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A Study Evaluating Pertuzumab (Perjeta) Combined With Trastuzumab (Herceptin) and Standard Anthracycline-based Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced, Inflammatory, or Early-stage Breast Cancer

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ClinicalTrials.gov Identifier: NCT02132949
Recruitment Status : Active, not recruiting
First Posted : May 7, 2014
Results First Posted : April 13, 2017
Last Update Posted : April 29, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: 5-Fluorouracil
Drug: Cyclophosphamide
Drug: Docetaxel
Drug: Doxorubicin
Drug: Epirubicin
Drug: paclitaxel
Drug: Pertuzumab
Drug: Trastuzumab
Enrollment 401
Recruitment Details  
Pre-assignment Details A total of 401 participants were enrolled, 199 in Cohort A and 202 in Cohort B. One participant in Cohort B who was human epidermal growth factor receptor 2 (HER2) negative and was enrolled by error, was excluded. Hence, 199 participants were included in Cohort A and 201 participants in Cohort B.
Arm/Group Title Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab
Hide Arm/Group Description ddAC: dose dense doxorubicin and cyclophosphamide. Participants received doxorubicin 60 milligrams per square meter (mg/m^2; as an intravenous [IV] bolus over 3-5 minutes [min] or as an infusion over 15-30min) once in every 2 weeks (q2w) and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q2w, for 4 cycles followed by paclitaxel 80mg/m^2 IV infusion once weekly (qw) for 12 weeks. Pertuzumab 840 milligrams (mg) loading dose IV, then 420mg IV q3w and trastuzumab 8 milligrams per kilogram (mg/kg) loading dose, then 4mg/kg q3w were given along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study. FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants received 5-fluorouracil 500mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, epirubicin 100mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m^2 in Cycle 5, then 100mg/m^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
Period Title: Neoadjuvant Treatment Period
Started 199 [1] 201
No Treatment 1 3
Completed 182 189
Not Completed 17 12
Reason Not Completed
Early surgery             4             3
Reason unspecified             3             1
Lack of Efficacy             0             1
Physician Decision             2             0
Withdrawal by Subject             1             0
Disease Progression             1             1
Adverse Event             6             3
Withdrew prior to treatment             0             3
[1]
A participant enrolled in Cohort B received Cohort A treatment, hence counted under Cohort A.
Period Title: Adjuvant Treatment Period
Started 178 [1] 190 [2]
Completed 29 23
Not Completed 149 167
Reason Not Completed
Adverse Event             4             6
Reason unspecified             0             1
Disease Progression             0             1
Disease Relapse             0             1
Physician Decision             1             0
Withdrawal by Subject             1             1
Protocol Deviation             1             0
Ongoing in Adjuvant Treatment             142             157
[1]
At clinical cutoff (03 March 2016), some participants had not yet received adjuvant treatment.
[2]
Includes a participant who did not complete neoadjuvant treatment but started adjuvant treatment.
Arm/Group Title Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab Total
Hide Arm/Group Description ddAC: dose dense doxorubicin and cyclophosphamide. Participants received doxorubicin 60 milligrams per square meter (mg/m^2; as an intravenous [IV] bolus over 3-5 minutes [min] or as an infusion over 15-30min) once in every 2 weeks (q2w) and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q2w, for 4 cycles followed by paclitaxel 80mg/m^2 IV infusion once weekly (qw) for 12 weeks. Pertuzumab 840 milligrams (mg) loading dose IV, then 420mg IV q3w and trastuzumab 8 milligrams per kilogram (mg/kg) loading dose, then 4mg/kg q3w were given along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study. FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants received 5-fluorouracil 500mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, epirubicin 100mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m^2 in Cycle 5, then 100mg/m^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study. Total of all reporting groups
Overall Number of Baseline Participants 199 201 400
Hide Baseline Analysis Population Description
Intent to treat (ITT) population included all participants who were enrolled regardless of whether they received any study treatment. One participant in Cohort B who was HER2 negative and was enrolled by error was excluded from the ITT population.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 199 participants 201 participants 400 participants
49.8  (11.7) 49.5  (11.5) 49.6  (11.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 199 participants 201 participants 400 participants
Female
199
 100.0%
200
  99.5%
399
  99.8%
Male
0
   0.0%
1
   0.5%
1
   0.3%
1.Primary Outcome
Title Percentage of Participants With New York Heart Association (NYHA) Class III and IV Heart Failure During the Neoadjuvant Treatment Period
Hide Description Symptomatic left ventricular systolic dysfunction (LVSD) is defined as heart failure. NYHA classifies participants' heart failure condition based on the participant's symptoms. Class III: marked limitation of the physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. 95 percent (%) confidence intervals (CIs) are calculated with the use of the Clopper-Pearson method.
