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A Study of Trastuzumab Emtansine (Kadcyla) Plus Pertuzumab (Perjeta) Following Anthracyclines in Comparison With Trastuzumab (Herceptin) Plus Pertuzumab and a Taxane Following Anthracyclines as Adjuvant Therapy in Participants With Operable HER2-Positive Primary Breast Cancer

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ClinicalTrials.gov Identifier: NCT01966471
Recruitment Status : Active, not recruiting
First Posted : October 21, 2013
Results First Posted : January 12, 2021
Last Update Posted : June 28, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: Trastuzumab Emtansine
Drug: Trastuzumab
Drug: Pertuzumab
Drug: Paclitaxel
Drug: Epirubicin
Drug: Doxorubicin
Drug: Docetaxel
Drug: Cyclophosphamide
Drug: 5-Fluorouracil
Enrollment 1846
Recruitment Details The study was conducted at 288 centers in 36 countries.
Pre-assignment Details Randomization was stratified according to geographic region, nodal status, centrally assessed hormonal receptor status and type of anthracycline.
Arm/Group Title Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
Hide Arm/Group Description Trastuzumab and pertuzumab were administered concurrently for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy. Trastuzumab emtansine and pertuzumab continued for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
Period Title: Overall Study
Started 918 928
Completed [1] 815 815
Not Completed 103 113
Reason Not Completed
Death             33             44
Lost to Follow-up             14             16
Other             3             5
Physician Decision             5             5
Withdrawal by Subject             48             43
[1]
The study is ongoing and these numbers represent the number of participants continuing in the study.
Arm/Group Title Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab Total
Hide Arm/Group Description Trastuzumab and pertuzumab were administered concurrently for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy. Trastuzumab emtansine and pertuzumab continued for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy. Total of all reporting groups
Overall Number of Baseline Participants 918 928 1846
Hide Baseline Analysis Population Description
Baseline Measures are based on the Intent-to-Treat (ITT) population.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 918 participants 928 participants 1846 participants
51.6  (10.8) 51.9  (10.8) 51.7  (10.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 918 participants 928 participants 1846 participants
Female
913
  99.5%
926
  99.8%
1839
  99.6%
Male
5
   0.5%
2
   0.2%
7
   0.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 918 participants 928 participants 1846 participants
Hispanic or Latino
70
   7.6%
68
   7.3%
138
   7.5%
Not Hispanic or Latino
798
  86.9%
790
  85.1%
1588
  86.0%
Unknown or Not Reported
50
   5.4%
70
   7.5%
120
   6.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 918 participants 928 participants 1846 participants
American Indian or Alaska Native
12
   1.3%
12
   1.3%
24
   1.3%
Asian
267
  29.1%
275
  29.6%
542
  29.4%
Native Hawaiian or Other Pacific Islander
1
   0.1%
1
   0.1%
2
   0.1%
Black or African American
15
   1.6%
8
   0.9%
23
   1.2%
White
558
  60.8%
565
  60.9%
1123
  60.8%
More than one race
2
   0.2%
2
   0.2%
4
   0.2%
Unknown or Not Reported
63
   6.9%
65
   7.0%
128
   6.9%
1.Primary Outcome
Title Invasive Disease-Free Survival (IDFS) in the Node-Positive Subpopulation
Hide Description IDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. 3-year IDFS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.
Time Frame First participant randomized to data cut-off date of 27 November 2019 (approximately 70 months). The 3 year IDFS event-free rate was assessed based on the data collected for each participant considering the cut-off date mentioned above.
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT lymph node positive population was a subpopulation of the randomized participant population including patients with positive lymph node.
Arm/Group Title Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
Hide Arm/Group Description:
Trastuzumab and pertuzumab were administered concurrently for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
Trastuzumab emtansine and pertuzumab continued for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
Overall Number of Participants Analyzed 826 832
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent Probability
94.10
(92.46 to 95.73)
92.75
(90.95 to 94.54)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane, Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8270
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval 95%
0.71 to 1.32
Estimation Comments [Not Specified]
2.Primary Outcome
Title Invasive Disease-Free Survival (IDFS) in the Overall Population
Hide Description IDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. 3-year IDFS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.
Time Frame First participant randomized to data cut-off date of 27 November 2019 (approximately 70 months). The 3 year IDFS event-free rate was assessed based on the data collected for each participant considering the cut-off date mentioned above.
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population comprised all randomized patients, whether or not they received any study treatment or completed a full course of study treatment. Patients were analyzed according to their randomized treatment.
Arm/Group Title Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
Hide Arm/Group Description:
Trastuzumab and pertuzumab were administered concurrently for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
Trastuzumab emtansine and pertuzumab continued for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
Overall Number of Participants Analyzed 918 928
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent Probability
94.22
(92.68 to 95.76)
93.05
(91.38 to 94.72)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane, Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8692
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.98
Confidence Interval 95%
0.72 to 1.32
Estimation Comments [Not Specified]
3.Secondary Outcome
Title IDFS Plus Second Primary Non-Breast Cancer
Hide Description IDFS including second primary non-breast cancer was defined the same way as IDFS for the primary endpoint but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and carcinoma in situ (CIS) of any site). 3-year IDFS including second primary non-breast cancer event-free rates per treatment arm in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.
Time Frame Baseline up to approximately 10 years
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Disease-Free Survival (DFS)
Hide Description DFS was defined as time between randomization and first occurrence of IDFS, second primary non-breast cancer and contralateral or ipsilateral ductal carcinoma in situ (DCIS). 3-year DFS event-free rates per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.
Time Frame Baseline up to approximately 10 years
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Distant Recurrence-Free Interval (DRFI)
Hide Description DRFI was defined as time between randomization and first occurrence of distant breast cancer recurrence. 3 years DRFI event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.
Time Frame Baseline up to approximately 10 years
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from randomization to death due to any cause. 5 years OS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 5 years after randomization.
Time Frame Baseline up to approximately 10 years
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Percentage of Participants With Adverse Events
Hide Description An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0).
Time Frame From randomization to data cut-off date of 27 November 2019 (approximately 70 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all randomized participants who received at least one full or partial dose of any study treatment. 8 participants were randomized but did not receive any study treatment (5 in the Anthracycline, Trastuzumab, Pertuzumab, and Taxane [AC-THP] arm, 3 in the Anthracycline, Trastuzumab Emtansine and Pertuzumab [AC-KP] arm). 16 participants in the AC-THP and 13 participants in the AC-KP arm only received AC but no HER2 targeted therapy and were assigned to the AC-THP arm.
Arm/Group Title Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
Hide Arm/Group Description:
Trastuzumab and pertuzumab were administered concurrently for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
Trastuzumab emtansine and pertuzumab continued for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
Overall Number of Participants Analyzed 926 912
Measure Type: Number
Unit of Measure: Percentage of participants
98.5 99.1
8.Secondary Outcome
Title Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) From Baseline Over Time
Hide Description LVEF was assessed using either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans.
Time Frame Baseline up to approximately 10 years
Outcome Measure Data Not Reported
9.Secondary Outcome
Title European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score
Hide Description The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 7 - 15 points considered to be a clinically meaningful detioration to participants. A positive value means an increase, while a negative value means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1).
Time Frame Baseline, Cycles 1, 2, 3, 4, 5, 9, 14, End of Treatment, Follow-up Month 6, Follow-up Month 12, Follow-up Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Patient Reported Outcome (PRO) Population includes participants with both a baseline assessment and at least one post-baseline assessment in any PRO items. The variation of the number of participants in the table reflects the number of participants with corresponding scores at the given visits and at baseline.
