 3 weeks.
Time frame: From surgery until 28 days after the last dose of adjuvant treatment (42 weeks)
Population: Safety Population: includes all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With a Secondary Cardiac Event During the Adjuvant Phase | Any Secondary Cardiac Event | 15 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With a Secondary Cardiac Event During the Adjuvant Phase | Identified by Initial LVEF Assessment | 15 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With a Secondary Cardiac Event During the Adjuvant Phase | Confirmed by Second LVEF Assessment | 0 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With a Secondary Cardiac Event During the Adjuvant Phase | Any Secondary Cardiac Event | 8 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With a Secondary Cardiac Event During the Adjuvant Phase | Identified by Initial LVEF Assessment | 8 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With a Secondary Cardiac Event During the Adjuvant Phase | Confirmed by Second LVEF Assessment | 0 Participants |
Secondary
Number of Participants With a Secondary Cardiac Event During the Neoadjuvant Phase
A secondary cardiac event is defined as asymptomatic or mildly symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II, defined as a left ventricular ejection fraction (LVEF) decrease of at least 10-percentage points below the baseline measurement to an absolute LVEF value of \<50% confirmed by a second assessment within approximately 3 weeks.
Time frame: From first dose of study treatment until the completion of neoadjuvant therapy (24 weeks)
Population: Safety Population: includes all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With a Secondary Cardiac Event During the Neoadjuvant Phase | Any Secondary Cardiac Event | 4 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With a Secondary Cardiac Event During the Neoadjuvant Phase | Identified by Initial LVEF Assessment | 4 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With a Secondary Cardiac Event During the Neoadjuvant Phase | Confirmed by Second LVEF Assessment | 1 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With a Secondary Cardiac Event During the Neoadjuvant Phase | Confirmed by Second LVEF Assessment | 1 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With a Secondary Cardiac Event During the Neoadjuvant Phase | Any Secondary Cardiac Event | 1 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With a Secondary Cardiac Event During the Neoadjuvant Phase | Identified by Initial LVEF Assessment | 1 Participants |
Secondary
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study
Clinical laboratory tests were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest (worst) severity grade (according to NCI-CTCAE v4.0) post-baseline. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a medical intervention or a change in concomitant therapy. For a participant with multiple post-baseline abnormalities, only the highest (worst) grade for a given laboratory test is reported. 'Any Grade' indicates the total number of participants with a post-baseline abnormality of any grade for the specified test.
Time frame: From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months)
Population: Safety Population: includes all participants who received at least one dose of study medication. The number analyzed varies because it indicates all participants with a post-baseline laboratory value for a given test within the timeframe.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Albumin, Low - Grade 1 | 41 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGPT/ALT, High - Grade 2 | 18 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, Low - Grade 3 | 4 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGPT/ALT, High - Grade 3 | 9 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Alkaline Phosphatase, High - Grade 2 | 2 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGOT/AST, High - Any Grade | 149 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, Low - Grade 3 | 6 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGOT/AST, High - Grade 1 | 137 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, High - Any Grade | 25 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGOT/AST, High - Grade 2 | 7 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGOT/AST, High - Grade 3 | 5 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, High - Grade 1 | 19 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, Low - Any Grade | 45 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Creatinine, High - Grade 1 | 214 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, High - Grade 2 | 4 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Creatinine, High - Grade 2 | 9 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, Low - Grade 4 | 1 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Creatinine, High - Grade 3 | 2 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, High - Grade 3 | 0 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Glucose, Low - Any Grade | 23 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, Low - Grade 4 | 1 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Glucose, Low - Grade 1 | 20 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, High - Grade 4 | 2 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Glucose, Low - Grade 2 | 3 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, High - Any Grade | 24 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Glucose, High - Any Grade | 3 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Bilirubin, High - Any Grade | 24 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Glucose, High - Grade 3 | 3 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Alkaline Phosphatase, High - Grade 1 | 78 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Hemoglobin, Low - Any Grade | 233 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Bilirubin, High - Grade 1 | 16 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Hemoglobin, Low - Grade 1 | 129 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, High - Grade 1 | 17 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Hemoglobin, Low - Grade 2 | 93 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Bilirubin, High - Grade 2 | 7 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Hemoglobin, Low - Grade 3 | 11 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Albumin, Low - Grade 2 | 8 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Hemoglobin, High - Any Grade | 12 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Bilirubin, High - Grade 3 | 1 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Hemoglobin, High - Grade 1 | 12 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, High - Grade 2 | 7 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Lymphocytes, Abs., Low - Any Grade | 144 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Total Leukocyte Count, Low - Any Grade | 199 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Lymphocytes, Abs., Low - Grade 1 | 23 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Alkaline Phosphatase, High - Any Grade | 80 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Lymphocytes, Abs., Low - Grade 2 | 59 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Lymphocytes, Abs., Low - Grade 3 | 55 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Total Leukocyte Count, Low - Grade 1 | 57 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Lymphocytes, Abs., Low - Grade 4 | 7 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, High - Grade 3 | 0 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Lymphocytes, Abs., High - Any Grade | 4 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Total Leukocyte Count, Low - Grade 2 | 81 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Lymphocytes, Abs., High - Grade 2 | 4 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Albumin, Low - Grade 3 | 1 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Neutrophils, Total, Abs., Low - Any Grade | 110 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Total Leukocyte Count, Low - Grade 3 | 41 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Neutrophils, Total, Abs., Low - Grade 1 | 27 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, High - Grade 4 | 0 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Neutrophils, Total, Abs., Low - Grade 2 | 30 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Total Leukocyte Count, Low - Grade 4 | 20 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Neutrophils, Total, Abs., Low - Grade 