Time Frame Baseline to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis population included all participants who received any amount of study drug.
Arm/Group Title ddAC, Paclitaxel, Pertuzumab, Trastuzumab FEC, Docetaxel, Pertuzumab, Trastuzumab
Hide Arm/Group Description:
ddAC: dose dense doxorubicin and cyclophosphamide. Participants received doxorubicin 60 mg/m^2 (as an IV bolus over 3-5min or as an infusion over 15-30min) q2w and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q2w, for 4 cycles followed by paclitaxel 80mg/m^2 IV infusion qw for 12 weeks. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants received 5-fluorouracil 500mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, epirubicin 100mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m^2 in Cycle 5, then 100mg/m^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
Overall Number of Participants Analyzed 199 198
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
1.5
(0.31 to 4.34)
0
(0.00 to 1.85)
2.Primary Outcome
Title Percentage of Participants With Drop in Left Ventricular Ejection Fraction (LVEF) of at Least 10 Percentage Points From Baseline and to Below 50% During the Neoadjuvant Treatment Period
Hide Description A confirmed event was defined as at least two consecutive readings of declines in LVEF. 95% CIs are calculated with the use of the Clopper-Pearson method.
Time Frame Baseline to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis population
Arm/Group Title ddAC, Paclitaxel, Pertuzumab, Trastuzumab FEC, Docetaxel, Pertuzumab, Trastuzumab
Hide Arm/Group Description:
ddAC: dose dense doxorubicin and cyclophosphamide. Participants received doxorubicin 60 mg/m^2 (as an IV bolus over 3-5min or as an infusion over 15-30min) q2w and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q2w, for 4 cycles followed by paclitaxel 80mg/m^2 IV infusion qw for 12 weeks. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants received 5-fluorouracil 500mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, epirubicin 100mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m^2 in Cycle 5, then 100mg/m^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
Overall Number of Participants Analyzed 199 198
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
6.5
(3.5 to 10.9)
2.0
(0.6 to 5.1)
3.Secondary Outcome
Title Percentage of Participants With NYHA Class III and IV Heart Failure During the Adjuvant Treatment Period at Primary Completion Date (03 March 2016)
Hide Description LVSD is defined as heart failure. NYHA classifies participants' heart failure condition based on the participant's symptoms. Class III: marked limitation of the physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. 95% CIs was calculated with the use of the Clopper-Pearson method.
Time Frame Cycle 9 to Cycle 21 (cycle length=3 weeks; up to approximately 8 months) up to clinical cut-off date, 03 March 2016 (Month 20)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis population who have started adjuvant treatment and were analyzable at the clinical cut-off date (03 March 2016).
Arm/Group Title ddAC, Paclitaxel, Pertuzumab, Trastuzumab FEC, Docetaxel, Pertuzumab, Trastuzumab
Hide Arm/Group Description:
ddAC: dose dense doxorubicin and cyclophosphamide. Participants received doxorubicin 60 mg/m^2 (as an IV bolus over 3-5min or as an infusion over 15-30min) q2w and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q2w, for 4 cycles followed by paclitaxel 80mg/m^2 IV infusion qw for 12 weeks. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants received 5-fluorouracil 500mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, epirubicin 100mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m^2 in Cycle 5, then 100mg/m^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
Overall Number of Participants Analyzed 178 190
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0
(0.00 to 2.05)
0.5
(0.01 to 2.90)
4.Secondary Outcome
Title Percentage of Participants With Drop in LVEF of at Least 10 Points From Baseline and to Below 50% During the Adjuvant Treatment Period at Primary Completion Date (03 March 2016)
Hide Description A confirmed event was defined as at least two consecutive readings of declines in LVEF. 95% CIs was calculated with the use of the Clopper-Pearson method.
