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NCT03493854 · OUTCOME

Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8)

A Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Participants With HER2-Positive Early Breast Cancer · Source last updated 2024-06-26

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Measure
GEOMETRIC_MEAN
Unit
micrograms per milllilitre (μg/mL)
Interval / dispersion
Geometric Coefficient of Variation
Time frame
Pre-dose on Cycle 8, Day 1 (up to 21 weeks)

What was measured

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.

Analysis population: Per Protocol PK Population: includes only participants who adhered to the pre-specified criteria for the schedule of pharmacokinetic assessments.

Groups in this outcome

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.

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.

Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.

Analysis denominator · Participants

GroupSource count
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy203
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy206

Reported measurements

Source class 1
Values in micrograms per milllilitre (μg/mL) · Interval/dispersion: Geometric Coefficient of Variation
GroupValueSpreadLowerUpperComment
Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy43.234.7Not reportedNot reportedNot reported
Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy57.537.0Not reportedNot reportedNot reported

Source statistical analyses

Group order, estimate direction, methods and comments are retained. No treatment ranking is inferred.

  1. ci Lower Limit
    1.24
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    90
    ci Upper Limit
    1.43
    estimate Comment
    The CtroughSC/CtroughIV geometric mean ratio was calculated as the SC dose of trastuzumab (Arm B) relative to the trastuzumab IV dose (Arm A).
    group Description
    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).
    group Ids
    1. OG000
    2. OG001
    non Inferiority Comment
    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.
    non Inferiority Type
    NON_INFERIORITY
    param Type
    Geometric Mean Ratio
    param Value
    1.33
Complete source fields
analyses
  1. ci Lower Limit
    1.24
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    90
    ci Upper Limit
    1.43
    estimate Comment
    The CtroughSC/CtroughIV geometric mean ratio was calculated as the SC dose of trastuzumab (Arm B) relative to the trastuzumab IV dose (Arm A).
    group Description
    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).
    group Ids
    1. OG000
    2. OG001
    non Inferiority Comment
    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.
    non Inferiority Type
    NON_INFERIORITY
    param Type
    Geometric Mean Ratio
    param Value
    1.33
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        spread
        34.7
        value
        43.2
      2. group Id
        OG001
        spread
        37.0
        value
        57.5
denoms
  1. counts
    1. group Id
      OG000
      value
      203
    2. group Id
      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.
dispersion Type
Geometric Coefficient of Variation
groups
  1. 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
  2. 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
param Type
GEOMETRIC_MEAN
population Description
Per Protocol PK Population: includes only participants who adhered to the pre-specified criteria for the schedule of pharmacokinetic assessments.
reporting Status
POSTED
time Frame
Pre-dose on Cycle 8, Day 1 (up to 21 weeks)
title
Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8)
type
SECONDARY
unit Of Measure
micrograms per milllilitre (μg/mL)

Download exact source JSON → · Snapshot ctgov-results-191f4516d4760045304b24a0

Preserved source evidence · Not medical advice