3 | 17 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Albumin, Low - Any Grade | 50 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Neutrophils, Total, Abs., Low - Grade 4 | 36 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Total Leukocyte Count, High - Any Grade | 0 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Platelets, Low - Any Grade | 72 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, Low - Any Grade | 27 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Platelets, Low - Grade 1 | 68 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Total Leukocyte Count, High - Grade 1 | 0 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Platelets, Low - Grade 2 | 3 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Creatinine, High - Any Grade | 225 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Platelets, Low - Grade 3 | 1 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGPT/ALT, High - Any Grade | 172 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, Low - Grade 1 | 22 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, Low - Grade 2 | 38 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGPT/ALT, High - Grade 1 | 145 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, Low - Grade 2 | 28 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Alkaline Phosphatase, High - Any Grade | 71 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Alkaline Phosphatase, High - Grade 1 | 70 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Alkaline Phosphatase, High - Grade 2 | 1 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGOT/AST, High - Grade 2 | 3 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Lymphocytes, Abs., Low - Grade 2 | 68 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, High - Any Grade | 16 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Albumin, Low - Grade 2 | 5 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Albumin, Low - Any Grade | 39 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Albumin, Low - Grade 1 | 34 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, Low - Grade 3 | 11 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, Low - Grade 4 | 2 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, High - Any Grade | 32 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, High - Grade 1 | 26 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, High - Grade 2 | 3 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, High - Grade 3 | 2 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, High - Grade 4 | 1 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, Low - Any Grade | 33 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, Low - Grade 1 | 32 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, Low - Grade 3 | 0 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, Low - Grade 4 | 1 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, High - Grade 1 | 13 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, High - Grade 2 | 1 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, High - Grade 3 | 1 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Sodium, High - Grade 4 | 1 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Bilirubin, High - Any Grade | 22 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Bilirubin, High - Grade 1 | 17 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Bilirubin, High - Grade 2 | 5 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Bilirubin, High - Grade 3 | 0 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Total Leukocyte Count, Low - Any Grade | 203 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Total Leukocyte Count, Low - Grade 1 | 64 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Total Leukocyte Count, Low - Grade 2 | 78 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Total Leukocyte Count, Low - Grade 3 | 43 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Total Leukocyte Count, Low - Grade 4 | 18 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Total Leukocyte Count, High - Any Grade | 1 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Total Leukocyte Count, High - Grade 1 | 1 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGPT/ALT, High - Any Grade | 149 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGPT/ALT, High - Grade 1 | 132 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGPT/ALT, High - Grade 2 | 13 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGPT/ALT, High - Grade 3 | 4 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGOT/AST, High - Any Grade | 130 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGOT/AST, High - Grade 1 | 125 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | SGOT/AST, High - Grade 3 | 2 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Creatinine, High - Any Grade | 217 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Creatinine, High - Grade 1 | 204 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Creatinine, High - Grade 2 | 13 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Creatinine, High - Grade 3 | 0 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Glucose, Low - Any Grade | 22 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Glucose, Low - Grade 1 | 22 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Glucose, Low - Grade 2 | 0 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Glucose, High - Any Grade | 4 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Glucose, High - Grade 3 | 4 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Hemoglobin, Low - Any Grade | 223 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Hemoglobin, Low - Grade 1 | 139 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Hemoglobin, Low - Grade 2 | 77 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Hemoglobin, Low - Grade 3 | 7 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Hemoglobin, High - Any Grade | 6 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Hemoglobin, High - Grade 1 | 6 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Lymphocytes, Abs., Low - Any Grade | 150 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Lymphocytes, Abs., Low - Grade 1 | 22 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Lymphocytes, Abs., Low - Grade 3 | 56 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Lymphocytes, Abs., Low - Grade 4 | 4 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Lymphocytes, Abs., High - Any Grade | 3 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Lymphocytes, Abs., High - Grade 2 | 3 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Neutrophils, Total, Abs., Low - Any Grade | 114 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Neutrophils, Total, Abs., Low - Grade 1 | 42 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Neutrophils, Total, Abs., Low - Grade 2 | 23 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Neutrophils, Total, Abs., Low - Grade 3 | 24 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Neutrophils, Total, Abs., Low - Grade 4 | 25 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Platelets, Low - Any Grade | 67 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Platelets, Low - Grade 1 | 65 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Platelets, Low - Grade 2 | 2 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Platelets, Low - Grade 3 | 0 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Potassium, Low - Any Grade | 41 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline Over the Course of the Entire Study | Albumin, Low - Grade 3 | 0 Participants |
Secondary
Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment
Total pCR (tpCR) was defined as eradication of invasive disease in the breast and axilla; that is, ypT0/is ypN0, according to the local pathologists' assessment. Pathologic response to therapy was determined at the time of surgery. The tpCR rate is the percentage of participants in the ITT population who achieved a tpCR. Participants with missing data for tpCR (i.e., do not undergo surgery or have an invalid pCR assessment) were included in the analysis and classified as non-responders. Rates of tpCR were calculated in each treatment arm and were assessed using the difference between the Arm B: Pertuzumab and Trastuzumab FDC SC and the Arm A: Pertuzumab IV and Trastuzumab IV tpCR rates and corresponding 95% Clopper-Pearson confidence intervals (CIs). The difference between the tpCR rates along with corresponding 95% Hauck-Anderson CIs were calculated. The lower bound of the CI will reliably reflect the largest tpCR difference that can be considered unlikely.