Time Frame Cycle 9 to Cycle 21 (cycle length=3 weeks; up to approximately 8 months) up to clinical cut-off date, 03 March 2016 (Month 20)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis population who have started adjuvant treatment and were analyzable at the clinical cut-off date (03 March 2016).
Arm/Group Title ddAC, Paclitaxel, Pertuzumab, Trastuzumab FEC, Docetaxel, Pertuzumab, Trastuzumab
Hide Arm/Group Description:
ddAC: dose dense doxorubicin and cyclophosphamide. Participants received doxorubicin 60 mg/m^2 (as an IV bolus over 3-5min or as an infusion over 15-30min) q2w and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q2w, for 4 cycles followed by paclitaxel 80mg/m^2 IV infusion qw for 12 weeks. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants received 5-fluorouracil 500mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, epirubicin 100mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m^2 in Cycle 5, then 100mg/m^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
Overall Number of Participants Analyzed 178 190
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
5.1
(2.3 to 9.4)
6.8
(3.7 to 11.4)
5.Secondary Outcome
Title Percentage of Participants With NYHA Class III and IV Heart Failure at the End of Study
Hide Description LVSD is defined as heart failure. NYHA classifies participants' heart failure condition based on the participant's symptoms. Class III: marked limitation of the physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. 95% CIs will be calculated with the use of the Clopper-Pearson method.
Time Frame Baseline up to approximately 6.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Because the study is ongoing, results of this end point are anticipated by December 2020.
Arm/Group Title ddAC, Paclitaxel, Pertuzumab, Trastuzumab FEC, Docetaxel, Pertuzumab, Trastuzumab
Hide Arm/Group Description:
ddAC: dose dense doxorubicin and cyclophosphamide. Participants received doxorubicin 60 mg/m^2 (as an IV bolus over 3-5min or as an infusion over 15-30min) q2w and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q2w, for 4 cycles followed by paclitaxel 80mg/m^2 IV infusion qw for 12 weeks. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants received 5-fluorouracil 500mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, epirubicin 100mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m^2 in Cycle 5, then 100mg/m^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Percentage of Participants With Drop in LVEF of at Least 10 Points From Baseline and to Below 50% at End of Study
Hide Description A confirmed event was defined as at least two consecutive readings of declines in LVEF. 95% CIs will be calculated with the use of the Clopper-Pearson method.
Time Frame Baseline up to approximately 6.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Because the study is ongoing, results of this end point are anticipated by December 2020.
Arm/Group Title ddAC, Paclitaxel, Pertuzumab, Trastuzumab FEC, Docetaxel, Pertuzumab, Trastuzumab
Hide Arm/Group Description:
ddAC: dose dense doxorubicin and cyclophosphamide. Participants received doxorubicin 60 mg/m^2 (as an IV bolus over 3-5min or as an infusion over 15-30min) q2w and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q2w, for 4 cycles followed by paclitaxel 80mg/m^2 IV infusion qw for 12 weeks. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants received 5-fluorouracil 500mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, epirubicin 100mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m^2 in Cycle 5, then 100mg/m^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Pertuzumab
Hide Description [Not Specified]
Time Frame Screening then prior to pertuzumab infusion (Hour 0) in Cycles 5, 14, 18 thereafter anytime between Cycle 8 Day 21 and surgery, up to treatment completion visit (cycle length=2-3 weeks; up to approximately 6.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, "number of participants analyzed" include those who were evaluable for the outcome.
Arm/Group Title ddAC, Paclitaxel, Pertuzumab, Trastuzumab FEC, Docetaxel, Pertuzumab, Trastuzumab
Hide Arm/Group Description:
ddAC: dose dense doxorubicin and cyclophosphamide. Participants received doxorubicin 60 mg/m^2 (as an IV bolus over 3-5min or as an infusion over 15-30min) q2w and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q2w, for 4 cycles followed by paclitaxel 80mg/m^2 IV infusion qw for 12 weeks. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants received 5-fluorouracil 500mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, epirubicin 100mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m^2 in Cycle 5, then 100mg/m^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
Overall Number of Participants Analyzed 186 197
Measure Type: Number
Unit of Measure: percentage of participants
0.0 0.5
8.Secondary Outcome
Title Percentage of Participants With Total Pathological Complete Response (tpCR) Evaluated at the Time of Surgery Based on Local Pathologist's Assessment After Surgery
Hide Description tpCR is defined as the absence of any residual invasive cancer in the breast and the absence of any metastatic cells in the regional lymph nodes.