Arm/Group Title Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
Hide Arm/Group Description:
Trastuzumab and pertuzumab were administered concurrently for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
Trastuzumab emtansine and pertuzumab continued for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
Overall Number of Participants Analyzed 869 891
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Baseline: Appetite Loss Number Analyzed 869 participants 888 participants
8.2  (17.6) 7.6  (16.8)
Change at Cycle 1: Appetite Loss Number Analyzed 835 participants 857 participants
12.2  (27.9) 10.8  (26.6)
Change at Cycle 2: Appetite Loss Number Analyzed 816 participants 827 participants
15.2  (27.7) 13.1  (26.7)
Change at Cycle 3: Appetite Loss Number Analyzed 816 participants 833 participants
14.3  (28.2) 10.3  (25.7)
Change at Cycle 4: Appetite Loss Number Analyzed 815 participants 834 participants
16.2  (29.8) 9.4  (25.5)
Change at Cycle 5: Appetite Loss Number Analyzed 814 participants 826 participants
12.0  (28.4) 9.0  (26.2)
Change at Cycle 9: Appetite Loss Number Analyzed 792 participants 792 participants
5.7  (23.9) 8.2  (25.7)
Change at Cycle 14: Appetite Loss Number Analyzed 772 participants 750 participants
2.2  (23.1) 6.4  (25.4)
Change at EoT: Appetite Loss Number Analyzed 806 participants 810 participants
0.5  (22.3) 5.6  (25.1)
Change at FU Month 6: Appetite Loss Number Analyzed 766 participants 744 participants
-1.3  (20.7) -2.4  (20.3)
Change at FU Month 12: Appetite Loss Number Analyzed 738 participants 722 participants
-2.2  (20.8) -2.3  (20.5)
Change at FU Month 18: Appetite Loss Number Analyzed 0 participants 2 participants
-16.7  (23.6)
Baseline: Constipation Number Analyzed 869 participants 884 participants
9.6  (19.4) 9.0  (19.6)
Change at Cycle 1: Constipation Number Analyzed 835 participants 855 participants
8.4  (22.5) 8.0  (26.1)
Change at Cycle 2: Constipation Number Analyzed 812 participants 821 participants
1.1  (25.0) 0.9  (23.1)
Change at Cycle 3: Constipation Number Analyzed 812 participants 829 participants
2.0  (24.6) 0.2  (22.2)
Change at Cycle 4: Constipation Number Analyzed 811 participants 829 participants
2.5  (24.3) -0.6  (23.2)
Change at Cycle 5: Constipation Number Analyzed 813 participants 820 participants
0.5  (22.4) -0.4  (22.1)
Change at Cycle 9: Constipation Number Analyzed 792 participants 788 participants
-0.7  (21.7) 3.3  (24.7)
Change at Cycle 14: Constipation Number Analyzed 772 participants 743 participants
0.6  (21.1) 4.2  (24.6)
Change at EoT: Constipation Number Analyzed 805 participants 805 participants
0.2  (21.8) 4.7  (25.1)
Change at FU Month 6: Constipation Number Analyzed 766 participants 742 participants
3.4  (23.2) 1.5  (24.1)
Change at FU Month 12: Constipation Number Analyzed 740 participants 719 participants
2.8  (22.8) 2.0  (23.3)
Change at FU Month 18: Constipation Number Analyzed 0 participants 2 participants
0.0  (0.0)
Baseline: Diarrhea Number Analyzed 864 participants 878 participants
5.2  (13.2) 4.7  (12.9)
Change at Cycle 1: Diarrhea Number Analyzed 832 participants 848 participants
4.7  (20.3) 4.2  (18.4)
Change at Cycle 2: Diarrhea Number Analyzed 813 participants 815 participants
32.5  (32.8) 16.0  (26.9)
Change at Cycle 3: Diarrhea Number Analyzed 814 participants 824 participants
28.4  (30.5) 11.3  (23.5)
Change at Cycle 4: Diarrhea Number Analyzed 810 participants 824 participants
26.5  (30.0) 10.3  (23.6)
Change at Cycle 5: Diarrhea Number Analyzed 808 participants 815 participants
23.9  (30.4) 8.8  (22.8)
Change at Cycle 9: Diarrhea Number Analyzed 788 participants 786 participants
12.6  (24.6) 4.7  (21.7)
Change at Cycle 14: Diarrhea Number Analyzed 767 participants 740 participants
12.5  (26.4) 5.1  (20.3)
Change at EoT: Diarrhea Number Analyzed 805 participants 798 participants
10.3  (25.2) 3.0  (19.4)
Change at FU Month 6: Diarrhea Number Analyzed 759 participants 734 participants
-0.3  (16.4) -1.1  (16.3)
Change at FU Month 12: Diarrhea Number Analyzed 732 participants 712 participants
-0.3  (17.8) 0.0  (17.1)
Change at FU Month 18: Diarrhea Number Analyzed 0 participants 2 participants
-16.7  (23.6)
Baseline: Dyspnea Number Analyzed 869 participants 887 participants
5.8  (14.0) 6.2  (14.3)
Change at Cycle 1: Dyspnea Number Analyzed 838 participants 856 participants
10.4  (21.4) 9.2  (21.8)
Change at Cycle 2: Dyspnea Number Analyzed 816 participants 825 participants
11.6  (22.0) 7.4  (20.6)
Change at Cycle 3: Dyspnea Number Analyzed 817 participants 833 participants
13.4  (23.2) 6.5  (20.5)
Change at Cycle 4: Dyspnea Number Analyzed 816 participants 833 participants
14.3  (23.7) 5.9  (20.8)
Change at Cycle 5: Dyspnea Number Analyzed 816 participants 826 participants
13.7  (22.4) 5.6  (19.8)
Change at Cycle 9: Dyspnea Number Analyzed 790 participants 792 participants
7.8  (19.3) 7.5  (21.4)
Change at Cycle 14: Dyspnea Number Analyzed 773 participants 750 participants
6.8  (20.8) 8.1  (21.6)
Change at EoT: Dyspnea Number Analyzed 805 participants 809 participants
7.6  (21.1) 8.8  (22.3)
Change at FU Month 6: Dyspnea Number Analyzed 766 participants 743 participants
7.0  (20.8) 5.3  (19.7)
Change at FU Month 12: Dyspnea Number Analyzed 740 participants 722 participants
6.2  (20.9) 5.8  (20.5)
Change at FU Month 18: Dyspnea Number Analyzed 0 participants 2 participants
-16.7  (23.6)
Baseline: Fatigue Number Analyzed 868 participants 887 participants
21.5  (18.6) 20.6  (18.6)
Change at Cycle 1: Fatigue Number Analyzed 837 participants 857 participants
13.2  (21.5) 14.4  (22.1)
Change at Cycle 2: Fatigue Number Analyzed 815 participants 825 participants
15.4  (22.7) 11.2  (21.7)
Change at Cycle 3: Fatigue Number Analyzed 816 participants 833 participants
15.3  (23.1) 8.7  (20.9)
Change at Cycle 4: Fatigue Number Analyzed 816 participants 834 participants
16.0  (23.4) 8.2  (20.7)
Change at Cycle 5: Fatigue Number Analyzed 815 participants 826 participants
14.9  (22.8) 8.4  (21.1)
Change at Cycle 9: Fatigue Number Analyzed 790 participants 791 participants
8.4  (22.0) 9.8  (20.8)
Change at Cycle 14: Fatigue Number Analyzed 772 participants 751 participants
6.7  (22.0) 10.6  (22.4)
Change at EoT: Fatigue Number Analyzed 808 participants 809 participants
5.5  (22.9) 9.3  (21.9)
Change at FU Month 6: Fatigue Number Analyzed 765 participants 744 participants
2.8  (21.9) 3.1  (21.9)
Change at FU Month 12: Fatigue Number Analyzed 739 participants 722 participants
1.9  (22.1) 1.8  (20.8)
Change at FU Month 18: Fatigue Number Analyzed 0 participants 2 participants
-5.6  (39.3)
Baseline: Financial Difficulties Number Analyzed 859 participants 876 participants
20.1  (28.3) 19.9  (28.5)
Change at Cycle 1: Financial Difficulties Number Analyzed 825 participants 843 participants
2.2  (25.2) 0.3  (24.8)
Change at Cycle 2: Financial Difficulties Number Analyzed 808 participants 810 participants
2.0  (25.7) -0.6  (25.3)
Change at Cycle 3: Financial Difficulties Number Analyzed 810 participants 820 participants
3.9  (24.7) -0.4  (25.0)
Change at Cycle 4: Financial Difficulties Number Analyzed 802 participants 820 participants
3.7  (24.9) -0.2  (25.4)
Change at Cycle 5: Financial Difficulties Number Analyzed 801 participants 811 participants
3.4  (25.3) 0.7  (26.2)
Change at Cycle 9: Financial Difficulties Number Analyzed 784 participants 782 participants
0.9  (25.6) -0.5  (26.6)
Change at Cycle 14: Financial Difficulties Number Analyzed 763 participants 736 participants
-1.4  (25.1) -1.0  (27.2)
Change at EoT: Financial Difficulties Number Analyzed 799 participants 797 participants
-1.1  (27.3) -1.7  (25.7)
Change at FU Month 6: Financial Difficulties Number Analyzed 755 participants 732 participants
-3.8  (27.4) -5.2  (28.7)
Change at FU Month 12: Financial Difficulties Number Analyzed 728 participants 708 participants
-5.1  (28.6) -6.8  (28.3)
Change at FU Month 18: Financial Difficulties Number Analyzed 0 participants 2 participants
0.0  (0.0)
Baseline: Insomnia Number Analyzed 869 participants 888 participants
23.9  (26.1) 24.9  (27.6)
Change at Cycle 1: Insomnia Number Analyzed 838 participants 857 participants
3.6  (30.2) 1.8  (28.8)
Change at Cycle 2: Insomnia Number Analyzed 816 participants 828 participants
6.0  (30.5) 0.4  (30.0)
Change at Cycle 3: Insomnia Number Analyzed 815 participants 835 participants
6.2  (30.2) -0.1  (30.3)
Change at Cycle 4: Insomnia Number Analyzed 817 participants 835 participants
8.6  (31.3) 1.1  (30.4)
Change at Cycle 5: Insomnia Number Analyzed 814 participants 827 participants
5.2  (31.1) 1.1  (29.9)
Change at Cycle 9: Insomnia Number Analyzed 790 participants 791 participants
4.3  (30.5) 1.1  (29.9)
Change at Cycle 14: Insomnia Number Analyzed 773 participants 751 participants
2.7  (30.6) 2.7  (30.2)
Change at EoT: Insomnia Number Analyzed 807 participants 810 participants
2.5  (30.8) 0.9  (30.2)
Change at FU Month 6: Insomnia Number Analyzed 765 participants 744 participants
0.9  (29.5) -2.3  (29.6)
Change at FU Month 12: Insomnia Number Analyzed 739 participants 724 participants
0.0  (30.2) -2.9  (30.4)
Change at FU Month 18: Insomnia Number Analyzed 0 participants 2 participants
-16.7  (23.6)
Baseline: Nausea/Vomiting Number Analyzed 869 participants 887 participants
2.6  (9.4) 2.3  (7.1)
Change at Cycle 1: Nausea/Vomiting Number Analyzed 839 participants 856 participants
10.4  (19.5) 10.5  (17.8)
Change at Cycle 2: Nausea/Vomiting Number Analyzed 816 participants 827 participants
6.0  (16.5) 7.5  (16.1)
Change at Cycle 3: Nausea/Vomiting Number Analyzed 817 participants 833 participants
5.0  (16.2) 5.2  (13.9)
Change at Cycle 4: Nausea/Vomiting Number Analyzed 816 participants 834 participants
4.7  (16.0) 3.7  (12.8)
Change at Cycle 5: Nausea/Vomiting Number Analyzed 817 participants 826 participants
4.0  (15.6) 3.2  (13.1)
Change at Cycle 9: Nausea/Vomiting Number Analyzed 792 participants 792 participants
1.1  (13.8) 2.8  (11.5)
Change at Cycle 14: Nausea/Vomiting Number Analyzed 773 participants 751 participants
1.1  (12.3) 3.0  (12.1)
Change at EoT: Nausea/Vomiting Number Analyzed 806 participants 809 participants
0.9  (13.2) 1.7  (12.0)
Change at FU Month 6: Nausea/Vomiting Number Analyzed 766 participants 744 participants
