Trial Outcomes & Findings for 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 (NCT NCT01966471)

NCT ID: NCT01966471

Last Updated: 2022-06-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1846 participants

Primary outcome timeframe

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.

Results posted on

2022-06-14

Participant Flow

The study was conducted at 288 centers in 36 countries.

Randomization was stratified according to geographic region, nodal status, centrally assessed hormonal receptor status and type of anthracycline.

Participant milestones

Participant milestones
Measure	Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane 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.	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab 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 Study STARTED	918	928
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	918	928

Reasons for withdrawal

Reasons for withdrawal
Measure	Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane 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.	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab 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 Study Death	44	56
Overall Study Lost to Follow-up	46	39
Overall Study Various reasons	4	4
Overall Study Physician Decision	7	5
Overall Study Study Terminated By Sponsor	758	773
Overall Study Withdrawal by Subject	59	51

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane n=918 Participants 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.	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab n=928 Participants 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 n=1846 Participants Total of all reporting groups
Age, Continuous	51.6 years STANDARD_DEVIATION 10.8 • n=93 Participants	51.9 years STANDARD_DEVIATION 10.8 • n=4 Participants	51.7 years STANDARD_DEVIATION 10.8 • n=27 Participants
Sex: Female, Male Female	913 Participants n=93 Participants	926 Participants n=4 Participants	1839 Participants n=27 Participants
Sex: Female, Male Male	5 Participants n=93 Participants	2 Participants n=4 Participants	7 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	70 Participants n=93 Participants	68 Participants n=4 Participants	138 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	798 Participants n=93 Participants	790 Participants n=4 Participants	1588 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	50 Participants n=93 Participants	70 Participants n=4 Participants	120 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	12 Participants n=93 Participants	12 Participants n=4 Participants	24 Participants n=27 Participants
Race (NIH/OMB) Asian	267 Participants n=93 Participants	275 Participants n=4 Participants	542 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Black or African American	15 Participants n=93 Participants	8 Participants n=4 Participants	23 Participants n=27 Participants
Race (NIH/OMB) White	558 Participants n=93 Participants	565 Participants n=4 Participants	1123 Participants n=27 Participants
Race (NIH/OMB) More than one race	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	63 Participants n=93 Participants	65 Participants n=4 Participants	128 Participants n=27 Participants

PRIMARY outcome

Timeframe: 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.

Population: The ITT lymph node positive population was a subpopulation of the randomized participant population including patients with positive lymph node.

Outcome measures

Outcome measures
Measure	Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane n=826 Participants 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.	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab n=832 Participants 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.
Invasive Disease-Free Survival (IDFS) in the Node-Positive Subpopulation	94.10 Percent Probability Interval 92.46 to 95.73	92.75 Percent Probability Interval 90.95 to 94.54

PRIMARY outcome

Timeframe: First participant randomized up to approximately 7.5 years

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane n=918 Participants 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.	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab n=928 Participants 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.
Invasive Disease-Free Survival (IDFS) in the Overall Population	94.22 Percent Probability Interval 92.68 to 95.76	93.06 Percent Probability Interval 91.4 to 94.73

SECONDARY outcome

Timeframe: Baseline up to approximately 70 months

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).

Outcome measures

Outcome measures
Measure	Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane n=918 Participants 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.	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab n=928 Participants 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.
IDFS Plus Second Primary Non-Breast Cancer	93.43 Percent Probability Interval 91.79 to 95.06	92.26 Percent Probability Interval 90.51 to 94.02

SECONDARY outcome

Timeframe: Baseline up to approximately 70 months

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).

Outcome measures

Outcome measures
Measure	Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane n=918 Participants 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.	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab n=928 Participants 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.
Disease-Free Survival (DFS)	93.32 Percent Probability Interval 91.67 to 94.97	92.04 Percent Probability Interval 90.26 to 93.81

SECONDARY outcome

Timeframe: Baseline up to approximately 70 months

DRFI was defined as time between randomization and first occurrence of distant breast cancer recurrence.

Outcome measures

Outcome measures
Measure	Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane n=918 Participants 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.	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab n=928 Participants 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.
Distant Recurrence-Free Interval (DRFI)	95.23 Percent Probability Interval 93.82 to 96.64	94.91 Percent Probability Interval 93.46 to 96.36

SECONDARY outcome

Timeframe: First participant randomized up to approximately 7.5 years

OS was defined as the time from randomization to death due to any cause.

Outcome measures

Outcome measures
Measure	Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane n=918 Participants 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.	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab n=928 Participants 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 Survival (OS)	96.03 Percent Probability Interval 94.72 to 97.34	94.86 Percent Probability Interval 93.4 to 96.32

SECONDARY outcome

Timeframe: From randomization to approximately 7.5 years

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane n=926 Participants 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.	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab n=912 Participants 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.
Percentage of Participants With Adverse Events	98.5 Percentage of participants	99.1 Percentage of participants

SECONDARY outcome

Timeframe: First participant randomized up to approximately 7.5 years.

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

LVEF was assessed using either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans.