Time Frame 24 weeks after neoadjuvant therapy (Post 8 cycles of neo-adjuvant therapy [cycle length=2¬3 weeks])
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title ddAC, Paclitaxel, Pertuzumab, Trastuzumab FEC, Docetaxel, Pertuzumab, Trastuzumab
Hide Arm/Group Description:
ddAC: dose dense doxorubicin and cyclophosphamide. Participants received doxorubicin 60 mg/m^2 (as an IV bolus over 3-5min or as an infusion over 15-30min) q2w and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q2w, for 4 cycles followed by paclitaxel 80mg/m^2 IV infusion qw for 12 weeks. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants received 5-fluorouracil 500mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, epirubicin 100mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m^2 in Cycle 5, then 100mg/m^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
Overall Number of Participants Analyzed 199 201
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
61.8
(54.67 to 68.59)
60.7
(53.58 to 67.49)
9.Secondary Outcome
Title Percentage of Participants With Clinical Response as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 During the Neoadjuvant Treatment Period
Hide Description Clinical response was classified as either complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). CR: disappearance of all target lesions; PR: at least a 30% decrease in the sum of the longest diameter compared to Baseline. SD: neither sufficient shrinkage to qualify for PR nor sufficient (20%) increase to qualify for disease progression, in addition to no new target lesions. PD: at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions. 95% CIs are calculated with the use of the Clopper-Pearson method.
Time Frame Baseline until disease progression or death due to any cause up to 24 weeks (assessed on Day 1 of Cycles 1-8 [cycle length=2-3 weeks])
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Hide Analysis Population Description
ITT population
Arm/Group Title ddAC, Paclitaxel, Pertuzumab, Trastuzumab FEC, Docetaxel, Pertuzumab, Trastuzumab
Hide Arm/Group Description:
ddAC: dose dense doxorubicin and cyclophosphamide. Participants received doxorubicin 60 mg/m^2 (as an IV bolus over 3-5min or as an infusion over 15-30min) q2w and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q2w, for 4 cycles followed by paclitaxel 80mg/m^2 IV infusion qw for 12 weeks. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants received 5-fluorouracil 500mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, epirubicin 100mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m^2 in Cycle 5, then 100mg/m^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
Overall Number of Participants Analyzed 199 201
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Complete response
39.7
(32.85 to 46.86)
23.9
(18.16 to 30.39)
Partial response
27.6
(21.55 to 34.41)
36.3
(29.67 to 43.38)
Stable disease
7.0
(3.90 to 11.52)
10.0
(6.18 to 14.95)
Progressive disease
0.5
(0.01 to 2.77)
1.0
(0.12 to 3.55)
10.Secondary Outcome
Title Event-Free Survival Determined by the Investigator According to RECIST v1.1
Hide Description EFS is defined as the time from enrollment to the first occurrence of progressive disease, relapse, or death from any cause. PD: at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions.
Time Frame Baseline until disease progression or death due to any cause up to approximately 6.5 years (assessed on Day 1 of Cycles 1-8 [cycle length=2-3 weeks] and every 3 months thereafter until study completion or early termination)
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Hide Analysis Population Description
Because the study is ongoing, results of this end point are anticipated by December 2020.
Arm/Group Title ddAC, Paclitaxel, Pertuzumab, Trastuzumab FEC, Docetaxel, Pertuzumab, Trastuzumab
Hide Arm/Group Description:
ddAC: dose dense doxorubicin and cyclophosphamide. Participants received doxorubicin 60 mg/m^2 (as an IV bolus over 3-5min or as an infusion over 15-30min) q2w and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q2w, for 4 cycles followed by paclitaxel 80mg/m^2 IV infusion qw for 12 weeks. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants received 5-fluorouracil 500mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, epirubicin 100mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m^2 in Cycle 5, then 100mg/m^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Invasive Disease Free Survival (iDFS) Determined by the Investigator According to RECIST v1.1
Hide Description iDFS is defined as the time from the first date of no disease (the date of surgery) to the first documentation of progressive invasive disease, relapse, or death. PD: at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions.