0.2  (11.6) 0.1  (10.1)
Change at FU Month 12: Nausea/Vomiting Number Analyzed 740 participants 721 participants
0.5  (12.4) 0.6  (10.3)
Change at FU Month 18: Nausea/Vomiting Number Analyzed 0 participants 2 participants
-8.3  (11.8)
Baseline: Pain Number Analyzed 869 participants 889 participants
17.4  (20.1) 16.4  (20.0)
Change at Cycle 1: Pain Number Analyzed 839 participants 859 participants
1.8  (22.8) 1.1  (22.5)
Change at Cycle 2: Pain Number Analyzed 816 participants 828 participants
5.0  (24.5) 2.8  (23.1)
Change at Cycle 3: Pain Number Analyzed 818 participants 836 participants
3.5  (23.7) 2.5  (22.6)
Change at Cycle 4: Pain Number Analyzed 817 participants 836 participants
5.4  (23.2) 3.1  (23.5)
Change at Cycle 5: Pain Number Analyzed 817 participants 828 participants
5.2  (23.7) 3.8  (23.5)
Change at Cycle 9: Pain Number Analyzed 791 participants 792 participants
3.4  (22.6) 3.9  (23.3)
Change at Cycle 14: Pain Number Analyzed 773 participants 753 participants
2.0  (23.4) 5.7  (24.1)
Change at EoT: Pain Number Analyzed 809 participants 812 participants
1.9  (23.3) 5.1  (24.5)
Change at FU Month 6: Pain Number Analyzed 766 participants 746 participants
0.8  (23.0) 1.4  (22.6)
Change at FU Month 12: Pain Number Analyzed 741 participants 725 participants
0.0  (23.3) 0.5  (21.5)
Change at FU Month 18: Pain Number Analyzed 0 participants 2 participants
-25.0  (35.4)
Baseline: Cognitive Functioning Number Analyzed 864 participants 879 participants
88.6  (16.9) 88.7  (16.3)
Change at Cycle 1: Cognitive Functioning Number Analyzed 832 participants 851 participants
-9.7  (20.8) -6.9  (19.3)
Change at Cycle 2: Cognitive Functioning Number Analyzed 813 participants 818 participants
-9.4  (20.0) -6.8  (19.3)
Change at Cycle 3: Cognitive Functioning Number Analyzed 814 participants 824 participants
-10.1  (20.8) -6.4  (19.4)
Change at Cycle 4: Cognitive Functioning Number Analyzed 810 participants 825 participants
-11.8  (21.6) -6.9  (19.6)
Change at Cycle 5: Cognitive Functioning Number Analyzed 807 participants 816 participants
-10.8  (21.6) -7.3  (20.3)
Change at Cycle 9: Cognitive Functioning Number Analyzed 789 participants 787 participants
-8.3  (20.2) -7.6  (20.1)
Change at Cycle 14: Cognitive Functioning Number Analyzed 768 participants 742 participants
-8.1  (20.3) -8.1  (20.6)
Change at EoT: Cognitive Functioning Number Analyzed 805 participants 800 participants
-8.7  (22.3) -8.4  (20.9)
Change at FU Month 6: Cognitive Functioning Number Analyzed 760 participants 735 participants
-8.0  (20.4) -6.1  (19.7)
Change at FU Month 12: Cognitive Functioning Number Analyzed 733 participants 713 participants
-7.1  (22.5) -6.0  (20.7)
Change at FU Month 18: Cognitive Functioning Number Analyzed 0 participants 2 participants
16.7  (23.6)
Baseline: Emotional Functioning Number Analyzed 864 participants 880 participants
76.0  (19.7) 75.7  (20.9)
Change at Cycle 1: Emotional Functioning Number Analyzed 832 participants 849 participants
-1.1  (20.3) 0.0  (19.2)
Change at Cycle 2: Emotional Functioning Number Analyzed 813 participants 819 participants
-1.0  (20.8) 1.6  (19.7)
Change at Cycle 3: Emotional Functioning Number Analyzed 814 participants 825 participants
-0.9  (21.2) 2.2  (19.6)
Change at Cycle 4: Emotional Functioning Number Analyzed 810 participants 826 participants
-2.5  (22.3) 2.8  (20.0)
Change at Cycle 5: Emotional Functioning Number Analyzed 808 participants 817 participants
-1.2  (22.2) 2.6  (21.1)
Change at Cycle 9: Emotional Functioning Number Analyzed 789 participants 788 participants
3.1  (20.9) 2.9  (21.1)
Change at Cycle 14: Emotional Functioning Number Analyzed 768 participants 743 participants
4.1  (21.0) 2.5  (21.3)
Change at EoT: Emotional Functioning Number Analyzed 806 participants 801 participants
3.0  (22.4) 3.1  (21.3)
Change at FU Month 6: Emotional Functioning Number Analyzed 760 participants 736 participants
4.7  (21.2) 6.1  (21.8)
Change at FU Month 12: Emotional Functioning Number Analyzed 733 participants 714 participants
5.8  (22.1) 6.5  (21.9)
Change at FU Month 18: Emotional Functioning Number Analyzed 0 participants 2 participants
12.5  (17.7)
Baseline: Physical Functioning Number Analyzed 869 participants 889 participants
88.4  (13.5) 89.1  (12.3)
Change at Cycle 1: Physical Functioning Number Analyzed 838 participants 859 participants
-6.0  (14.5) -5.9  (13.4)
Change at Cycle 2: Physical Functioning Number Analyzed 816 participants 827 participants
-7.8  (15.8) -4.8  (12.8)
Change at Cycle 3: Physical Functioning Number Analyzed 817 participants 835 participants
-7.1  (15.4) -4.1  (13.0)
Change at Cycle 4: Physical Functioning Number Analyzed 816 participants 835 participants
-8.4  (16.2) -3.5  (13.1)
Change at Cycle 5: Physical Functioning Number Analyzed 817 participants 827 participants
-8.3  (16.1) -3.5  (13.3)
Change at Cycle 9: Physical Functioning Number Analyzed 789 participants 793 participants
-4.0  (15.0) -3.8  (14.2)
Change at Cycle 14: Physical Functioning Number Analyzed 773 participants 752 participants
-2.7  (14.2) -4.2  (14.2)
Change at EoT: Physical Functioning Number Analyzed 805 participants 810 participants
-2.2  (14.7) -4.9  (15.0)
Change at FU Month 6: Physical Functioning Number Analyzed 766 participants 747 participants
-0.6  (14.4) -1.6  (13.6)
Change at FU Month 12: Physical Functioning Number Analyzed 739 participants 724 participants
-0.1  (15.4) -0.8  (13.2)
Change at FU Month 18: Physical Functioning Number Analyzed 0 participants 2 participants
13.3  (18.9)
Baseline: Role Functioning Number Analyzed 869 participants 889 participants
83.1  (21.7) 83.4  (21.3)
Change at Cycle 1: Role Functioning Number Analyzed 837 participants 859 participants
-5.1  (24.5) -5.7  (24.9)
Change at Cycle 2: Role Functioning Number Analyzed 816 participants 828 participants
-9.7  (26.6) -5.5  (24.0)
Change at Cycle 3: Role Functioning Number Analyzed 817 participants 835 participants
-8.9  (26.7) -2.7  (23.2)
Change at Cycle 4: Role Functioning Number Analyzed 815 participants 836 participants
-10.7  (27.5) -3.2  (23.7)
Change at Cycle 5: Role Functioning Number Analyzed 817 participants 827 participants
-9.4  (27.3) -3.5  (23.9)
Change at Cycle 9: Role Functioning Number Analyzed 792 participants 792 participants
-3.3  (25.4) -3.2  (24.1)
Change at Cycle 14: Role Functioning Number Analyzed 772 participants 752 participants
-0.5  (25.0) -4.3  (25.3)
Change at EoT: Role Functioning Number Analyzed 806 participants 811 participants
-0.2  (26.3) -3.5  (24.9)
Change at FU Month 6: Role Functioning Number Analyzed 766 participants 746 participants
2.2  (24.7) 2.4  (24.1)
Change at FU Month 12: Role Functioning Number Analyzed 740 participants 724 participants
2.6  (25.9) 3.7  (23.8)
Change at FU Month 18: Role Functioning Number Analyzed 0 participants 2 participants
8.3  (11.8)
Baseline: Social Functioning Number Analyzed 863 participants 877 participants
83.0  (22.9) 83.2  (21.6)
Change at Cycle 1: Social Functioning Number Analyzed 831 participants 849 participants
-8.0  (24.3) -5.3  (22.8)
Change at Cycle 2: Social Functioning Number Analyzed 812 participants 816 participants
-10.1  (26.1) -4.1  (23.6)
Change at Cycle 3: Social Functioning Number Analyzed 814 participants 823 participants
-9.5  (25.6) -3.3  (24.4)
Change at Cycle 4: Social Functioning Number Analyzed 808 participants 823 participants
-10.3  (26.3) -3.2  (24.2)
Change at Cycle 5: Social Functioning Number Analyzed 808 participants 815 participants
-8.7  (26.5) -2.6  (23.7)
Change at Cycle 9: Social Functioning Number Analyzed 789 participants 785 participants
-1.7  (25.1) -3.4  (24.9)
Change at Cycle 14: Social Functioning Number Analyzed 768 participants 738 participants
-0.1  (25.3) -2.4  (24.9)
Change at EoT: Social Functioning Number Analyzed 804 participants 798 participants
0.3  (26.1) -1.6  (24.1)
Change at FU Month 6: Social Functioning Number Analyzed 759 participants 733 participants
3.3  (24.8) 4.0  (24.7)
Change at FU Month 12: Social Functioning Number Analyzed 732 participants 711 participants
4.6  (25.2) 6.4  (22.7)
Change at FU Month 18: Social Functioning Number Analyzed 0 participants 2 participants
33.3  (47.1)
Baseline: Global Health Status Number Analyzed 863 participants 878 participants
74.3  (18.7) 73.9  (18.7)
Change at Cycle 1: Global Health Status Number Analyzed 831 participants 850 participants
-7.5  (20.1) -7.2  (20.4)
Change at Cycle 2: Global Health Status Number Analyzed 812 participants 815 participants
-12.4  (22.6) -7.1  (20.2)
Change at Cycle 3: Global Health Status Number Analyzed 814 participants 823 participants
-11.7  (20.6) -5.2  (19.1)
Change at Cycle 4: Global Health Status Number Analyzed 807 participants 824 participants
-12.7  (21.3) -5.5  (19.6)
Change at Cycle 5: Global Health Status Number Analyzed 807 participants 815 participants
-12.1  (21.7) -5.8  (19.7)
Change at Cycle 9: Global Health Status Number Analyzed 784 participants 787 participants
-5.9  (20.1) -6.4  (20.6)
Change at Cycle 14: Global Health Status Number Analyzed 766 participants 741 participants
-3.9  (21.1) -6.3  (20.8)
Change at EoT: Global Health Status Number Analyzed 804 participants 798 participants
-3.5  (21.3) -4.9  (20.7)
Change at FU Month 6: Global Health Status Number Analyzed 758 participants 733 participants
-0.6  (21.3) 0.3  (21.4)
Change at FU Month 12: Global Health Status Number Analyzed 731 participants 712 participants
-0.2  (21.9) 1.2  (20.8)
Change at FU Month 18: Global Health Status Number Analyzed 0 participants 2 participants
16.7  (23.6)
10.Secondary Outcome
Title EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score
Hide Description EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30. There are four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Higher scores for symptom scales represent higher levels of symptoms/problems. For functional scales, positive change from baseline indicated improvement in quality of life (QOL) while negative change from baseline indicated a deterioration. For symptom scales, positive change from baseline indicated deterioration and negative change indicated improvement.