Outcome measures

Outcome measures
Measure	Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane n=926 Participants 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.	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab n=912 Participants 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.
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) From Baseline Over Time Absolute value < 50% and decrease from baseline >= 15 EF points	61 Participants	28 Participants
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) From Baseline Over Time Decrease from baseline <10 Ejection Fraction (EF) points	506 Participants	522 Participants
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) From Baseline Over Time Absolute value >= 50% and decrease from baseline >= 10 EF points	254 Participants	245 Participants
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) From Baseline Over Time Absolute value < 50% and decrease from baseline >= 10 EF points	71 Participants	35 Participants

SECONDARY outcome

Timeframe: Baseline, Cycles 1, 2, 3, 4, 5, 9, 14, End of Treatment, Follow-up Month 6, Follow-up Month 12, Follow-up Month 18

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane n=869 Participants 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.	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab n=891 Participants 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.
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 2: Appetite Loss	15.2 Units on a Scale Standard Deviation 27.7	13.1 Units on a Scale Standard Deviation 26.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline: Appetite Loss	8.2 Units on a Scale Standard Deviation 17.6	7.6 Units on a Scale Standard Deviation 16.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 1: Appetite Loss	12.2 Units on a Scale Standard Deviation 27.9	10.8 Units on a Scale Standard Deviation 26.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 3: Appetite Loss	14.3 Units on a Scale Standard Deviation 28.2	10.3 Units on a Scale Standard Deviation 25.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 4: Appetite Loss	16.2 Units on a Scale Standard Deviation 29.8	9.4 Units on a Scale Standard Deviation 25.5
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 5: Appetite Loss	12.0 Units on a Scale Standard Deviation 28.4	9.0 Units on a Scale Standard Deviation 26.2
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 9: Appetite Loss	5.7 Units on a Scale Standard Deviation 23.9	8.2 Units on a Scale Standard Deviation 25.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 14: Appetite Loss	2.2 Units on a Scale Standard Deviation 23.1	6.4 Units on a Scale Standard Deviation 25.4
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at EoT: Appetite Loss	0.5 Units on a Scale Standard Deviation 22.3	5.6 Units on a Scale Standard Deviation 25.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 6: Appetite Loss	-1.3 Units on a Scale Standard Deviation 20.7	-2.4 Units on a Scale Standard Deviation 20.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 12: Appetite Loss	-2.2 Units on a Scale Standard Deviation 20.8	-2.3 Units on a Scale Standard Deviation 20.5
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 18: Appetite Loss	—	-16.7 Units on a Scale Standard Deviation 23.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline: Constipation	9.6 Units on a Scale Standard Deviation 19.4	9.0 Units on a Scale Standard Deviation 19.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 1: Constipation	8.4 Units on a Scale Standard Deviation 22.5	8.0 Units on a Scale Standard Deviation 26.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 2: Constipation	1.1 Units on a Scale Standard Deviation 25.0	0.9 Units on a Scale Standard Deviation 23.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 3: Constipation	2.0 Units on a Scale Standard Deviation 24.6	0.2 Units on a Scale Standard Deviation 22.2
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 4: Constipation	2.5 Units on a Scale Standard Deviation 24.3	-0.6 Units on a Scale Standard Deviation 23.2
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 5: Constipation	0.5 Units on a Scale Standard Deviation 22.4	-0.4 Units on a Scale Standard Deviation 22.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 9: Constipation	-0.7 Units on a Scale Standard Deviation 21.7	3.3 Units on a Scale Standard Deviation 24.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 14: Constipation	0.6 Units on a Scale Standard Deviation 21.1	4.2 Units on a Scale Standard Deviation 24.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at EoT: Constipation	0.2 Units on a Scale Standard Deviation 21.8	4.7 Units on a Scale Standard Deviation 25.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 6: Constipation	3.4 Units on a Scale Standard Deviation 23.2	1.5 Units on a Scale Standard Deviation 24.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 12: Constipation	2.8 Units on a Scale Standard Deviation 22.8	2.0 Units on a Scale Standard Deviation 23.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 18: Constipation	—	0.0 Units on a Scale Standard Deviation 0.0
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline: Diarrhea	5.2 Units on a Scale Standard Deviation 13.2	4.7 Units on a Scale Standard Deviation 12.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 1: Diarrhea	4.7 Units on a Scale Standard Deviation 20.3	4.2 Units on a Scale Standard Deviation 18.4
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 2: Diarrhea	32.5 Units on a Scale Standard Deviation 32.8	16.0 Units on a Scale Standard Deviation 26.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 3: Diarrhea	28.4 Units on a Scale Standard Deviation 30.5	11.3 Units on a Scale Standard Deviation 23.5