Time Frame Baseline until disease progression or death due to any cause up to approximately 6.5 years (assessed on Day 1 of Cycles 1-8 [cycle length=2-3 weeks] and every 3 months thereafter until study completion or early termination)
Hide Outcome Measure Data
Hide Analysis Population Description
Because the study is ongoing, results of this end point are anticipated by December 2020.
Arm/Group Title ddAC, Paclitaxel, Pertuzumab, Trastuzumab FEC, Docetaxel, Pertuzumab, Trastuzumab
Hide Arm/Group Description:
ddAC: dose dense doxorubicin and cyclophosphamide. Participants received doxorubicin 60 mg/m^2 (as an IV bolus over 3-5min or as an infusion over 15-30min) q2w and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q2w, for 4 cycles followed by paclitaxel 80mg/m^2 IV infusion qw for 12 weeks. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants received 5-fluorouracil 500mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, epirubicin 100mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m^2 in Cycle 5, then 100mg/m^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from enrollment to death from any cause.
Time Frame Baseline up to death (approximately 6.5 years)
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Hide Analysis Population Description
Because the study is ongoing, results of this end point are anticipated by December 2020.
Arm/Group Title ddAC, Paclitaxel, Pertuzumab, Trastuzumab FEC, Docetaxel, Pertuzumab, Trastuzumab
Hide Arm/Group Description:
ddAC: dose dense doxorubicin and cyclophosphamide. Participants received doxorubicin 60 mg/m^2 (as an IV bolus over 3-5min or as an infusion over 15-30min) q2w and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q2w, for 4 cycles followed by paclitaxel 80mg/m^2 IV infusion qw for 12 weeks. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants received 5-fluorouracil 500mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, epirubicin 100mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m^2 in Cycle 5, then 100mg/m^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Baseline up to 24 weeks
Adverse Event Reporting Description Safety analysis population was considered for analysis. Reported adverse events data covers the safety information during the neoadjuvant period.
 
Arm/Group Title Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab
Hide Arm/Group Description ddAC: dose dense doxorubicin and cyclophosphamide. Participants received doxorubicin 60 milligrams per square meter (mg/m^2; as an intravenous [IV] bolus over 3-5 minutes [min] or as an infusion over 15-30min) once in every 2 weeks (q2w) and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q2w, for 4 cycles followed by paclitaxel 80mg/m^2 IV infusion once weekly (qw) for 12 weeks. Pertuzumab 840 milligrams (mg) loading dose IV, then 420mg IV q3w and trastuzumab 8 milligrams per kilogram (mg/kg) loading dose, then 4mg/kg q3w were given along with paclitaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study. FEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants received 5-fluorouracil 500mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, epirubicin 100mg/m^2 (as an IV bolus over 3-5min or as an infusion over 3-5min, in accordance with local policy) q3w, and cyclophosphamide 600mg/m^2 (IV bolus over 3-5min or as an infusion, in accordance with local policy) q3w for 4 cycles, followed by docetaxel (with starting dose of 75mg/m^2 in Cycle 5, then 100mg/m^2 for Cycles 6-8) q3w for 4 cycles. Pertuzumab 840 mg loading dose IV, then 420mg IV q3w and trastuzumab 8 mg/kg loading dose, then 4mg/kg q3w were given along with doectaxel for 4 cycles (8 cycles of chemotherapy in total prior to surgery). Following surgery, participants received further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