Time Frame Baseline, Cycles 1, 2, 3, 4, 5, 9, 14, End of Treatment, Follow-up Month 6, Follow-up Month 12, Follow-up Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Patient Reported Outcome (PRO) Population includes participants with both a baseline assessment and at least one post-baseline assessment in any PRO items. The variation of the number of participants in the table reflects the number of participants with corresponding scores at the given visits and at baseline.
Arm/Group Title Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
Hide Arm/Group Description:
Trastuzumab and pertuzumab were administered concurrently for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
Trastuzumab emtansine and pertuzumab continued for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
Overall Number of Participants Analyzed 869 891
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Baseline: Arm Symptoms Number Analyzed 844 participants 861 participants
19.9  (18.7) 19.5  (18.4)
Change at Cycle 1: Arm Symptoms Number Analyzed 804 participants 831 participants
-1.3  (19.2) -3.1  (18.7)
Change at Cycle 2: Arm Symptoms Number Analyzed 788 participants 798 participants
-2.8  (18.8) -3.0  (18.7)
Change at Cycle 3: Arm Symptoms Number Analyzed 788 participants 805 participants
-3.5  (18.7) -3.5  (18.1)
Change at Cycle 4: Arm Symptoms Number Analyzed 786 participants 803 participants
-2.0  (19.8) -2.9  (19.2)
Change at Cycle 5: Arm Symptoms Number Analyzed 790 participants 798 participants
-0.5  (20.8) -2.6  (19.8)
Change at Cycle 9: Arm Symptoms Number Analyzed 768 participants 765 participants
-0.2  (20.4) -1.1  (19.6)
Change at Cycle 14: Arm Symptoms Number Analyzed 754 participants 725 participants
0.3  (21.3) 1.3  (21.8)
Change at EoT: Arm Symptoms Number Analyzed 784 participants 785 participants
0.1  (21.6) 0.4  (21.7)
Change at FU Month 6: Arm Symptoms Number Analyzed 739 participants 716 participants
-0.1  (22.1) -1.3  (20.0)
Change at FU Month 12: Arm Symptoms Number Analyzed 714 participants 693 participants
-0.8  (22.4) -2.8  (20.5)
Change at FU Month 18: Arm Symptoms Number Analyzed 0 participants 0 participants
Baseline: Breast Symptoms Number Analyzed 843 participants 859 participants
17.5  (17.4) 16.8  (16.3)
Change at Cycle 1: Breast Symptoms Number Analyzed 802 participants 828 participants
-2.3  (16.3) -2.5  (16.2)
Change at Cycle 2: Breast Symptoms Number Analyzed 786 participants 795 participants
-3.3  (17.1) -2.9  (16.7)
Change at Cycle 3: Breast Symptoms Number Analyzed 785 participants 803 participants
-4.0  (17.5) -3.1  (16.5)
Change at Cycle 4: Breast Symptoms Number Analyzed 786 participants 800 participants
-3.9  (17.7) -3.3  (17.4)
Change at Cycle 5: Breast Symptoms Number Analyzed 787 participants 796 participants
-3.1  (18.6) -2.6  (18.2)
Change at Cycle 9: Breast Symptoms Number Analyzed 768 participants 763 participants
1.7  (19.7) 0.3  (17.5)
Change at Cycle 14: Breast Symptoms Number Analyzed 751 participants 724 participants
-0.2  (18.8) 0.5  (19.1)
Change at EoT: Breast Symptoms Number Analyzed 781 participants 783 participants
-1.0  (19.3) 0.3  (18.8)
Change at FU Month 6: Breast Symptoms Number Analyzed 738 participants 714 participants
-2.5  (19.1) -1.5  (18.4)
Change at FU Month 12: Breast Symptoms Number Analyzed 713 participants 691 participants
-4.2  (18.9) -3.7  (18.0)
Change at FU Month 18: Breast Symptoms Number Analyzed 0 participants 0 participants
Baseline: Systemic Therapy Side Effects (SE) Number Analyzed 845 participants 868 participants
8.5  (9.9) 8.7  (9.9)
Change at Cycle 1: Systemic Therapy SE Number Analyzed 812 participants 838 participants
24.9  (17.3) 23.3  (17.6)
Change at Cycle 2: Systemic Therapy SE Number Analyzed 791 participants 805 participants
24.1  (18.1) 18.3  (16.6)
Change at Cycle 3: Systemic Therapy SE Number Analyzed 793 participants 812 participants
23.4  (17.8) 15.1  (15.5)
Change at Cycle 4: Systemic Therapy SE Number Analyzed 793 participants 814 participants
23.1  (18.1) 13.2  (15.4)
Change at Cycle 5: Systemic Therapy SE Number Analyzed 793 participants 806 participants
20.0  (17.6) 11.8  (14.7)
Change at Cycle 9: Systemic Therapy SE Number Analyzed 772 participants 770 participants
9.5  (13.1) 10.4  (14.0)
Change at Cycle 14: Systemic Therapy SE Number Analyzed 755 participants 730 participants
7.5  (12.9) 9.8  (13.9)
Change at EoT: Systemic Therapy SE Number Analyzed 785 participants 793 participants
7.2  (13.4) 8.5  (13.9)
Change at FU Month 6: Systemic Therapy SE Number Analyzed 745 participants 726 participants
5.8  (12.3) 4.2  (12.5)
Change at FU Month 12: Systemic Therapy SE Number Analyzed 716 participants 705 participants
5.4  (12.9) 4.2  (13.0)
Change at FU Month 18: Systemic Therapy SE Number Analyzed 0 participants 0 participants
Baseline: Upset by Hair Loss Item Number Analyzed 205 participants 213 participants
13.2  (23.7) 14.2  (22.9)
Change at Cycle 1: Upset by Hair Loss Item Number Analyzed 169 participants 168 participants
35.1  (37.3) 25.2  (35.1)
Change at Cycle 2: Upset by Hair Loss Item Number Analyzed 152 participants 130 participants
28.7  (36.0) 21.8  (36.6)
Change at Cycle 3: Upset by Hair Loss Item Number Analyzed 132 participants 98 participants
28.8  (36.3) 21.4  (38.4)
Change at Cycle 4: Upset by Hair Loss Item Number Analyzed 136 participants 83 participants
28.4  (37.1) 19.7  (34.2)
Change at Cycle 5: Upset by Hair Loss Item Number Analyzed 130 participants 83 participants
26.4  (36.8) 10.0  (36.3)
Change at Cycle 9: Upset by Hair Loss Item Number Analyzed 85 participants 72 participants
11.8  (33.6) 6.0  (36.8)
Change at Cycle 14: Upset by Hair Loss Item Number Analyzed 68 participants 53 participants
9.3  (32.5) 2.5  (26.0)
Change at EoT: Upset by Hair Loss Item Number Analyzed 75 participants 63 participants
17.3  (33.9) 0.0  (28.1)
Change at FU Month 6: Upset by Hair Loss Item Number Analyzed 86 participants 67 participants
6.2  (26.8) -3.5  (21.0)
Change at FU Month 12: Upset by Hair Loss Item Number Analyzed 84 participants 71 participants
2.4  (28.7) -2.8  (29.7)
Change at FU Month 18: Upset by Hair Loss Item Number Analyzed 0 participants 0 participants
Baseline: Body Image Number Analyzed 841 participants 867 participants
78.5  (23.2) 78.9  (24.2)
Change at Cycle 1: Body Image Number Analyzed 808 participants 834 participants
-13.7  (23.5) -13.3  (23.1)
Change at Cycle 2: Body Image Number Analyzed 788 participants 801 participants
-12.7  (23.9) -10.1  (23.9)
Change at Cycle 3: Body Image Number Analyzed 787 participants 807 participants
-11.5  (24.8) -6.6  (22.6)
Change at Cycle 4: Body Image Number Analyzed 788 participants 810 participants
-11.4  (24.8) -5.9  (23.2)
Change at Cycle 5: Body Image Number Analyzed 790 participants 802 participants
-10.5  (24.6) -5.0  (22.6)
Change at Cycle 9: Body Image Number Analyzed 768 participants 766 participants
-5.9  (22.8) -4.2  (21.7)
Change at Cycle 14: Body Image Number Analyzed 750 participants 726 participants
-4.5  (23.6) -2.4  (23.2)
Change at EoT: Body Image Number Analyzed 783 participants 785 participants
