{"analyses":[{"ciLowerLimit":"1.24","ciNumSides":"TWO_SIDED","ciPctValue":"90","ciUpperLimit":"1.43","estimateComment":"The CtroughSC/CtroughIV geometric mean ratio was calculated as the SC dose of trastuzumab (Arm B) relative to the trastuzumab IV dose (Arm A).","groupDescription":"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).","groupIds":["OG000","OG001"],"nonInferiorityComment":"The null hypothesis could be rejected and non-inferiority concluded if the lower bound of the 90% confidence interval of the geometric mean ratio was ≥0.8. Non-inferiority was tested in hierarchical order after the primary outcome measure, to adjust for multiple statistical testing and control the type I error at one sided 5% significance level.","nonInferiorityType":"NON_INFERIORITY","paramType":"Geometric Mean Ratio","paramValue":"1.33"}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","spread":"34.7","value":"43.2"},{"groupId":"OG001","spread":"37.0","value":"57.5"}]}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"203"},{"groupId":"OG001","value":"206"}],"units":"Participants"}],"description":"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.","dispersionType":"Geometric Coefficient of Variation","groups":[{"description":"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.","id":"OG000","title":"Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy"},{"description":"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.","id":"OG001","title":"Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy"}],"paramType":"GEOMETRIC_MEAN","populationDescription":"Per Protocol PK Population: includes only participants who adhered to the pre-specified criteria for the schedule of pharmacokinetic assessments.","reportingStatus":"POSTED","timeFrame":"Pre-dose on Cycle 8, Day 1 (up to 21 weeks)","title":"Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8)","type":"SECONDARY","unitOfMeasure":"micrograms per milllilitre (μg/mL)"}