All-Cause Mortality
Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab
Affected / at Risk (%) Affected / at Risk (%)
Total   45/199 (22.61%)   52/198 (26.26%) 
Blood and lymphatic system disorders     
Agranulocytosis * 1  1/199 (0.50%)  0/198 (0.00%) 
Bone marrow failure * 1  1/199 (0.50%)  0/198 (0.00%) 
Febrile neutropenia * 1  12/199 (6.03%)  27/198 (13.64%) 
Leukopenia * 1  1/199 (0.50%)  0/198 (0.00%) 
Neutropenia * 1  2/199 (1.01%)  2/198 (1.01%) 
Pancytopenia * 1  0/199 (0.00%)  1/198 (0.51%) 
Cardiac disorders     
Atrial flutter * 1  1/199 (0.50%)  0/198 (0.00%) 
Cardiac failure * 1  2/199 (1.01%)  0/198 (0.00%) 
Cardiac failure congestive * 1  1/199 (0.50%)  0/198 (0.00%) 
Cardiogenic shock * 1  1/199 (0.50%)  0/198 (0.00%) 
Myocardial ischaemia * 1  1/199 (0.50%)  0/198 (0.00%) 
Gastrointestinal disorders     
Diarrhoea * 1  1/199 (0.50%)  11/198 (5.56%) 
Neutropenic colitis * 1  1/199 (0.50%)  0/198 (0.00%) 
Odynophagia * 1  1/199 (0.50%)  0/198 (0.00%) 
Pancreatitis * 1  1/199 (0.50%)  0/198 (0.00%) 
Pancreatitis acute * 1  1/199 (0.50%)  0/198 (0.00%) 
Proctalgia * 1  1/199 (0.50%)  0/198 (0.00%) 
Vomiting * 1  0/199 (0.00%)  1/198 (0.51%) 
General disorders     
General physical health deterioration * 1  1/199 (0.50%)  0/198 (0.00%) 
Mucosal inflammation * 1  0/199 (0.00%)  1/198 (0.51%) 
Pyrexia * 1  1/199 (0.50%)  4/198 (2.02%) 
Systemic inflammatory response syndrome * 1  0/199 (0.00%)  1/198 (0.51%) 
Hepatobiliary disorders     
Cholelithiasis * 1  0/199 (0.00%)  1/198 (0.51%) 
Immune system disorders     
Anaphylactic reaction * 1  0/199 (0.00%)  1/198 (0.51%) 
Hypersensitivity * 1  1/199 (0.50%)  0/198 (0.00%) 
Infections and infestations     
Cellulitis * 1  2/199 (1.01%)  0/198 (0.00%) 
Device related infection * 1  4/199 (2.01%)  2/198 (1.01%) 
Febrile infection * 1  1/199 (0.50%)  0/198 (0.00%) 
Gastrointestinal infection * 1  1/199 (0.50%)  0/198 (0.00%) 
Lower respiratory tract infection * 1  1/199 (0.50%)  0/198 (0.00%) 
Neutropenic sepsis * 1  0/199 (0.00%)  7/198 (3.54%) 
Peritonitis * 1  0/199 (0.00%)  1/198 (0.51%) 
Pneumonia * 1  2/199 (1.01%)  1/198 (0.51%) 
Pseudomonal bacteraemia * 1  0/199 (0.00%)  1/198 (0.51%) 
Pyelonephritis * 1  1/199 (0.50%)  0/198 (0.00%) 
Urinary tract infection * 1  2/199 (1.01%)  0/198 (0.00%) 
Wound infection * 1  0/199 (0.00%)  1/198 (0.51%) 
Injury, poisoning and procedural complications     
Infusion related reaction * 1  0/199 (0.00%)  2/198 (1.01%) 
Post procedural haematoma * 1  0/199 (0.00%)  1/198 (0.51%) 
Seroma * 1  1/199 (0.50%)  1/198 (0.51%) 
Investigations     
Alanine aminotransferase increased * 1  1/199 (0.50%)  0/198 (0.00%) 
Ejection fraction decreased * 1  3/199 (1.51%)  0/198 (0.00%) 
Neutrophil count decreased * 1  0/199 (0.00%)  1/198 (0.51%) 
Transaminases increased * 1  1/199 (0.50%)  0/198 (0.00%) 
White blood cell count decreased * 1  1/199 (0.50%)  0/198 (0.00%) 