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 4: Diarrhea	26.5 Units on a Scale Standard Deviation 30.0	10.3 Units on a Scale Standard Deviation 23.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 5: Diarrhea	23.9 Units on a Scale Standard Deviation 30.4	8.8 Units on a Scale Standard Deviation 22.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 9: Diarrhea	12.6 Units on a Scale Standard Deviation 24.6	4.7 Units on a Scale Standard Deviation 21.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 14: Diarrhea	12.5 Units on a Scale Standard Deviation 26.4	5.1 Units on a Scale Standard Deviation 20.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at EoT: Diarrhea	10.3 Units on a Scale Standard Deviation 25.2	3.0 Units on a Scale Standard Deviation 19.4
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 6: Diarrhea	-0.3 Units on a Scale Standard Deviation 16.4	-1.1 Units on a Scale Standard Deviation 16.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 12: Diarrhea	-0.3 Units on a Scale Standard Deviation 17.8	0.0 Units on a Scale Standard Deviation 17.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 18: Diarrhea	—	-16.7 Units on a Scale Standard Deviation 23.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline: Dyspnea	5.8 Units on a Scale Standard Deviation 14.0	6.2 Units on a Scale Standard Deviation 14.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 1: Dyspnea	10.4 Units on a Scale Standard Deviation 21.4	9.2 Units on a Scale Standard Deviation 21.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 2: Dyspnea	11.6 Units on a Scale Standard Deviation 22.0	7.4 Units on a Scale Standard Deviation 20.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 3: Dyspnea	13.4 Units on a Scale Standard Deviation 23.2	6.5 Units on a Scale Standard Deviation 20.5
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 4: Dyspnea	14.3 Units on a Scale Standard Deviation 23.7	5.9 Units on a Scale Standard Deviation 20.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 5: Dyspnea	13.7 Units on a Scale Standard Deviation 22.4	5.6 Units on a Scale Standard Deviation 19.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 9: Dyspnea	7.8 Units on a Scale Standard Deviation 19.3	7.5 Units on a Scale Standard Deviation 21.4
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 14: Dyspnea	6.8 Units on a Scale Standard Deviation 20.8	8.1 Units on a Scale Standard Deviation 21.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at EoT: Dyspnea	7.6 Units on a Scale Standard Deviation 21.1	8.8 Units on a Scale Standard Deviation 22.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 6: Dyspnea	7.0 Units on a Scale Standard Deviation 20.8	5.3 Units on a Scale Standard Deviation 19.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 12: Dyspnea	6.2 Units on a Scale Standard Deviation 20.9	5.8 Units on a Scale Standard Deviation 20.5
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 18: Dyspnea	—	-16.7 Units on a Scale Standard Deviation 23.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline: Fatigue	21.5 Units on a Scale Standard Deviation 18.6	20.6 Units on a Scale Standard Deviation 18.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 1: Fatigue	13.2 Units on a Scale Standard Deviation 21.5	14.4 Units on a Scale Standard Deviation 22.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 2: Fatigue	15.4 Units on a Scale Standard Deviation 22.7	11.2 Units on a Scale Standard Deviation 21.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 3: Fatigue	15.3 Units on a Scale Standard Deviation 23.1	8.7 Units on a Scale Standard Deviation 20.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 4: Fatigue	16.0 Units on a Scale Standard Deviation 23.4	8.2 Units on a Scale Standard Deviation 20.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 5: Fatigue	14.9 Units on a Scale Standard Deviation 22.8	8.4 Units on a Scale Standard Deviation 21.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 9: Fatigue	8.4 Units on a Scale Standard Deviation 22.0	9.8 Units on a Scale Standard Deviation 20.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 14: Fatigue	6.7 Units on a Scale Standard Deviation 22.0	10.6 Units on a Scale Standard Deviation 22.4
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at EoT: Fatigue	5.5 Units on a Scale Standard Deviation 22.9	9.3 Units on a Scale Standard Deviation 21.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 6: Fatigue	2.8 Units on a Scale Standard Deviation 21.9	3.1 Units on a Scale Standard Deviation 21.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 12: Fatigue	1.9 Units on a Scale Standard Deviation 22.1	1.8 Units on a Scale Standard Deviation 20.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 18: Fatigue	—	-5.6 Units on a Scale Standard Deviation 39.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline: Financial Difficulties	20.1 Units on a Scale Standard Deviation 28.3	19.9 Units on a Scale Standard Deviation 28.5
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 1: Financial Difficulties	2.2 Units on a Scale Standard Deviation 25.2	0.3 Units on a Scale Standard Deviation 24.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 2: Financial Difficulties	2.0 Units on a Scale Standard Deviation 25.7	-0.6 Units on a Scale Standard Deviation 25.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 3: Financial Difficulties	3.9 Units on a Scale Standard Deviation 24.7	-0.4 Units on a Scale Standard Deviation 25.0
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 4: Financial Difficulties	3.7 Units on a Scale Standard Deviation 24.9	-0.2 Units on a Scale Standard Deviation 25.4
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 5: Financial Difficulties	3.4 Units on a Scale Standard Deviation 25.3	0.7 Units on a Scale Standard Deviation 26.2
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 9: Financial Difficulties	0.9 Units on a Scale Standard Deviation 25.6	-0.5 Units on a Scale Standard Deviation 26.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 14: Financial Difficulties	-1.4 Units on a Scale Standard Deviation 25.1	-1.0 Units on a Scale Standard Deviation 27.2
