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

• ClinicalTrials.gov Identifier: NCT01966471
• Recruitment Status: Completed
• First Posted: October 21, 2013
• Results First Posted: January 12, 2021
• Last Update Posted: June 14, 2022
• Sponsor: Hoffmann-La Roche
• 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

Participant Flow

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
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	0	0 [1]
Not Completed	918	928
Reason Not Completed
Death	44	56
Lost to Follow-up	46	39
Various reasons	4	4
Physician Decision	7	5
Study Terminated By Sponsor	758	773
Withdrawal by Subject	59	51
[1] There is a difference in the death count displayed here and in the All-Cause Mortality section under Adverse Events. The difference relates to a participant that died and who was randomized to the AC-KP arm, but never received trastuzumab emtansine. Consequently they were assigned to the AC-THP for safety analyses. This death counts in the AC-KP arm when summary is based on the ITT population, but counts in the AC-THP arm when the summary on the safety population.

Baseline Characteristics

Arm/Group Title		Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab	Total
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
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%

Outcome Measures

1. Primary Outcome

Title	Invasive Disease-Free Survival (IDFS) in the Node-Positive Subpopulation
Description	IDFS event was defined as the time from randomization until the date of first occurrence of one of the following: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer [bc] involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive bc recurrence (an invasive bc in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); Contralateral or ipsilateral second primary invasive bc; Distant recurrence (evidence of bc in any anatomic site [other than the three sites mentioned above]) that has either been histologically confirmed or clinically/radiographically diagnosed as recurrent invasive bc; Death attributable to any cause, including bc, non-bc, or unknown cause. 3-year IDFS event-free rate per randomized treatment arms in the ITT population was estimated using the Kaplan-Meier method and estimated the probability of a participant being event-free after 3 years after randomization.
Time Frame	Last 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.

Outcome Measure Data

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
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)

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
Description	IDFS event was defined as the time from randomization until the date of first occurrence of one of the following: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer [bc] involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive bc recurrence (an invasive bc in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); Contralateral or ipsilateral second primary invasive bc; Distant recurrence (evidence of bc in any anatomic site [other than the three sites mentioned above]) that has either been histologically confirmed or clinically/radiographically diagnosed as recurrent invasive bc; Death attributable to any cause, including bc, non-bc, or unknown cause. 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 up to approximately 7.5 years

Outcome Measure Data

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
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)	93.06; (91.40 to 94.73)

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	0.9291
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.01
	Confidence Interval	95%; 0.77 to 1.34
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	IDFS Plus Second Primary Non-Breast Cancer
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).
Time Frame	Baseline up to approximately 70 months

Outcome Measure Data

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
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
	93.43; (91.79 to 95.06)	92.26; (90.51 to 94.02)

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	0.8756
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.98
	Confidence Interval	95%; 0.74 to 1.30
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Disease-Free Survival (DFS)
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).
Time Frame	Baseline up to approximately 70 months

Outcome Measure Data

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
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
	93.32; (91.67 to 94.97)	92.04; (90.26 to 93.81)

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	0.9341
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	95%; 0.75 to 1.31
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Distant Recurrence-Free Interval (DRFI)
Description	DRFI was defined as time between randomization and first occurrence of distant breast cancer recurrence.
Time Frame	Baseline up to approximately 70 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
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
	95.23; (93.82 to 96.64)	94.91; (93.46 to 96.36)

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	0.4577
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.88
	Confidence Interval	95%; 0.61 to 1.25
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from randomization to death due to any cause.
Time Frame	First participant randomized up to approximately 7.5 years

Outcome Measure Data

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
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
	96.03; (94.72 to 97.34)	94.86; (93.40 to 96.32)

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	0.2864
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.24
	Confidence Interval	95%; 0.83 to 1.84
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Percentage of Participants With Adverse Events
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 approximately 7.5 years

Outcome Measure Data

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
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
Description	LVEF was assessed using either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans.
Time Frame	First participant randomized up to approximately 7.5 years.