Metabolism and nutrition disorders     
Dehydration * 1  1/199 (0.50%)  0/198 (0.00%) 
Nervous system disorders     
Presyncope * 1  0/199 (0.00%)  1/198 (0.51%) 
Syncope * 1  1/199 (0.50%)  0/198 (0.00%) 
Psychiatric disorders     
Depression * 1  1/199 (0.50%)  0/198 (0.00%) 
Renal and urinary disorders     
Acute kidney injury * 1  2/199 (1.01%)  0/198 (0.00%) 
Reproductive system and breast disorders     
Breast haematoma * 1  0/199 (0.00%)  1/198 (0.51%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  2/199 (1.01%)  1/198 (0.51%) 
Pneumonitis * 1  1/199 (0.50%)  0/198 (0.00%) 
Pulmonary embolism * 1  2/199 (1.01%)  0/198 (0.00%) 
Skin and subcutaneous tissue disorders     
Erythema multiforme * 1  1/199 (0.50%)  0/198 (0.00%) 
Skin necrosis * 1  0/199 (0.00%)  1/198 (0.51%) 
Surgical and medical procedures     
Mastectomy * 1  0/199 (0.00%)  1/198 (0.51%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (19.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab
Affected / at Risk (%) Affected / at Risk (%)
Total   197/199 (98.99%)   198/198 (100.00%) 
Blood and lymphatic system disorders     
Anaemia * 1  54/199 (27.14%)  60/198 (30.30%) 
Neutropenia * 1  42/199 (21.11%)  31/198 (15.66%) 
Eye disorders     
Dry eye * 1  12/199 (6.03%)  10/198 (5.05%) 
Lacrimation increased * 1  18/199 (9.05%)  36/198 (18.18%) 
Vision blurred * 1  13/199 (6.53%)  1/198 (0.51%) 
Gastrointestinal disorders     
Abdominal pain * 1  10/199 (5.03%)  20/198 (10.10%) 
Abdominal pain upper * 1  12/199 (6.03%)  26/198 (13.13%) 
Constipation * 1  69/199 (34.67%)  76/198 (38.38%) 
Diarrhoea * 1  132/199 (66.33%)  130/198 (65.66%) 
Dry mouth * 1  9/199 (4.52%)  14/198 (7.07%) 
Dyspepsia * 1  38/199 (19.10%)  32/198 (16.16%) 
Gastrooesophageal reflux disease * 1  23/199 (11.56%)  4/198 (2.02%) 
Haemorrhoids * 1  16/199 (8.04%)  17/198 (8.59%) 
Mouth ulceration * 1  5/199 (2.51%)  12/198 (6.06%) 
Nausea * 1  141/199 (70.85%)  137/198 (69.19%) 
Stomatitis * 1  49/199 (24.62%)  54/198 (27.27%) 
Vomiting * 1  45/199 (22.61%)  69/198 (34.85%) 
General disorders     
Asthenia * 1  37/199 (18.59%)  82/198 (41.41%) 
Chills * 1  13/199 (6.53%)  2/198 (1.01%) 
Fatigue * 1  116/199 (58.29%)  76/198 (38.38%) 
Influenza like illness * 1  2/199 (1.01%)  15/198 (7.58%) 
Mucosal inflammation * 1  43/199 (21.61%)  74/198 (37.37%) 
Oedema peripheral * 1  18/199 (9.05%)  24/198 (12.12%) 
Pain * 1  14/199 (7.04%)  4/198 (2.02%) 
Pyrexia * 1  29/199 (14.57%)  31/198 (15.66%) 
Infections and infestations     
Conjunctivitis * 1  8/199 (4.02%)  16/198 (8.08%) 
Nasopharyngitis * 1  14/199 (7.04%)  17/198 (8.59%) 
Oral candidiasis * 1  1/199 (0.50%)  11/198 (5.56%) 
Rhinitis * 1  6/199 (3.02%)  14/198 (7.07%) 
Upper respiratory tract infection * 1  14/199 (7.04%)  4/198 (2.02%) 
Urinary tract infection * 1  19/199 (9.55%)  4/198 (2.02%) 
Injury, poisoning and procedural complications     
Infusion related reaction * 1  31/199 (15.58%)  23/198 (11.62%) 
Procedural pain * 1  15/199 (7.54%)  8/198 (4.04%) 
Investigations     
Alanine aminotransferase increased * 1  14/199 (7.04%)  10/198 (5.05%) 
Aspartate aminotransferase increased * 1  14/199 (7.04%)  8/198 (4.04%) 
Ejection fraction decreased * 1  11/199 (5.53%)  7/198 (3.54%) 
Lymphocyte count Decreased * 1  10/199 (5.03%)  0/198 (0.00%) 
Neutrophil count decreased * 1  17/199 (8.54%)  17/198 (8.59%) 