-3.3  (23.1) -2.9  (22.8)
Change at FU Month 6: Body Image Number Analyzed 740 participants 720 participants
-1.3  (23.4) 0.3  (23.3)
Change at FU Month 12: Body Image Number Analyzed 712 participants 703 participants
0.0  (24.2) 0.7  (23.5)
Change at FU Month 18: Body Image Number Analyzed 0 participants 0 participants
Baseline: Future Perspectives (FP) Number Analyzed 842 participants 868 participants
49.3  (31.4) 49.8  (30.9)
Change at Cycle 1: FP Number Analyzed 805 participants 836 participants
-1.3  (30.3) -0.3  (31.1)
Change at Cycle 2: FP Number Analyzed 786 participants 803 participants
1.4  (31.7) 3.7  (30.4)
Change at Cycle 3: FP Number Analyzed 786 participants 811 participants
3.2  (32.0) 6.5  (30.1)
Change at Cycle 4: FP Number Analyzed 787 participants 814 participants
4.2  (31.7) 7.8  (30.5)
Change at Cycle 5: FP Number Analyzed 787 participants 804 participants
5.9  (32.4) 9.7  (30.7)
Change at Cycle 9: FP Number Analyzed 762 participants 767 participants
8.2  (32.2) 8.4  (31.3)
Change at Cycle 14: FP Number Analyzed 752 participants 726 participants
9.5  (32.0) 7.9  (33.4)
Change at EoT: FP Number Analyzed 782 participants 787 participants
8.5  (32.6) 7.6  (32.3)
Change at FU Month 6: FP Number Analyzed 740 participants 720 participants
10.5  (31.3) 12.6  (32.6)
Change at FU Month 12: FP Number Analyzed 711 participants 703 participants
15.0  (34.0) 13.1  (33.2)
Change at FU Month 18: FP Number Analyzed 0 participants 0 participants
Baseline: Sexual Enjoyment Number Analyzed 369 participants 380 participants
43.4  (32.1) 46.7  (34.8)
Change at Cycle 1: Sexual Enjoyment Number Analyzed 233 participants 260 participants
-5.9  (26.8) -8.2  (27.0)
Change at Cycle 2: Sexual Enjoyment Number Analyzed 196 participants 227 participants
-9.5  (30.2) -10.7  (29.2)
Change at Cycle 3: Sexual Enjoyment Number Analyzed 205 participants 235 participants
-11.4  (26.8) -8.9  (31.6)
Change at Cycle 4: Sexual Enjoyment Number Analyzed 190 participants 228 participants
-11.9  (30.6) -9.2  (28.3)
Change at Cycle 5: Sexual Enjoyment Number Analyzed 204 participants 224 participants
-14.2  (28.1) -8.8  (30.4)
Change at Cycle 9: Sexual Enjoyment Number Analyzed 221 participants 220 participants
-9.4  (29.5) -7.4  (30.9)
Change at Cycle 14: Sexual Enjoyment Number Analyzed 203 participants 213 participants
-3.9  (28.6) -9.7  (31.4)
Change at EoT: Sexual Enjoyment Number Analyzed 224 participants 236 participants
-6.5  (29.2) -9.7  (29.4)
Change at FU Month 6: Sexual Enjoyment Number Analyzed 212 participants 223 participants
-4.6  (28.8) -3.0  (30.5)
Change at FU Month 12: Sexual Enjoyment Number Analyzed 212 participants 204 participants
-5.7  (30.9) -2.3  (31.0)
Change at FU Month 18: Sexual Enjoyment Number Analyzed 0 participants 0 participants
Baseline: Sexual Function Number Analyzed 819 participants 829 participants
16.7  (22.3) 18.3  (22.9)
Change at Cycle 1: Sexual Function Number Analyzed 757 participants 779 participants
-2.3  (18.9) -3.5  (18.4)
Change at Cycle 2: Sexual Function Number Analyzed 728 participants 745 participants
-4.8  (19.9) -4.4  (18.4)
Change at Cycle 3: Sexual Function Number Analyzed 734 participants 740 participants
-5.6  (19.6) -3.3  (19.0)
Change at Cycle 4: Sexual Function Number Analyzed 726 participants 743 participants
-6.8  (19.7) -3.4  (17.9)
Change at Cycle 5: Sexual Function Number Analyzed 730 participants 738 participants
-5.9  (19.5) -3.0  (19.5)
Change at Cycle 9: Sexual Function Number Analyzed 710 participants 704 participants
-3.4  (19.3) -1.8  (20.8)
Change at Cycle 14: Sexual Function Number Analyzed 696 participants 671 participants
-1.8  (20.0) -2.8  (20.6)
Change at EoT: Sexual Function Number Analyzed 716 participants 724 participants
-1.5  (20.9) -1.7  (19.7)
Change at FU Month 6: Sexual Function Number Analyzed 675 participants 658 participants
1.6  (22.6) 0.6  (20.4)
Change at FU Month 12: Sexual Function Number Analyzed 651 participants 639 participants
0.9  (21.7) 0.9  (20.9)
Change at FU Month 18: Sexual Function Number Analyzed 0 participants 0 participants
11.Secondary Outcome
Title Time to Clinically Meaningful Deterioration in the Global Health Status/ Quality of Life and Functional (Physical, Role, and Cognitive) Subscales of the QLQ-C30 From First HER2-Targeted Treatment
Hide Description The time to clinically meaningful deterioration in the global health status/HRQoL subscale (question 29 and 30 of the QLQ-C30) was used to assess the time from first HER2-targeted treatment to worsening in HRQoL. Clinically meaningful deterioration is defined as a decrease in score of 10 points in Physical functioning and HRQoL; decrease of 7 points in Cognitive functioning, and decrease of 14 points in Role functioning.
Time Frame From start of HER-2 targeted treatment up to 18 months after treatment discontinuation. The median time to clinically meaningful deterioration was assessed based on the data collection described above.
Hide Outcome Measure Data
Hide Analysis Population Description
The Patient Reported Outcome (PRO) Population includes participants with both a baseline assessment and at least one post-baseline assessment in any PRO items. This subset population includes only participants who received HER2-targeted therapy.
Arm/Group Title Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
Hide Arm/Group Description:
Trastuzumab and pertuzumab were administered concurrently for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
Trastuzumab emtansine and pertuzumab continued for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
Overall Number of Participants Analyzed 864 884
Median (95% Confidence Interval)
Unit of Measure: months
GHS/QoL Score Number Analyzed 858 participants 879 participants
2.73
(2.10 to 2.83)
13.57
(9.20 to 21.91)
Physical Function Number Analyzed 861 participants 879 participants
25.53 [1] 
(13.34 to NA)
NA [2] 
(27.43 to NA)
Role Function Number Analyzed 859 participants 880 participants
2.23
(2.10 to 2.79)
9.92
(9.00 to 14.36)
Cognitive Function Number Analyzed 858 participants 879 participants
5.49
(2.79 to 5.82)
9.46
(8.57 to 12.91)
[1]
Upper limit not reached.
[2]
The median and upper limit were not reached.
Time Frame From randomization to data cut-off date of 27 November 2019 (approximately 70 months)
Adverse Event Reporting Description AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0. 8 participants were randomized but did not receive any study treatment (5 in the AC-THP arm, 3 in the AC-KP arm). 16 participants in the AC-THP, and 13 in the AC-KP arm only received AC but no HER2 targeted therapy and were consequently assigned to the AC-THP arm for safety analysis.
 
Arm/Group Title Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
Hide Arm/Group Description Trastuzumab and pertuzumab were administered concurrently for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy. Trastuzumab emtansine and pertuzumab continued for up to a total duration of 1 year (up to 18 cycles [1 Cycle = 21 days]) following anthracycline [5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)] based chemotherapy.