Outcome Measure Data

Analysis Population Description

The safety population included all randomized participants who received at least one full or partial dose of any study treatment.

Arm/Group Title		Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab
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: Count of Participants; Unit of Measure: Participants
Decrease from baseline <10 Ejection Fraction (EF) points	Number Analyzed	914 participants	912 participants
		506 55.4%	522 57.2%
Absolute value >= 50% and decrease from baseline >= 10 EF points	Number Analyzed	914 participants	912 participants
		254 27.8%	245 26.9%
Absolute value < 50% and decrease from baseline >= 10 EF points	Number Analyzed	914 participants	912 participants
		71 7.8%	35 3.8%
Absolute value < 50% and decrease from baseline >= 15 EF points	Number Analyzed	914 participants	912 participants
		61 6.7%	28 3.1%

9. Secondary Outcome

Title	European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
Description	The time to clinically meaningful deterioration in the global health status/Quality of life and Functional (Physical, Role, and Cognitive) subscales of the the QLQ-C30 was assessed from the time of the HER2-Targeted treatment to the worsening in the respective scales. 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.

Outcome Measure Data

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
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.

Adverse Events

Time Frame	From randomization to approximately 7.5 years
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
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	45/926 (4.86%)		55/912 (6.03%)
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
Biliary 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	4/912 (0.44%)	4
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	1/912 (0.11%)	1
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%)	1
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 myeloid leukaemia † 1	0/926 (0.00%)	0	1/912 (0.11%)	1
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	1/912 (0.11%)	1
Major depression † 1	0/926 (0.00%)	0	1/912 (0.11%)	1
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
Intermenstrual bleeding † 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 24.0; † Indicates events were collected by systematic assessment
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%)	297
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	83/926 (8.96%)	90	87/912 (9.54%)	110
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	42/926 (4.54%)	58	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%)	353
Infections and infestations
Conjunctivitis † 1	49/926 (5.29%)	51	42/912 (4.61%)	44
Nasopharyngitis † 1	175/926 (18.90%)	269	171/912 (18.75%)	257
Paronychia † 1	53/926 (5.72%)	59	50/912 (5.48%)	54
Upper respiratory tract infection † 1	139/926 (15.01%)	197	125/912 (13.71%)	176
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	301/912 (33.00%)	418
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	29/912 (3.18%)	35
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	289/926 (31.21%)	397	261/912 (28.62%)	338
Back pain † 1	120/926 (12.96%)	138	93/912 (10.20%)	111
Bone pain † 1	70/926 (7.56%)	94	58/912 (6.36%)	71
Muscle spasms † 1	86/926 (9.29%)	92	97/912 (10.64%)	129
Myalgia † 1	214/926 (23.11%)	255	152/912 (16.67%)	195
Pain in extremity † 1	119/926 (12.85%)	154	114/912 (12.50%)	136
Nervous system disorders
Dizziness † 1	117/926 (12.63%)	140	105/912 (11.51%)	138
Dysgeusia † 1	180/926 (19.44%)	205	162/912 (17.76%)	177
Headache † 1	234/926 (25.27%)	328	261/912 (28.62%)	419
Neuropathy peripheral † 1	163/926 (17.60%)	204	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	193/912 (21.16%)	209
Taste disorder † 1	56/926 (6.05%)	67	60/912 (6.58%)	69
Psychiatric disorders
Anxiety † 1	58/926 (6.26%)	63	42/912 (4.61%)	48
Depression † 1	52/926 (5.62%)	54	52/912 (5.70%)	54
Insomnia † 1	171/926 (18.47%)	204	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	629/926 (67.93%)	651	598/912 (65.57%)	616
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	104/926 (11.23%)	104	76/912 (8.33%)	78
Nail disorder † 1	68/926 (7.34%)	72	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	249/926 (26.89%)	353	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 24.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. doi: 10.1200/JCO.21.00896. Epub 2021 Dec 10.

• 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 14, 2022