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at EoT: Financial Difficulties	-1.1 Units on a Scale Standard Deviation 27.3	-1.7 Units on a Scale Standard Deviation 25.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 6: Financial Difficulties	-3.8 Units on a Scale Standard Deviation 27.4	-5.2 Units on a Scale Standard Deviation 28.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 12: Financial Difficulties	-5.1 Units on a Scale Standard Deviation 28.6	-6.8 Units on a Scale Standard Deviation 28.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 18: Financial Difficulties	—	0.0 Units on a Scale Standard Deviation 0.0
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline: Insomnia	23.9 Units on a Scale Standard Deviation 26.1	24.9 Units on a Scale Standard Deviation 27.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 1: Insomnia	3.6 Units on a Scale Standard Deviation 30.2	1.8 Units on a Scale Standard Deviation 28.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 2: Insomnia	6.0 Units on a Scale Standard Deviation 30.5	0.4 Units on a Scale Standard Deviation 30.0
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 3: Insomnia	6.2 Units on a Scale Standard Deviation 30.2	-0.1 Units on a Scale Standard Deviation 30.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 4: Insomnia	8.6 Units on a Scale Standard Deviation 31.3	1.1 Units on a Scale Standard Deviation 30.4
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 5: Insomnia	5.2 Units on a Scale Standard Deviation 31.1	1.1 Units on a Scale Standard Deviation 29.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 9: Insomnia	4.3 Units on a Scale Standard Deviation 30.5	1.1 Units on a Scale Standard Deviation 29.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 14: Insomnia	2.7 Units on a Scale Standard Deviation 30.6	2.7 Units on a Scale Standard Deviation 30.2
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at EoT: Insomnia	2.5 Units on a Scale Standard Deviation 30.8	0.9 Units on a Scale Standard Deviation 30.2
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 6: Insomnia	0.9 Units on a Scale Standard Deviation 29.5	-2.3 Units on a Scale Standard Deviation 29.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 12: Insomnia	0.0 Units on a Scale Standard Deviation 30.2	-2.9 Units on a Scale Standard Deviation 30.4
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 18: Insomnia	—	-16.7 Units on a Scale Standard Deviation 23.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline: Nausea/Vomiting	2.6 Units on a Scale Standard Deviation 9.4	2.3 Units on a Scale Standard Deviation 7.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 1: Nausea/Vomiting	10.4 Units on a Scale Standard Deviation 19.5	10.5 Units on a Scale Standard Deviation 17.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 2: Nausea/Vomiting	6.0 Units on a Scale Standard Deviation 16.5	7.5 Units on a Scale Standard Deviation 16.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 3: Nausea/Vomiting	5.0 Units on a Scale Standard Deviation 16.2	5.2 Units on a Scale Standard Deviation 13.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 4: Nausea/Vomiting	4.7 Units on a Scale Standard Deviation 16.0	3.7 Units on a Scale Standard Deviation 12.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 5: Nausea/Vomiting	4.0 Units on a Scale Standard Deviation 15.6	3.2 Units on a Scale Standard Deviation 13.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 9: Nausea/Vomiting	1.1 Units on a Scale Standard Deviation 13.8	2.8 Units on a Scale Standard Deviation 11.5
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 14: Nausea/Vomiting	1.1 Units on a Scale Standard Deviation 12.3	3.0 Units on a Scale Standard Deviation 12.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at EoT: Nausea/Vomiting	0.9 Units on a Scale Standard Deviation 13.2	1.7 Units on a Scale Standard Deviation 12.0
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 6: Nausea/Vomiting	0.2 Units on a Scale Standard Deviation 11.6	0.1 Units on a Scale Standard Deviation 10.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 12: Nausea/Vomiting	0.5 Units on a Scale Standard Deviation 12.4	0.6 Units on a Scale Standard Deviation 10.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 18: Nausea/Vomiting	—	-8.3 Units on a Scale Standard Deviation 11.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline: Pain	17.4 Units on a Scale Standard Deviation 20.1	16.4 Units on a Scale Standard Deviation 20.0
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 1: Pain	1.8 Units on a Scale Standard Deviation 22.8	1.1 Units on a Scale Standard Deviation 22.5
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 2: Pain	5.0 Units on a Scale Standard Deviation 24.5	2.8 Units on a Scale Standard Deviation 23.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 3: Pain	3.5 Units on a Scale Standard Deviation 23.7	2.5 Units on a Scale Standard Deviation 22.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 4: Pain	5.4 Units on a Scale Standard Deviation 23.2	3.1 Units on a Scale Standard Deviation 23.5
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 5: Pain	5.2 Units on a Scale Standard Deviation 23.7	3.8 Units on a Scale Standard Deviation 23.5
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 9: Pain	3.4 Units on a Scale Standard Deviation 22.6	3.9 Units on a Scale Standard Deviation 23.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 14: Pain	2.0 Units on a Scale Standard Deviation 23.4	5.7 Units on a Scale Standard Deviation 24.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at EoT: Pain	1.9 Units on a Scale Standard Deviation 23.3	5.1 Units on a Scale Standard Deviation 24.5
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 6: Pain	0.8 Units on a Scale Standard Deviation 23.0	1.4 Units on a Scale Standard Deviation 22.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 12: Pain	0.0 Units on a Scale Standard Deviation 23.3	0.5 Units on a Scale Standard Deviation 21.5