All-Cause Mortality
Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
Affected / at Risk (%) Affected / at Risk (%)
Total   34/926 (3.67%)      44/912 (4.82%)    
Hide Serious Adverse Events
Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   216/926 (23.33%)      195/912 (21.38%)    
Blood and lymphatic system disorders     
ANAEMIA  1  2/926 (0.22%)  2 3/912 (0.33%)  3
FEBRILE NEUTROPENIA  1  51/926 (5.51%)  55 31/912 (3.40%)  32
LEUKOPENIA  1  2/926 (0.22%)  2 0/912 (0.00%)  0
NEUTROPENIA  1  16/926 (1.73%)  18 10/912 (1.10%)  11
THROMBOCYTOPENIA  1  0/926 (0.00%)  0 1/912 (0.11%)  1
Cardiac disorders     
ARRHYTHMIA  1  1/926 (0.11%)  1 0/912 (0.00%)  0
CARDIAC FAILURE  1  5/926 (0.54%)  5 2/912 (0.22%)  2
CARDIAC FAILURE CONGESTIVE  1  3/926 (0.32%)  3 1/912 (0.11%)  1
CARDIOMYOPATHY  1  0/926 (0.00%)  0 1/912 (0.11%)  1
CONGESTIVE CARDIOMYOPATHY  1  2/926 (0.22%)  2 0/912 (0.00%)  0
LEFT VENTRICULAR DYSFUNCTION  1  3/926 (0.32%)  3 1/912 (0.11%)  1
MYOCARDIAL INFARCTION  1  0/926 (0.00%)  0 1/912 (0.11%)  1
MYOCARDIAL ISCHAEMIA  1  0/926 (0.00%)  0 1/912 (0.11%)  1
SINUS TACHYCARDIA  1  1/926 (0.11%)  1 0/912 (0.00%)  0
Ear and labyrinth disorders     
HYPOACUSIS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
Eye disorders     
CATARACT  1  0/926 (0.00%)  0 1/912 (0.11%)  1
Gastrointestinal disorders     
ABDOMINAL PAIN  1  4/926 (0.43%)  4 4/912 (0.44%)  4
COLITIS  1  1/926 (0.11%)  1 1/912 (0.11%)  1
CONSTIPATION  1  1/926 (0.11%)  1 1/912 (0.11%)  1
DIARRHOEA  1  20/926 (2.16%)  22 8/912 (0.88%)  8
DIVERTICULUM  1  1/926 (0.11%)  1 0/912 (0.00%)  0
DUODENAL PERFORATION  1  1/926 (0.11%)  1 0/912 (0.00%)  0
DUODENAL ULCER  1  1/926 (0.11%)  1 0/912 (0.00%)  0
DUODENAL ULCER HAEMORRHAGE  1  0/926 (0.00%)  0 1/912 (0.11%)  2
DYSPHAGIA  1  0/926 (0.00%)  0 1/912 (0.11%)  1
ENTERITIS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
ENTEROCOLITIS  1  2/926 (0.22%)  2 0/912 (0.00%)  0
GASTRIC HAEMORRHAGE  1  0/926 (0.00%)  0 1/912 (0.11%)  1
GASTRIC ULCER HAEMORRHAGE  1  0/926 (0.00%)  0 1/912 (0.11%)  1
GASTRITIS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
GINGIVAL BLEEDING  1  0/926 (0.00%)  0 1/912 (0.11%)  1
HAEMATEMESIS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
HAEMORRHOIDS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
INTESTINAL OBSTRUCTION  1  0/926 (0.00%)  0 1/912 (0.11%)  1
MOUTH HAEMORRHAGE  1  0/926 (0.00%)  0 1/912 (0.11%)  1
NAUSEA  1  6/926 (0.65%)  6 9/912 (0.99%)  9
OESOPHAGITIS  1  2/926 (0.22%)  2 0/912 (0.00%)  0
PANCREATITIS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
PANCREATITIS ACUTE  1  0/926 (0.00%)  0 1/912 (0.11%)  1
PEPTIC ULCER HAEMORRHAGE  1  0/926 (0.00%)  0 1/912 (0.11%)  1
SMALL INTESTINAL HAEMORRHAGE  1  0/926 (0.00%)  0 1/912 (0.11%)  1
SMALL INTESTINAL OBSTRUCTION  1  0/926 (0.00%)  0 1/912 (0.11%)  1
STOMATITIS  1  2/926 (0.22%)  2 0/912 (0.00%)  0
UPPER GASTROINTESTINAL HAEMORRHAGE  1  0/926 (0.00%)  0 1/912 (0.11%)  1
VARICES OESOPHAGEAL  1  0/926 (0.00%)  0 1/912 (0.11%)  1
VOMITING  1  10/926 (1.08%)  10 7/912 (0.77%)  7
General disorders     
CATHETER SITE PAIN  1  0/926 (0.00%)  0 1/912 (0.11%)  3
CATHETER SITE VESICLES  1  0/926 (0.00%)  0 1/912 (0.11%)  1
CHEST DISCOMFORT  1  0/926 (0.00%)  0 1/912 (0.11%)  1
CHEST PAIN  1  1/926 (0.11%)  1 3/912 (0.33%)  3
FATIGUE  1  1/926 (0.11%)  1 1/912 (0.11%)  1
GENERAL PHYSICAL HEALTH DETERIORATION  1  1/926 (0.11%)  1 0/912 (0.00%)  0
IMPAIRED HEALING  1  1/926 (0.11%)  1 0/912 (0.00%)  0
INFLUENZA LIKE ILLNESS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
INFUSION SITE EXTRAVASATION  1  1/926 (0.11%)  1 0/912 (0.00%)  0
MALAISE  1  1/926 (0.11%)  1 0/912 (0.00%)  0
MEDICAL DEVICE PAIN  1  1/926 (0.11%)  1 0/912 (0.00%)  0
PYREXIA  1  13/926 (1.40%)  14 19/912 (2.08%)  22
Hepatobiliary disorders     
BILE DUCT OBSTRUCTION  1  0/926 (0.00%)  0 1/912 (0.11%)  1
CHOLECYSTITIS  1  1/926 (0.11%)  1 2/912 (0.22%)  2
CHOLELITHIASIS  1  1/926 (0.11%)  1 1/912 (0.11%)  2
NODULAR REGENERATIVE HYPERPLASIA  1  0/926 (0.00%)  0 3/912 (0.33%)  3
PORTAL HYPERTENSION  1  0/926 (0.00%)  0 1/912 (0.11%)  1
Immune system disorders     
ANAPHYLACTIC REACTION  1  0/926 (0.00%)  0 2/912 (0.22%)  2
DRUG HYPERSENSITIVITY  1  0/926 (0.00%)  0 2/912 (0.22%)  2
HYPERSENSITIVITY  1  1/926 (0.11%)  1 1/912 (0.11%)  1
Infections and infestations     
ANAL ABSCESS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
APPENDICITIS  1  2/926 (0.22%)  2 1/912 (0.11%)  1
ARTHRITIS BACTERIAL  1  0/926 (0.00%)  0 1/912 (0.11%)  1
ARTHRITIS INFECTIVE  1  0/926 (0.00%)  0 1/912 (0.11%)  1
BREAST CELLULITIS  1  1/926 (0.11%)  1 2/912 (0.22%)  2
BRONCHITIS  1  2/926 (0.22%)  2 2/912 (0.22%)  2
CATHETER SITE INFECTION  1  0/926 (0.00%)  0 1/912 (0.11%)  1
CELLULITIS  1  3/926 (0.32%)  3 4/912 (0.44%)  4
CHEST WALL ABSCESS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
CLOSTRIDIUM DIFFICILE INFECTION  1  1/926 (0.11%)  1 0/912 (0.00%)  0
DEVICE RELATED INFECTION  1  1/926 (0.11%)  1 3/912 (0.33%)  3
DEVICE RELATED SEPSIS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
DIVERTICULITIS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
ENTERITIS INFECTIOUS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
ENTEROCOLITIS INFECTIOUS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
ERYSIPELAS  1  1/926 (0.11%)  1 1/912 (0.11%)  1
GASTROENTERITIS  1  2/926 (0.22%)  2 2/912 (0.22%)  2
GASTROENTERITIS VIRAL  1  1/926 (0.11%)  1 2/912 (0.22%)  3
GASTROINTESTINAL BACTERIAL INFECTION  1  0/926 (0.00%)  0 1/912 (0.11%)  1
GENITAL HERPES  1  1/926 (0.11%)  1 1/912 (0.11%)  1
HERPES ZOSTER  1  2/926 (0.22%)  2 0/912 (0.00%)  0
INCISION SITE ABSCESS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
INFECTED SEROMA  1  1/926 (0.11%)  1 1/912 (0.11%)  1
INFLUENZA  1  4/926 (0.43%)  4 1/912 (0.11%)  1
LARYNGITIS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
LOWER RESPIRATORY TRACT INFECTION  1  2/926 (0.22%)  2 1/912 (0.11%)  1
MASTITIS  1  8/926 (0.86%)  9 0/912 (0.00%)  0
NEUTROPENIC SEPSIS  1  7/926 (0.76%)  8 1/912 (0.11%)  1
PAROTITIS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
PHARYNGITIS  1  1/926 (0.11%)  1 1/912 (0.11%)  1
PNEUMONIA  1  12/926 (1.30%)  12 12/912 (1.32%)  12
POST PROCEDURAL INFECTION  1  0/926 (0.00%)  0 1/912 (0.11%)  2
POSTOPERATIVE WOUND INFECTION  1  2/926 (0.22%)  3 0/912 (0.00%)  0
PULMONARY SEPSIS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
PYELONEPHRITIS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