Time frame: Following completion of surgery (up to 33 weeks)
Population: ITT Population: includes all enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment | 59.5 Percentage of participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment | 59.7 Percentage of participants |
95% CI: [-8.67, 8.97]
Secondary
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study
The adverse event (AE) severity grading scale for the NCI CTCAE v4.0 was used for assessing AE severity. Any AEs that were not specifically listed in the NCI CTCAE, v4.0 were graded per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. The terms severe and serious are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Time frame: From first dose of study treatment until 28 days after last dose of study treatment (up to 1 year, 6 months)
Population: Safety Population: includes all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Anaphylaxis and Hypersensitivity AEs, Grade ≥3 | 1 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Any Adverse Event (AE): Any Grade | 251 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | AE with Fatal Outcome (Grade 5) | 2 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Any AE: Grades 3 to 5 | 149 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Serious AE | 52 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Related Serious AE | 29 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Anaphylaxis and Hypersensitivity AEs, Any Grade | 3 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Infusion/Admin.-Related Reactions Within 24 hrs, Any Grade | 39 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Infusion/Admin.-Related Reactions Within 24 hrs, Grade ≥3 | 3 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Serious Rash/Skin Reactions, Any Grade | 0 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Serious Rash/Skin Reactions, Grade ≥3 | 0 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Diarrhoea, Any Grade | 149 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Diarrhoea, Grade ≥3 | 13 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Cardiac Dysfunction, Any Grade | 65 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Cardiac Dysfunction, Grade ≥3 | 12 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Interstitial Lung Disease, Any Grade | 3 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Interstitial Lung Disease, Grade ≥3 | 0 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Neutropenia/Febrile Neutropenia, Any Grade | 142 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Neutropenia/Febrile Neutropenia, Grade ≥3 | 92 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Serious Mucositis, Any Grade | 3 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Serious Mucositis, Grade ≥3 | 3 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Pregnancy- and Neonatal-Related AEs, Any Grade | 0 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | AE Leading to Study Drug Discontinuation | 32 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | AE Leading to HER2-Targeted Therapy Discontinuation | 15 Participants |
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | AE Leading to Any Chemotherapy Drug Discontinuation | 23 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Serious Mucositis, Any Grade | 3 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Cardiac Dysfunction, Any Grade | 52 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Any Adverse Event (AE): Any Grade | 248 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | AE Leading to Any Chemotherapy Drug Discontinuation | 14 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | AE with Fatal Outcome (Grade 5) | 2 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Cardiac Dysfunction, Grade ≥3 | 3 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Any AE: Grades 3 to 5 | 132 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Serious Mucositis, Grade ≥3 | 2 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Serious AE | 49 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Interstitial Lung Disease, Any Grade | 5 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Related Serious AE | 29 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | AE Leading to HER2-Targeted Therapy Discontinuation | 12 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Anaphylaxis and Hypersensitivity AEs, Any Grade | 3 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Interstitial Lung Disease, Grade ≥3 | 0 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Infusion/Admin.-Related Reactions Within 24 hrs, Any Grade | 54 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Pregnancy- and Neonatal-Related AEs, Any Grade | 0 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Infusion/Admin.-Related Reactions Within 24 hrs, Grade ≥3 | 0 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Neutropenia/Febrile Neutropenia, Any Grade | 123 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Serious Rash/Skin Reactions, Any Grade | 1 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Anaphylaxis and Hypersensitivity AEs, Grade ≥3 | 0 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Serious Rash/Skin Reactions, Grade ≥3 | 0 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Neutropenia/Febrile Neutropenia, Grade ≥3 | 82 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Diarrhoea, Any Grade | 153 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | AE Leading to Study Drug Discontinuation | 22 Participants |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), Over the Course of the Entire Study | Diarrhoea, Grade ≥3 | 16 Participants |