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 18: Pain	—	-25.0 Units on a Scale Standard Deviation 35.4
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline: Cognitive Functioning	88.6 Units on a Scale Standard Deviation 16.9	88.7 Units on a Scale Standard Deviation 16.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 1: Cognitive Functioning	-9.7 Units on a Scale Standard Deviation 20.8	-6.9 Units on a Scale Standard Deviation 19.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 2: Cognitive Functioning	-9.4 Units on a Scale Standard Deviation 20.0	-6.8 Units on a Scale Standard Deviation 19.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 3: Cognitive Functioning	-10.1 Units on a Scale Standard Deviation 20.8	-6.4 Units on a Scale Standard Deviation 19.4
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 4: Cognitive Functioning	-11.8 Units on a Scale Standard Deviation 21.6	-6.9 Units on a Scale Standard Deviation 19.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 5: Cognitive Functioning	-10.8 Units on a Scale Standard Deviation 21.6	-7.3 Units on a Scale Standard Deviation 20.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 9: Cognitive Functioning	-8.3 Units on a Scale Standard Deviation 20.2	-7.6 Units on a Scale Standard Deviation 20.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 14: Cognitive Functioning	-8.1 Units on a Scale Standard Deviation 20.3	-8.1 Units on a Scale Standard Deviation 20.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at EoT: Cognitive Functioning	-8.7 Units on a Scale Standard Deviation 22.3	-8.4 Units on a Scale Standard Deviation 20.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 6: Cognitive Functioning	-8.0 Units on a Scale Standard Deviation 20.4	-6.1 Units on a Scale Standard Deviation 19.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 12: Cognitive Functioning	-7.1 Units on a Scale Standard Deviation 22.5	-6.0 Units on a Scale Standard Deviation 20.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 18: Cognitive Functioning	—	16.7 Units on a Scale Standard Deviation 23.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline: Emotional Functioning	76.0 Units on a Scale Standard Deviation 19.7	75.7 Units on a Scale Standard Deviation 20.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 1: Emotional Functioning	-1.1 Units on a Scale Standard Deviation 20.3	0.0 Units on a Scale Standard Deviation 19.2
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 2: Emotional Functioning	-1.0 Units on a Scale Standard Deviation 20.8	1.6 Units on a Scale Standard Deviation 19.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 3: Emotional Functioning	-0.9 Units on a Scale Standard Deviation 21.2	2.2 Units on a Scale Standard Deviation 19.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 4: Emotional Functioning	-2.5 Units on a Scale Standard Deviation 22.3	2.8 Units on a Scale Standard Deviation 20.0
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 5: Emotional Functioning	-1.2 Units on a Scale Standard Deviation 22.2	2.6 Units on a Scale Standard Deviation 21.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 9: Emotional Functioning	3.1 Units on a Scale Standard Deviation 20.9	2.9 Units on a Scale Standard Deviation 21.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 14: Emotional Functioning	4.1 Units on a Scale Standard Deviation 21.0	2.5 Units on a Scale Standard Deviation 21.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at EoT: Emotional Functioning	3.0 Units on a Scale Standard Deviation 22.4	3.1 Units on a Scale Standard Deviation 21.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 6: Emotional Functioning	4.7 Units on a Scale Standard Deviation 21.2	6.1 Units on a Scale Standard Deviation 21.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 12: Emotional Functioning	5.8 Units on a Scale Standard Deviation 22.1	6.5 Units on a Scale Standard Deviation 21.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 18: Emotional Functioning	—	12.5 Units on a Scale Standard Deviation 17.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline: Physical Functioning	88.4 Units on a Scale Standard Deviation 13.5	89.1 Units on a Scale Standard Deviation 12.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 1: Physical Functioning	-6.0 Units on a Scale Standard Deviation 14.5	-5.9 Units on a Scale Standard Deviation 13.4
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 2: Physical Functioning	-7.8 Units on a Scale Standard Deviation 15.8	-4.8 Units on a Scale Standard Deviation 12.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 3: Physical Functioning	-7.1 Units on a Scale Standard Deviation 15.4	-4.1 Units on a Scale Standard Deviation 13.0
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 4: Physical Functioning	-8.4 Units on a Scale Standard Deviation 16.2	-3.5 Units on a Scale Standard Deviation 13.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 5: Physical Functioning	-8.3 Units on a Scale Standard Deviation 16.1	-3.5 Units on a Scale Standard Deviation 13.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 9: Physical Functioning	-4.0 Units on a Scale Standard Deviation 15.0	-3.8 Units on a Scale Standard Deviation 14.2
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 14: Physical Functioning	-2.7 Units on a Scale Standard Deviation 14.2	-4.2 Units on a Scale Standard Deviation 14.2
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at EoT: Physical Functioning	-2.2 Units on a Scale Standard Deviation 14.7	-4.9 Units on a Scale Standard Deviation 15.0
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 6: Physical Functioning	-0.6 Units on a Scale Standard Deviation 14.4	-1.6 Units on a Scale Standard Deviation 13.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 12: Physical Functioning	-0.1 Units on a Scale Standard Deviation 15.4	-0.8 Units on a Scale Standard Deviation 13.2