RESPIRATORY TRACT INFECTION  1  3/926 (0.32%)  3 2/912 (0.22%)  2
RESPIRATORY TRACT INFECTION VIRAL  1  0/926 (0.00%)  0 1/912 (0.11%)  1
SEPSIS  1  1/926 (0.11%)  1 3/912 (0.33%)  3
SEPTIC SHOCK  1  1/926 (0.11%)  1 0/912 (0.00%)  0
SINUSITIS  1  1/926 (0.11%)  1 1/912 (0.11%)  1
SKIN INFECTION  1  0/926 (0.00%)  0 1/912 (0.11%)  1
SUBCUTANEOUS ABSCESS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
TONSILLITIS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
UPPER RESPIRATORY TRACT INFECTION  1  3/926 (0.32%)  3 2/912 (0.22%)  2
URINARY TRACT INFECTION  1  6/926 (0.65%)  6 8/912 (0.88%)  8
VASCULAR DEVICE INFECTION  1  1/926 (0.11%)  1 2/912 (0.22%)  2
VESTIBULAR NEURONITIS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
VIRAL INFECTION  1  1/926 (0.11%)  1 1/912 (0.11%)  1
VIRAL PHARYNGITIS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
WOUND INFECTION  1  0/926 (0.00%)  0 1/912 (0.11%)  1
Injury, poisoning and procedural complications     
ANKLE FRACTURE  1  2/926 (0.22%)  2 0/912 (0.00%)  0
FALL  1  1/926 (0.11%)  1 0/912 (0.00%)  0
FEMORAL NECK FRACTURE  1  0/926 (0.00%)  0 1/912 (0.11%)  1
HAND FRACTURE  1  0/926 (0.00%)  0 1/912 (0.11%)  1
HIP FRACTURE  1  1/926 (0.11%)  1 0/912 (0.00%)  0
HUMERUS FRACTURE  1  1/926 (0.11%)  1 0/912 (0.00%)  0
INFLAMMATION OF WOUND  1  0/926 (0.00%)  0 1/912 (0.11%)  1
INFUSION RELATED REACTION  1  2/926 (0.22%)  2 9/912 (0.99%)  9
JOINT DISLOCATION  1  1/926 (0.11%)  2 0/912 (0.00%)  0
LIGAMENT SPRAIN  1  1/926 (0.11%)  1 0/912 (0.00%)  0
OVERDOSE  1  0/926 (0.00%)  0 2/912 (0.22%)  2
POSTOPERATIVE WOUND COMPLICATION  1  0/926 (0.00%)  0 1/912 (0.11%)  1
RADIATION PNEUMONITIS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
RADIATION SKIN INJURY  1  0/926 (0.00%)  0 1/912 (0.11%)  1
ROAD TRAFFIC ACCIDENT  1  0/926 (0.00%)  0 1/912 (0.11%)  1
SEROMA  1  1/926 (0.11%)  1 1/912 (0.11%)  2
SPINAL COMPRESSION FRACTURE  1  1/926 (0.11%)  1 0/912 (0.00%)  0
THERMAL BURN  1  0/926 (0.00%)  0 1/912 (0.11%)  1
VASCULAR ACCESS COMPLICATION  1  1/926 (0.11%)  1 1/912 (0.11%)  1
WRIST FRACTURE  1  1/926 (0.11%)  1 1/912 (0.11%)  1
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  0/926 (0.00%)  0 1/912 (0.11%)  1
BLOOD CREATINE INCREASED  1  1/926 (0.11%)  1 0/912 (0.00%)  0
BLOOD PRESSURE DECREASED  1  1/926 (0.11%)  1 0/912 (0.00%)  0
ELECTROCARDIOGRAM REPOLARISATION ABNORMALITY  1  1/926 (0.11%)  1 0/912 (0.00%)  0
N-TERMINAL PROHORMONE BRAIN NATRIURETIC PEPTIDE INCREASED  1  1/926 (0.11%)  1 0/912 (0.00%)  0
NEUTROPHIL COUNT DECREASED  1  3/926 (0.32%)  3 0/912 (0.00%)  0
PLATELET COUNT DECREASED  1  0/926 (0.00%)  0 4/912 (0.44%)  4
WHITE BLOOD CELL COUNT DECREASED  1  1/926 (0.11%)  1 1/912 (0.11%)  1
Metabolism and nutrition disorders     
DECREASED APPETITE  1  1/926 (0.11%)  2 0/912 (0.00%)  0
DEHYDRATION  1  7/926 (0.76%)  8 2/912 (0.22%)  2
HYPERCREATININAEMIA  1  0/926 (0.00%)  0 1/912 (0.11%)  1
HYPERGLYCAEMIA  1  0/926 (0.00%)  0 1/912 (0.11%)  1
HYPOGLYCAEMIA  1  0/926 (0.00%)  0 1/912 (0.11%)  1
HYPOKALAEMIA  1  0/926 (0.00%)  0 1/912 (0.11%)  1
METABOLIC ACIDOSIS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  2/926 (0.22%)  2 0/912 (0.00%)  0
BACK PAIN  1  1/926 (0.11%)  1 0/912 (0.00%)  0
GROIN PAIN  1  1/926 (0.11%)  1 0/912 (0.00%)  0
INTERVERTEBRAL DISC PROTRUSION  1  1/926 (0.11%)  2 0/912 (0.00%)  0
MUSCLE SPASMS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
MUSCULOSKELETAL CHEST PAIN  1  0/926 (0.00%)  0 1/912 (0.11%)  1
OSTEOARTHRITIS  1  1/926 (0.11%)  2 0/912 (0.00%)  0
OSTEONECROSIS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
PAIN IN EXTREMITY  1  0/926 (0.00%)  0 1/912 (0.11%)  1
SPONDYLOLISTHESIS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
ACUTE PROMYELOCYTIC LEUKAEMIA  1  1/926 (0.11%)  1 0/912 (0.00%)  0
COLON NEOPLASM  1  0/926 (0.00%)  0 1/912 (0.11%)  1
FIBROMA  1  1/926 (0.11%)  1 0/912 (0.00%)  0
HAEMANGIOMA OF SKIN  1  0/926 (0.00%)  0 1/912 (0.11%)  1
UTERINE LEIOMYOMA  1  1/926 (0.11%)  1 0/912 (0.00%)  0
UTERINE LEIOMYOSARCOMA  1  1/926 (0.11%)  1 0/912 (0.00%)  0
Nervous system disorders     
CEREBRAL ISCHAEMIA  1  1/926 (0.11%)  1 1/912 (0.11%)  1
DEMENTIA  1  1/926 (0.11%)  1 0/912 (0.00%)  0
DIZZINESS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
HEADACHE  1  1/926 (0.11%)  1 0/912 (0.00%)  0
HYPOAESTHESIA  1  0/926 (0.00%)  0 1/912 (0.11%)  1
INTRACRANIAL ANEURYSM  1  0/926 (0.00%)  0 1/912 (0.11%)  1
LACUNAR INFARCTION  1  1/926 (0.11%)  1 0/912 (0.00%)  0
METABOLIC ENCEPHALOPATHY  1  0/926 (0.00%)  0 1/912 (0.11%)  1
MIGRAINE WITH AURA  1  0/926 (0.00%)  0 1/912 (0.11%)  1
SEIZURE  1  1/926 (0.11%)  1 0/912 (0.00%)  0
SYNCOPE  1  0/926 (0.00%)  0 2/912 (0.22%)  2
TENSION HEADACHE  1  1/926 (0.11%)  1 0/912 (0.00%)  0
Product Issues     
DEVICE BREAKAGE  1  0/926 (0.00%)  0 1/912 (0.11%)  1
Psychiatric disorders     
ANXIETY  1  1/926 (0.11%)  1 0/912 (0.00%)  0
DEPRESSION  1  1/926 (0.11%)  1 2/912 (0.22%)  2
SUICIDE ATTEMPT  1  1/926 (0.11%)  1 0/912 (0.00%)  0
Renal and urinary disorders     
RENAL COLIC  1  0/926 (0.00%)  0 1/912 (0.11%)  1
RENAL FAILURE  1  1/926 (0.11%)  1 0/912 (0.00%)  0
Reproductive system and breast disorders     
BREAST NECROSIS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
ENDOMETRIAL HYPERPLASIA  1  0/926 (0.00%)  0 1/912 (0.11%)  1
FIBROCYSTIC BREAST DISEASE  1  1/926 (0.11%)  1 0/912 (0.00%)  0
METRORRHAGIA  1  0/926 (0.00%)  0 1/912 (0.11%)  1
UTERINE CYST  1  0/926 (0.00%)  0 1/912 (0.11%)  1
VAGINAL HAEMORRHAGE  1  0/926 (0.00%)  0 1/912 (0.11%)  1
Respiratory, thoracic and mediastinal disorders     
BRONCHOSPASM  1  1/926 (0.11%)  1 0/912 (0.00%)  0
DYSPNOEA  1  2/926 (0.22%)  2 3/912 (0.33%)  3
EPISTAXIS  1  1/926 (0.11%)  1 3/912 (0.33%)  4
HYDROTHORAX  1  1/926 (0.11%)  1 0/912 (0.00%)  0
INTERSTITIAL LUNG DISEASE  1  1/926 (0.11%)  1 0/912 (0.00%)  0
OROPHARYNGEAL PAIN  1  1/926 (0.11%)  1 1/912 (0.11%)  1
PLEURAL EFFUSION  1  1/926 (0.11%)  1 0/912 (0.00%)  0
PNEUMONITIS  1  2/926 (0.22%)  2 3/912 (0.33%)  3
PNEUMOTHORAX  1  0/926 (0.00%)  0 1/912 (0.11%)  1
PULMONARY EMBOLISM  1  5/926 (0.54%)  5 0/912 (0.00%)  0
RESPIRATORY TRACT HAEMORRHAGE  1  0/926 (0.00%)  0 1/912 (0.11%)  1
SINUS PAIN  1  1/926 (0.11%)  1 0/912 (0.00%)  0
Skin and subcutaneous tissue disorders     
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME  1  1/926 (0.11%)  1 0/912 (0.00%)  0
RASH  1  1/926 (0.11%)  1 1/912 (0.11%)  1
SPIDER NAEVUS  1  0/926 (0.00%)  0 1/912 (0.11%)  1
Vascular disorders     