Weight decreased * 1  13/199 (6.53%)  8/198 (4.04%) 
White blood cell count decreased * 1  21/199 (10.55%)  5/198 (2.53%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  39/199 (19.60%)  45/198 (22.73%) 
Dehydration * 1  10/199 (5.03%)  1/198 (0.51%) 
Hypokalaemia * 1  14/199 (7.04%)  5/198 (2.53%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  39/199 (19.60%)  42/198 (21.21%) 
Back pain * 1  20/199 (10.05%)  17/198 (8.59%) 
Bone pain * 1  23/199 (11.56%)  9/198 (4.55%) 
Muscle spasms * 1  15/199 (7.54%)  2/198 (1.01%) 
Musculoskeletal pain * 1  9/199 (4.52%)  10/198 (5.05%) 
Myalgia * 1  40/199 (20.10%)  66/198 (33.33%) 
Pain in extremity * 1  20/199 (10.05%)  15/198 (7.58%) 
Nervous system disorders     
Dizziness * 1  23/199 (11.56%)  15/198 (7.58%) 
Dysgeusia * 1  39/199 (19.60%)  38/198 (19.19%) 
Headache * 1  60/199 (30.15%)  28/198 (14.14%) 
Hypoaesthesia * 1  11/199 (5.53%)  7/198 (3.54%) 
Neuropathy peripheral * 1  46/199 (23.12%)  26/198 (13.13%) 
Paraesthesia * 1  29/199 (14.57%)  18/198 (9.09%) 
Peripheral sensory neuropathy * 1  38/199 (19.10%)  15/198 (7.58%) 
Psychiatric disorders     
Anxiety * 1  17/199 (8.54%)  9/198 (4.55%) 
Depression * 1  12/199 (6.03%)  4/198 (2.02%) 
Insomnia * 1  37/199 (18.59%)  25/198 (12.63%) 
Renal and urinary disorders     
Dysuria * 1  13/199 (6.53%)  2/198 (1.01%) 
Pollakiuria * 1  12/199 (6.03%)  2/198 (1.01%) 
Reproductive system and breast disorders     
Breast pain * 1  13/199 (6.53%)  12/198 (6.06%) 
Vulvovaginal dryness * 1  12/199 (6.03%)  4/198 (2.02%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  40/199 (20.10%)  17/198 (8.59%) 
Dyspnoea * 1  28/199 (14.07%)  29/198 (14.65%) 
Epistaxis * 1  50/199 (25.13%)  37/198 (18.69%) 
Nasal congestion * 1  15/199 (7.54%)  2/198 (1.01%) 
Oropharyngeal pain * 1  20/199 (10.05%)  15/198 (7.58%) 
Rhinorrhoea * 1  12/199 (6.03%)  19/198 (9.60%) 
Upper-airway cough syndrome * 1  11/199 (5.53%)  0/198 (0.00%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  124/199 (62.31%)  116/198 (58.59%) 
Dermatitis acneiform * 1  11/199 (5.53%)  6/198 (3.03%) 
Dry skin * 1  27/199 (13.57%)  19/198 (9.60%) 
Erythema * 1  3/199 (1.51%)  11/198 (5.56%) 
Nail discolouration * 1  29/199 (14.57%)  3/198 (1.52%) 
Nail disorder * 1  14/199 (7.04%)  19/198 (9.60%) 
Onycholysis * 1  11/199 (5.53%)  9/198 (4.55%) 
Onychomadesis * 1  18/199 (9.05%)  1/198 (0.51%) 
Palmar-plantar erythrodysaesthesia syndrome * 1  11/199 (5.53%)  20/198 (10.10%) 
Pruritus * 1  15/199 (7.54%)  16/198 (8.08%) 
Rash * 1  28/199 (14.07%)  21/198 (10.61%) 
Rash maculo-papular * 1  16/199 (8.04%)  1/198 (0.51%) 
Skin hyperpigmentation * 1  10/199 (5.03%)  3/198 (1.52%) 
Vascular disorders     
Hot flush * 1  38/199 (19.10%)  26/198 (13.13%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (19.0)
The study is still ongoing and the results are based on the primary analysis (clinical cut-off date of 03 March 2016). Full data from the adjuvant and treatment-free follow-up periods are anticipated by December 2020.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor’s intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02132949     History of Changes
Other Study ID Numbers: WO29217
2014-000156-28 ( EudraCT Number )
First Submitted: May 6, 2014
First Posted: May 7, 2014
Results First Submitted: March 1, 2017
Results First Posted: April 13, 2017
Last Update Posted: April 29, 2019