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 18: Physical Functioning	—	13.3 Units on a Scale Standard Deviation 18.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline: Role Functioning	83.1 Units on a Scale Standard Deviation 21.7	83.4 Units on a Scale Standard Deviation 21.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 1: Role Functioning	-5.1 Units on a Scale Standard Deviation 24.5	-5.7 Units on a Scale Standard Deviation 24.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 2: Role Functioning	-9.7 Units on a Scale Standard Deviation 26.6	-5.5 Units on a Scale Standard Deviation 24.0
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 3: Role Functioning	-8.9 Units on a Scale Standard Deviation 26.7	-2.7 Units on a Scale Standard Deviation 23.2
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 4: Role Functioning	-10.7 Units on a Scale Standard Deviation 27.5	-3.2 Units on a Scale Standard Deviation 23.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 5: Role Functioning	-9.4 Units on a Scale Standard Deviation 27.3	-3.5 Units on a Scale Standard Deviation 23.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 9: Role Functioning	-3.3 Units on a Scale Standard Deviation 25.4	-3.2 Units on a Scale Standard Deviation 24.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 14: Role Functioning	-0.5 Units on a Scale Standard Deviation 25.0	-4.3 Units on a Scale Standard Deviation 25.3
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at EoT: Role Functioning	-0.2 Units on a Scale Standard Deviation 26.3	-3.5 Units on a Scale Standard Deviation 24.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 6: Role Functioning	2.2 Units on a Scale Standard Deviation 24.7	2.4 Units on a Scale Standard Deviation 24.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 12: Role Functioning	2.6 Units on a Scale Standard Deviation 25.9	3.7 Units on a Scale Standard Deviation 23.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 18: Role Functioning	—	8.3 Units on a Scale Standard Deviation 11.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline: Social Functioning	83.0 Units on a Scale Standard Deviation 22.9	83.2 Units on a Scale Standard Deviation 21.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 1: Social Functioning	-8.0 Units on a Scale Standard Deviation 24.3	-5.3 Units on a Scale Standard Deviation 22.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 2: Social Functioning	-10.1 Units on a Scale Standard Deviation 26.1	-4.1 Units on a Scale Standard Deviation 23.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 3: Social Functioning	-9.5 Units on a Scale Standard Deviation 25.6	-3.3 Units on a Scale Standard Deviation 24.4
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 4: Social Functioning	-10.3 Units on a Scale Standard Deviation 26.3	-3.2 Units on a Scale Standard Deviation 24.2
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 5: Social Functioning	-8.7 Units on a Scale Standard Deviation 26.5	-2.6 Units on a Scale Standard Deviation 23.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 9: Social Functioning	-1.7 Units on a Scale Standard Deviation 25.1	-3.4 Units on a Scale Standard Deviation 24.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 14: Social Functioning	-0.1 Units on a Scale Standard Deviation 25.3	-2.4 Units on a Scale Standard Deviation 24.9
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at EoT: Social Functioning	0.3 Units on a Scale Standard Deviation 26.1	-1.6 Units on a Scale Standard Deviation 24.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 6: Social Functioning	3.3 Units on a Scale Standard Deviation 24.8	4.0 Units on a Scale Standard Deviation 24.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 12: Social Functioning	4.6 Units on a Scale Standard Deviation 25.2	6.4 Units on a Scale Standard Deviation 22.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 18: Social Functioning	—	33.3 Units on a Scale Standard Deviation 47.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline: Global Health Status	74.3 Units on a Scale Standard Deviation 18.7	73.9 Units on a Scale Standard Deviation 18.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 1: Global Health Status	-7.5 Units on a Scale Standard Deviation 20.1	-7.2 Units on a Scale Standard Deviation 20.4
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 2: Global Health Status	-12.4 Units on a Scale Standard Deviation 22.6	-7.1 Units on a Scale Standard Deviation 20.2
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 3: Global Health Status	-11.7 Units on a Scale Standard Deviation 20.6	-5.2 Units on a Scale Standard Deviation 19.1
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 4: Global Health Status	-12.7 Units on a Scale Standard Deviation 21.3	-5.5 Units on a Scale Standard Deviation 19.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 5: Global Health Status	-12.1 Units on a Scale Standard Deviation 21.7	-5.8 Units on a Scale Standard Deviation 19.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 9: Global Health Status	-5.9 Units on a Scale Standard Deviation 20.1	-6.4 Units on a Scale Standard Deviation 20.6
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at Cycle 14: Global Health Status	-3.9 Units on a Scale Standard Deviation 21.1	-6.3 Units on a Scale Standard Deviation 20.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at EoT: Global Health Status	-3.5 Units on a Scale Standard Deviation 21.3	-4.9 Units on a Scale Standard Deviation 20.7
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 6: Global Health Status	-0.6 Units on a Scale Standard Deviation 21.3	0.3 Units on a Scale Standard Deviation 21.4
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 12: Global Health Status	-0.2 Units on a Scale Standard Deviation 21.9	1.2 Units on a Scale Standard Deviation 20.8
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Change at FU Month 18: Global Health Status	—	16.7 Units on a Scale Standard Deviation 23.6