DEEP VEIN THROMBOSIS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
EMBOLISM  1  1/926 (0.11%)  1 1/912 (0.11%)  1
HAEMATOMA  1  0/926 (0.00%)  0 1/912 (0.11%)  1
HYPERTENSION  1  1/926 (0.11%)  1 1/912 (0.11%)  1
HYPOTENSION  1  2/926 (0.22%)  2 0/912 (0.00%)  0
SUBCLAVIAN VEIN THROMBOSIS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
VENOUS THROMBOSIS  1  1/926 (0.11%)  1 0/912 (0.00%)  0
VENOUS THROMBOSIS LIMB  1  1/926 (0.11%)  1 0/912 (0.00%)  0
1
Term from vocabulary, MedDRA version 22.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   902/926 (97.41%)      902/912 (98.90%)    
Blood and lymphatic system disorders     
ANAEMIA  1  184/926 (19.87%)  249 174/912 (19.08%)  243
LEUKOPENIA  1  73/926 (7.88%)  134 51/912 (5.59%)  96
NEUTROPENIA  1  232/926 (25.05%)  411 220/912 (24.12%)  403
THROMBOCYTOPENIA  1  25/926 (2.70%)  29 162/912 (17.76%)  298
Eye disorders     
DRY EYE  1  62/926 (6.70%)  69 75/912 (8.22%)  87
LACRIMATION INCREASED  1  112/926 (12.10%)  120 73/912 (8.00%)  75
VISION BLURRED  1  42/926 (4.54%)  44 46/912 (5.04%)  49
Gastrointestinal disorders     
ABDOMINAL PAIN  1  83/926 (8.96%)  103 86/912 (9.43%)  110
ABDOMINAL PAIN UPPER  1  82/926 (8.86%)  89 87/912 (9.54%)  109
CONSTIPATION  1  287/926 (30.99%)  369 299/912 (32.79%)  413
DIARRHOEA  1  605/926 (65.33%)  1158 405/912 (44.41%)  759
DRY MOUTH  1  63/926 (6.80%)  68 105/912 (11.51%)  116
DYSPEPSIA  1  123/926 (13.28%)  146 106/912 (11.62%)  123
GASTROOESOPHAGEAL REFLUX DISEASE  1  58/926 (6.26%)  64 39/912 (4.28%)  41
GINGIVAL BLEEDING  1  6/926 (0.65%)  6 57/912 (6.25%)  64
HAEMORRHOIDS  1  58/926 (6.26%)  71 46/912 (5.04%)  50
NAUSEA  1  596/926 (64.36%)  1034 605/912 (66.34%)  1246
STOMATITIS  1  276/926 (29.81%)  441 228/912 (25.00%)  338
VOMITING  1  243/926 (26.24%)  358 289/912 (31.69%)  502
General disorders     
ASTHENIA  1  121/926 (13.07%)  222 131/912 (14.36%)  254
CHILLS  1  40/926 (4.32%)  45 67/912 (7.35%)  79
FATIGUE  1  439/926 (47.41%)  672 419/912 (45.94%)  659
INFLUENZA LIKE ILLNESS  1  26/926 (2.81%)  33 62/912 (6.80%)  72
MALAISE  1  46/926 (4.97%)  63 60/912 (6.58%)  90
MUCOSAL INFLAMMATION  1  156/926 (16.85%)  213 111/912 (12.17%)  134
OEDEMA PERIPHERAL  1  156/926 (16.85%)  173 74/912 (8.11%)  91
PYREXIA  1  175/926 (18.90%)  242 227/912 (24.89%)  354
Infections and infestations     
CONJUNCTIVITIS  1  49/926 (5.29%)  51 42/912 (4.61%)  44
NASOPHARYNGITIS  1  175/926 (18.90%)  269 169/912 (18.53%)  255
PARONYCHIA  1  53/926 (5.72%)  59 50/912 (5.48%)  54
UPPER RESPIRATORY TRACT INFECTION  1  139/926 (15.01%)  197 126/912 (13.82%)  177
URINARY TRACT INFECTION  1  73/926 (7.88%)  99 63/912 (6.91%)  82
Injury, poisoning and procedural complications     
INFUSION RELATED REACTION  1  115/926 (12.42%)  132 126/912 (13.82%)  157
RADIATION SKIN INJURY  1  207/926 (22.35%)  210 205/912 (22.48%)  213
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  108/926 (11.66%)  134 300/912 (32.89%)  417
ASPARTATE AMINOTRANSFERASE INCREASED  1  98/926 (10.58%)  113 317/912 (34.76%)  431
BLOOD ALKALINE PHOSPHATASE INCREASED  1  20/926 (2.16%)  24 85/912 (9.32%)  100
BLOOD BILIRUBIN INCREASED  1  4/926 (0.43%)  6 80/912 (8.77%)  127
EJECTION FRACTION DECREASED  1  61/926 (6.59%)  72 28/912 (3.07%)  34
NEUTROPHIL COUNT DECREASED  1  83/926 (8.96%)  148 75/912 (8.22%)  135
PLATELET COUNT DECREASED  1  15/926 (1.62%)  21 143/912 (15.68%)  203
WEIGHT DECREASED  1  57/926 (6.16%)  61 79/912 (8.66%)  82
Metabolism and nutrition disorders     
DECREASED APPETITE  1  241/926 (26.03%)  348 244/912 (26.75%)  371
HYPOKALAEMIA  1  41/926 (4.43%)  50 67/912 (7.35%)  102
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  261/926 (28.19%)  342 237/912 (25.99%)  291
BACK PAIN  1  119/926 (12.85%)  136 92/912 (10.09%)  109
BONE PAIN  1  70/926 (7.56%)  94 56/912 (6.14%)  69
MUSCLE SPASMS  1  86/926 (9.29%)  92 97/912 (10.64%)  129
MUSCULOSKELETAL PAIN  1  67/926 (7.24%)  86 57/912 (6.25%)  70
MYALGIA  1  215/926 (23.22%)  257 153/912 (16.78%)  197
PAIN IN EXTREMITY  1  119/926 (12.85%)  153 114/912 (12.50%)  136
Nervous system disorders     
DIZZINESS  1  117/926 (12.63%)  140 105/912 (11.51%)  138
DYSGEUSIA  1  176/926 (19.01%)  200 159/912 (17.43%)  174
HEADACHE  1  234/926 (25.27%)  328 261/912 (28.62%)  419
NEUROPATHY PERIPHERAL  1  163/926 (17.60%)  203 140/912 (15.35%)  164
PARAESTHESIA  1  85/926 (9.18%)  102 101/912 (11.07%)  129
PERIPHERAL SENSORY NEUROPATHY  1  214/926 (23.11%)  236 194/912 (21.27%)  210
TASTE DISORDER  1  60/926 (6.48%)  72 63/912 (6.91%)  72
Psychiatric disorders     
ANXIETY  1  58/926 (6.26%)  63 42/912 (4.61%)  48
DEPRESSION  1  52/926 (5.62%)  54 53/912 (5.81%)  55
INSOMNIA  1  170/926 (18.36%)  203 155/912 (17.00%)  190
Reproductive system and breast disorders     
BREAST PAIN  1  45/926 (4.86%)  57 55/912 (6.03%)  65
Respiratory, thoracic and mediastinal disorders     
COUGH  1  148/926 (15.98%)  189 157/912 (17.21%)  190
DYSPNOEA  1  73/926 (7.88%)  87 79/912 (8.66%)  91
EPISTAXIS  1  182/926 (19.65%)  226 333/912 (36.51%)  487
OROPHARYNGEAL PAIN  1  111/926 (11.99%)  132 100/912 (10.96%)  123
RHINORRHOEA  1  77/926 (8.32%)  87 82/912 (8.99%)  96
Skin and subcutaneous tissue disorders     
ALOPECIA  1  630/926 (68.03%)  652 600/912 (65.79%)  618
DERMATITIS ACNEIFORM  1  52/926 (5.62%)  59 53/912 (5.81%)  60
DRY SKIN  1  132/926 (14.25%)  143 100/912 (10.96%)  112
ERYTHEMA  1  86/926 (9.29%)  100 75/912 (8.22%)  82
NAIL DISCOLOURATION  1  103/926 (11.12%)  103 76/912 (8.33%)  78
NAIL DISORDER  1  72/926 (7.78%)  76 43/912 (4.71%)  43
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME  1  66/926 (7.13%)  74 25/912 (2.74%)  31
PRURITUS  1  169/926 (18.25%)  222 126/912 (13.82%)  151
RASH  1  250/926 (27.00%)  354 214/912 (23.46%)  290
RASH MACULO-PAPULAR  1  47/926 (5.08%)  56 42/912 (4.61%)  59
Vascular disorders     
HOT FLUSH  1  167/926 (18.03%)  190 100/912 (10.96%)  110
HYPERTENSION  1  36/926 (3.89%)  51 63/912 (6.91%)  83
LYMPHOEDEMA  1  68/926 (7.34%)  70 30/912 (3.29%)  31
1
Term from vocabulary, MedDRA version 22.1
Indicates events were collected by systematic assessment
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
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01966471    
Other Study ID Numbers: BO28407
2012-004902-82 ( EudraCT Number )
First Submitted: October 17, 2013
First Posted: October 21, 2013
Results First Submitted: November 17, 2020
Results First Posted: January 12, 2021
Last Update Posted: June 28, 2021