SECONDARY outcome

Timeframe: Baseline, Cycles 1, 2, 3, 4, 5, 9, 14, End of Treatment, Follow-up Month 6, Follow-up Month 12, Follow-up Month 18

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.

Outcome measures

Outcome measures
Measure	Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane n=869 Participants 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.	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab n=891 Participants 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.
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Baseline: Arm Symptoms	19.9 Units on a Scale Standard Deviation 18.7	19.5 Units on a Scale Standard Deviation 18.4
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 1: Arm Symptoms	-1.3 Units on a Scale Standard Deviation 19.2	-3.1 Units on a Scale Standard Deviation 18.7
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 2: Arm Symptoms	-2.8 Units on a Scale Standard Deviation 18.8	-3.0 Units on a Scale Standard Deviation 18.7
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 3: Arm Symptoms	-3.5 Units on a Scale Standard Deviation 18.7	-3.5 Units on a Scale Standard Deviation 18.1
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 4: Arm Symptoms	-2.0 Units on a Scale Standard Deviation 19.8	-2.9 Units on a Scale Standard Deviation 19.2
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 5: Arm Symptoms	-0.5 Units on a Scale Standard Deviation 20.8	-2.6 Units on a Scale Standard Deviation 19.8
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 9: Arm Symptoms	-0.2 Units on a Scale Standard Deviation 20.4	-1.1 Units on a Scale Standard Deviation 19.6
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 14: Arm Symptoms	0.3 Units on a Scale Standard Deviation 21.3	1.3 Units on a Scale Standard Deviation 21.8
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at EoT: Arm Symptoms	0.1 Units on a Scale Standard Deviation 21.6	0.4 Units on a Scale Standard Deviation 21.7
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 6: Arm Symptoms	-0.1 Units on a Scale Standard Deviation 22.1	-1.3 Units on a Scale Standard Deviation 20.0
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 12: Arm Symptoms	-0.8 Units on a Scale Standard Deviation 22.4	-2.8 Units on a Scale Standard Deviation 20.5
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Baseline: Breast Symptoms	17.5 Units on a Scale Standard Deviation 17.4	16.8 Units on a Scale Standard Deviation 16.3
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 1: Breast Symptoms	-2.3 Units on a Scale Standard Deviation 16.3	-2.5 Units on a Scale Standard Deviation 16.2
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 2: Breast Symptoms	-3.3 Units on a Scale Standard Deviation 17.1	-2.9 Units on a Scale Standard Deviation 16.7
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 3: Breast Symptoms	-4.0 Units on a Scale Standard Deviation 17.5	-3.1 Units on a Scale Standard Deviation 16.5
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 4: Breast Symptoms	-3.9 Units on a Scale Standard Deviation 17.7	-3.3 Units on a Scale Standard Deviation 17.4
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 5: Breast Symptoms	-3.1 Units on a Scale Standard Deviation 18.6	-2.6 Units on a Scale Standard Deviation 18.2
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 9: Breast Symptoms	1.7 Units on a Scale Standard Deviation 19.7	0.3 Units on a Scale Standard Deviation 17.5
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 14: Breast Symptoms	-0.2 Units on a Scale Standard Deviation 18.8	0.5 Units on a Scale Standard Deviation 19.1
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at EoT: Breast Symptoms	-1.0 Units on a Scale Standard Deviation 19.3	0.3 Units on a Scale Standard Deviation 18.8
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 6: Breast Symptoms	-2.5 Units on a Scale Standard Deviation 19.1	-1.5 Units on a Scale Standard Deviation 18.4
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 12: Breast Symptoms	-4.2 Units on a Scale Standard Deviation 18.9	-3.7 Units on a Scale Standard Deviation 18.0
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Baseline: Systemic Therapy Side Effects (SE)	8.5 Units on a Scale Standard Deviation 9.9	8.7 Units on a Scale Standard Deviation 9.9
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 1: Systemic Therapy SE	24.9 Units on a Scale Standard Deviation 17.3	23.3 Units on a Scale Standard Deviation 17.6
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 2: Systemic Therapy SE	24.1 Units on a Scale Standard Deviation 18.1	18.3 Units on a Scale Standard Deviation 16.6
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 3: Systemic Therapy SE	23.4 Units on a Scale Standard Deviation 17.8	15.1 Units on a Scale Standard Deviation 15.5
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 4: Systemic Therapy SE	23.1 Units on a Scale Standard Deviation 18.1	13.2 Units on a Scale Standard Deviation 15.4
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 5: Systemic Therapy SE	20.0 Units on a Scale Standard Deviation 17.6	11.8 Units on a Scale Standard Deviation 14.7
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 9: Systemic Therapy SE	9.5 Units on a Scale Standard Deviation 13.1	10.4 Units on a Scale Standard Deviation 14.0
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 14: Systemic Therapy SE	7.5 Units on a Scale Standard Deviation 12.9	9.8 Units on a Scale Standard Deviation 13.9
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at EoT: Systemic Therapy SE	7.2 Units on a Scale Standard Deviation 13.4	8.5 Units on a Scale Standard Deviation 13.9
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 6: Systemic Therapy SE	5.8 Units on a Scale Standard Deviation 12.3	4.2 Units on a Scale Standard Deviation 12.5
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 12: Systemic Therapy SE	5.4 Units on a Scale Standard Deviation 12.9	4.2 Units on a Scale Standard Deviation 13.0
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Baseline: Upset by Hair Loss Item	13.2 Units on a Scale Standard Deviation 23.7	14.2 Units on a Scale Standard Deviation 22.9
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 1: Upset by Hair Loss Item	35.1 Units on a Scale Standard Deviation 37.3	25.2 Units on a Scale Standard Deviation 35.1
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 2: Upset by Hair Loss Item	28.7 Units on a Scale Standard Deviation 36.0	21.8 Units on a Scale Standard Deviation 36.6
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 3: Upset by Hair Loss Item	28.8 Units on a Scale Standard Deviation 36.3	21.4 Units on a Scale Standard Deviation 38.4
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 4: Upset by Hair Loss Item	28.4 Units on a Scale Standard Deviation 37.1	19.7 Units on a Scale Standard Deviation 34.2
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 5: Upset by Hair Loss Item	26.4 Units on a Scale Standard Deviation 36.8	10.0 Units on a Scale Standard Deviation 36.3
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 9: Upset by Hair Loss Item	11.8 Units on a Scale Standard Deviation 33.6	6.0 Units on a Scale Standard Deviation 36.8
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 14: Upset by Hair Loss Item	9.3 Units on a Scale Standard Deviation 32.5	2.5 Units on a Scale Standard Deviation 26.0
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at EoT: Upset by Hair Loss Item	17.3 Units on a Scale Standard Deviation 33.9	0.0 Units on a Scale Standard Deviation 28.1
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 6: Upset by Hair Loss Item	6.2 Units on a Scale Standard Deviation 26.8	-3.5 Units on a Scale Standard Deviation 21.0
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 12: Upset by Hair Loss Item	2.4 Units on a Scale Standard Deviation 28.7	-2.8 Units on a Scale Standard Deviation 29.7
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Baseline: Body Image	78.5 Units on a Scale Standard Deviation 23.2	78.9 Units on a Scale Standard Deviation 24.2
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 1: Body Image	-13.7 Units on a Scale Standard Deviation 23.5	-13.3 Units on a Scale Standard Deviation 23.1
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 2: Body Image	-12.7 Units on a Scale Standard Deviation 23.9	-10.1 Units on a Scale Standard Deviation 23.9
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 3: Body Image	-11.5 Units on a Scale Standard Deviation 24.8	-6.6 Units on a Scale Standard Deviation 22.6
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 4: Body Image	-11.4 Units on a Scale Standard Deviation 24.8	-5.9 Units on a Scale Standard Deviation 23.2
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 5: Body Image	-10.5 Units on a Scale Standard Deviation 24.6	-5.0 Units on a Scale Standard Deviation 22.6
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 9: Body Image	-5.9 Units on a Scale Standard Deviation 22.8	-4.2 Units on a Scale Standard Deviation 21.7
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 14: Body Image	-4.5 Units on a Scale Standard Deviation 23.6	-2.4 Units on a Scale Standard Deviation 23.2
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at EoT: Body Image	-3.3 Units on a Scale Standard Deviation 23.1	-2.9 Units on a Scale Standard Deviation 22.8
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 6: Body Image	-1.3 Units on a Scale Standard Deviation 23.4	0.3 Units on a Scale Standard Deviation 23.3
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 12: Body Image	0.0 Units on a Scale Standard Deviation 24.2	0.7 Units on a Scale Standard Deviation 23.5
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Baseline: Future Perspectives (FP)	49.3 Units on a Scale Standard Deviation 31.4	49.8 Units on a Scale Standard Deviation 30.9
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 1: FP	-1.3 Units on a Scale Standard Deviation 30.3	-0.3 Units on a Scale Standard Deviation 31.1
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 2: FP	1.4 Units on a Scale Standard Deviation 31.7	3.7 Units on a Scale Standard Deviation 30.4
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 3: FP	3.2 Units on a Scale Standard Deviation 32.0	6.5 Units on a Scale Standard Deviation 30.1
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 4: FP	4.2 Units on a Scale Standard Deviation 31.7	7.8 Units on a Scale Standard Deviation 30.5
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 5: FP	5.9 Units on a Scale Standard Deviation 32.4	9.7 Units on a Scale Standard Deviation 30.7
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 9: FP	8.2 Units on a Scale Standard Deviation 32.2	8.4 Units on a Scale Standard Deviation 31.3
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 14: FP	9.5 Units on a Scale Standard Deviation 32.0	7.9 Units on a Scale Standard Deviation 33.4
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at EoT: FP	8.5 Units on a Scale Standard Deviation 32.6	7.6 Units on a Scale Standard Deviation 32.3
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 6: FP	10.5 Units on a Scale Standard Deviation 31.3	12.6 Units on a Scale Standard Deviation 32.6
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 12: FP	15.0 Units on a Scale Standard Deviation 34.0	13.1 Units on a Scale Standard Deviation 33.2
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Baseline: Sexual Enjoyment	43.4 Units on a Scale Standard Deviation 32.1	46.7 Units on a Scale Standard Deviation 34.8
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 1: Sexual Enjoyment	-5.9 Units on a Scale Standard Deviation 26.8	-8.2 Units on a Scale Standard Deviation 27.0
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 2: Sexual Enjoyment	-9.5 Units on a Scale Standard Deviation 30.2	-10.7 Units on a Scale Standard Deviation 29.2
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 3: Sexual Enjoyment	-11.4 Units on a Scale Standard Deviation 26.8	-8.9 Units on a Scale Standard Deviation 31.6
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 4: Sexual Enjoyment	-11.9 Units on a Scale Standard Deviation 30.6	-9.2 Units on a Scale Standard Deviation 28.3
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 5: Sexual Enjoyment	-14.2 Units on a Scale Standard Deviation 28.1	-8.8 Units on a Scale Standard Deviation 30.4
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 9: Sexual Enjoyment	-9.4 Units on a Scale Standard Deviation 29.5	-7.4 Units on a Scale Standard Deviation 30.9
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 14: Sexual Enjoyment	-3.9 Units on a Scale Standard Deviation 28.6	-9.7 Units on a Scale Standard Deviation 31.4
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at EoT: Sexual Enjoyment	-6.5 Units on a Scale Standard Deviation 29.2	-9.7 Units on a Scale Standard Deviation 29.4
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 6: Sexual Enjoyment	-4.6 Units on a Scale Standard Deviation 28.8	-3.0 Units on a Scale Standard Deviation 30.5
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 12: Sexual Enjoyment	-5.7 Units on a Scale Standard Deviation 30.9	-2.3 Units on a Scale Standard Deviation 31.0
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Baseline: Sexual Function	16.7 Units on a Scale Standard Deviation 22.3	18.3 Units on a Scale Standard Deviation 22.9
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 1: Sexual Function	-2.3 Units on a Scale Standard Deviation 18.9	-3.5 Units on a Scale Standard Deviation 18.4
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 2: Sexual Function	-4.8 Units on a Scale Standard Deviation 19.9	-4.4 Units on a Scale Standard Deviation 18.4
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 3: Sexual Function	-5.6 Units on a Scale Standard Deviation 19.6	-3.3 Units on a Scale Standard Deviation 19.0
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 4: Sexual Function	-6.8 Units on a Scale Standard Deviation 19.7	-3.4 Units on a Scale Standard Deviation 17.9
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 5: Sexual Function	-5.9 Units on a Scale Standard Deviation 19.5	-3.0 Units on a Scale Standard Deviation 19.5
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 9: Sexual Function	-3.4 Units on a Scale Standard Deviation 19.3	-1.8 Units on a Scale Standard Deviation 20.8
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at Cycle 14: Sexual Function	-1.8 Units on a Scale Standard Deviation 20.0	-2.8 Units on a Scale Standard Deviation 20.6
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at EoT: Sexual Function	-1.5 Units on a Scale Standard Deviation 20.9	-1.7 Units on a Scale Standard Deviation 19.7
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 6: Sexual Function	1.6 Units on a Scale Standard Deviation 22.6	0.6 Units on a Scale Standard Deviation 20.4
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Change at FU Month 12: Sexual Function	0.9 Units on a Scale Standard Deviation 21.7	0.9 Units on a Scale Standard Deviation 20.9

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane n=864 Participants 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.	Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab n=884 Participants 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.
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 GHS/QoL Score	2.73 months Interval 2.1 to 2.83	13.57 months Interval 9.2 to 21.91
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 Physical Function	25.53 months Interval 13.34 to Upper limit not reached.	NA months Interval 27.43 to The median and upper limit were not reached.
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 Role Function	2.23 months Interval 2.1 to 2.79	9.92 months Interval 9.0 to 14.36
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 Cognitive Function	5.49 months Interval 2.79 to 5.82	9.46 months Interval 8.57 to 12.91

Adverse Events

Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane

Serious events: 216 serious events

Other events: 902 other events

Deaths: 45 deaths

Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab

Serious events: 195 serious events

Other events: 902 other events

Deaths: 55 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER