Trial Outcomes & Findings for Combination Therapy With MYOCET® (Doxorubicin HCL Liposome for Injection) in Participants With HER2-Positive Breast Cancer (NCT NCT00712881)

Last Updated: 2024-02-23

Results Overview

The pCR of breast was based upon histologic examination, as confirmed by a central panel of experts, of resected tissue .

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

126 participants

Primary outcome timeframe

At the end of Cycle 8 (each cycle length = 21 days)

Results posted on

2024-02-23

Participant Flow

Participants were randomly assigned in 1:1 ratio to investigational group (Doxorubicin \[MYOCET\] + Cyclophosphamide + Trastuzumab \[MCH\] and Docetaxel + Trastuzumab \[TH\]) and comparison group (Doxorubicin \[Anthracycline\] + Cyclophosphamide \[AC\] and Docetaxel + Trastuzumab \[TH\]).

Participant milestones

Participant milestones
Measure	Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) Participants received MCH (liposomal doxorubicin hydrochloride \[60 milligrams {mg}/square meter {m\^2}\], cyclophosphamide (600 mg/m\^2), and trastuzumab (8 or 6 mg/kilogram {kg}), administered as intravenous (IV) infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles. After 4 cycles of MCH, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[6 mg/kg\]).	Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) Participants received AC (free doxorubicin hydrochloride \[60 mg/m\^2\] and cyclophosphamide \[600 mg/m\^2\]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[8 or 6 mg/kg\]). For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles.
Overall Study STARTED	63	63
Overall Study Received at Least 1 Dose of Study Drug	62	63
Overall Study Completed 8 Cycles of Treatment	55	56
Overall Study COMPLETED	53	56
Overall Study NOT COMPLETED	10	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) Participants received MCH (liposomal doxorubicin hydrochloride \[60 milligrams {mg}/square meter {m\^2}\], cyclophosphamide (600 mg/m\^2), and trastuzumab (8 or 6 mg/kilogram {kg}), administered as intravenous (IV) infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles. After 4 cycles of MCH, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[6 mg/kg\]).	Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) Participants received AC (free doxorubicin hydrochloride \[60 mg/m\^2\] and cyclophosphamide \[600 mg/m\^2\]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[8 or 6 mg/kg\]). For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles.
Overall Study Adverse Event	3	3
Overall Study Withdrawal by Subject	1	1
Overall Study Disease Progression	2	1
Overall Study Lost to Follow-up	1	1
Overall Study Non-Compliance To Study Procedures	1	0
Overall Study Protocol Violation	1	1
Overall Study Randomized but not treated	1	0

Baseline Characteristics

Combination Therapy With MYOCET® (Doxorubicin HCL Liposome for Injection) in Participants With HER2-Positive Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received MCH (liposomal doxorubicin hydrochloride \[60 mg/m\^2\], cyclophosphamide (600 mg/m\^2), and trastuzumab (8 or 6 mg/kg), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles. After 4 cycles of MCH, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[6 mg/kg\]).	Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received AC (free doxorubicin hydrochloride \[60 mg/m\^2\] and cyclophosphamide \[600 mg/m\^2\]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[8 or 6 mg/kg\]). For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles.	Total n=126 Participants Total of all reporting groups
Age, Continuous	48.8 years STANDARD_DEVIATION 11.6 • n=5 Participants	51.1 years STANDARD_DEVIATION 11.3 • n=7 Participants	49.9 years STANDARD_DEVIATION 11.4 • n=5 Participants
Sex: Female, Male Female	63 Participants n=5 Participants	63 Participants n=7 Participants	126 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	61 Participants n=5 Participants	59 Participants n=7 Participants	120 Participants n=5 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: At the end of Cycle 8 (each cycle length = 21 days)

Population: The set of enrolled participants included all participants who were randomized to a treatment group, regardless of whether or not a participant received any study drug.

The pCR of breast was based upon histologic examination, as confirmed by a central panel of experts, of resected tissue .

Outcome measures

Outcome measures
Measure	Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received MCH (liposomal doxorubicin hydrochloride \[60 mg/m\^2\], cyclophosphamide (600 mg/m\^2), and trastuzumab (8 or 6 mg/kg), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles. After 4 cycles of MCH, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[6 mg/kg\]).	Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received AC (free doxorubicin hydrochloride \[60 mg/m\^2\] and cyclophosphamide \[600 mg/m\^2\]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[8 or 6 mg/kg\]). For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles.
Percentage of Participants Exhibiting a Pathological Complete Response (pCR) in Breast	41.3 percentage of participants	54.0 percentage of participants

SECONDARY outcome

Timeframe: At the end of Cycle 8 (each cycle length = 21 days)

Population: The set of enrolled participants included all participants who were randomized to a treatment group, regardless of whether or not a participant received any study drug.

CR: Disappearance of the lesions and no new lesions. In case of bone metastasis a CR is represented by the normalization of radiography or the complete sclerotic healing of lytic area. PR: In the case of bidimensionally measurable lesions/tumors, a decrease by at least 50% of the sum of the products of the largest perpendicular diameters of each individual lesion/tumor. In the case of unidimensionally measurable lesions a decrease by at least 50% in the largest linear tumour measurement. In the case of non-measurable but evaluable lesions an appreciable change of lesions referable to disease improvement. For bone lesions partial decrease in size or recalcification of lytic areas. No lesion should have progressed and no new lesion should appear.

Outcome measures

Outcome measures
Measure	Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received MCH (liposomal doxorubicin hydrochloride \[60 mg/m\^2\], cyclophosphamide (600 mg/m\^2), and trastuzumab (8 or 6 mg/kg), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles. After 4 cycles of MCH, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[6 mg/kg\]).	Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received AC (free doxorubicin hydrochloride \[60 mg/m\^2\] and cyclophosphamide \[600 mg/m\^2\]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[8 or 6 mg/kg\]). For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles.
Percentage of Participants Who Achieved an Objective Response (Complete Response [CR] or Partial Response [PR]), as Defined by World Health Organization (WHO) Guidelines	77.8 percentage of participants	84.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to the end of Cycle 8 (each cycle length = 21 days)

Population: The set of enrolled participants included all participants who were randomized to a treatment group, regardless of whether or not a participant received any study drug.

Occurrence of Class III or IV (NYHA) CHF has been reported. Class III: Participants with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain. Class IV: Participants with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

Outcome measures

Outcome measures
Measure	Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received MCH (liposomal doxorubicin hydrochloride \[60 mg/m\^2\], cyclophosphamide (600 mg/m\^2), and trastuzumab (8 or 6 mg/kg), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles. After 4 cycles of MCH, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[6 mg/kg\]).	Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received AC (free doxorubicin hydrochloride \[60 mg/m\^2\] and cyclophosphamide \[600 mg/m\^2\]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[8 or 6 mg/kg\]). For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles.
Percentage of Participants With Class III or IV New York Health Association (NYHA) Congestive Heart Failure (CHF)	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, up to 5 years

Population: The safety analysis set included all enrolled participants who received at least 1 dose of study drug. Here, 'Number analyzed' = participants evaluable for specified category.

The LVEF is a fraction of blood (in percent) pumped out of the left ventricle of the heart (the main pumping chamber). LVEF was measured using multigated acquisition (MUGA) or echocardiography.

Outcome measures

Outcome measures
Measure	Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) n=62 Participants Participants received MCH (liposomal doxorubicin hydrochloride \[60 mg/m\^2\], cyclophosphamide (600 mg/m\^2), and trastuzumab (8 or 6 mg/kg), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles. After 4 cycles of MCH, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[6 mg/kg\]).	Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received AC (free doxorubicin hydrochloride \[60 mg/m\^2\] and cyclophosphamide \[600 mg/m\^2\]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[8 or 6 mg/kg\]). For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Change at Cycle 4	-1.5 percentage of blood pumped out Standard Deviation 6.5	-1.0 percentage of blood pumped out Standard Deviation 5.3
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Change at Pre-surgery Visit	-0.8 percentage of blood pumped out Standard Deviation 7.1	-3.4 percentage of blood pumped out Standard Deviation 6.4
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Change at Post-surgery Visit	-1.6 percentage of blood pumped out Standard Deviation 7.3	-3.6 percentage of blood pumped out Standard Deviation 5.7
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Change at Month 12	-0.9 percentage of blood pumped out Standard Deviation 7.0	-4.4 percentage of blood pumped out Standard Deviation 8.0
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Change at Month 24	0.6 percentage of blood pumped out Standard Deviation 8.0	-4.7 percentage of blood pumped out Standard Deviation 7.9
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Change at Month 36	2.1 percentage of blood pumped out Standard Deviation 5.6	-3.8 percentage of blood pumped out Standard Deviation 7.4
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Change at Month 48	-1.3 percentage of blood pumped out Standard Deviation 8.3	-2.5 percentage of blood pumped out Standard Deviation 9.0
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Change at Month 60	-1.0 percentage of blood pumped out Standard Deviation 7.7	-1.4 percentage of blood pumped out Standard Deviation 11.0

SECONDARY outcome

Timeframe: Baseline up to the end of Cycle 8 (cycle length = 21 days)

Population: The safety analysis set included all enrolled participants who received at least 1 dose of study drug.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. The TEAE was an AE that began or worsened after treatment with study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

Outcome measures

Outcome measures
Measure	Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) n=62 Participants Participants received MCH (liposomal doxorubicin hydrochloride \[60 mg/m\^2\], cyclophosphamide (600 mg/m\^2), and trastuzumab (8 or 6 mg/kg), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles. After 4 cycles of MCH, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[6 mg/kg\]).	Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received AC (free doxorubicin hydrochloride \[60 mg/m\^2\] and cyclophosphamide \[600 mg/m\^2\]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[8 or 6 mg/kg\]). For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	62 Participants	63 Participants

SECONDARY outcome

Timeframe: Up to 5 Years after randomization

Population: The set of enrolled participants included all participants who were randomized to a treatment group, regardless of whether or not a participant received any study drug.

Progression was defined as a 25% or more increase in the size of the lesion or appearance of new lesion. If the participant did not develop an event (disease progression or death), the participant was censored at the last known tumor assessment date (or last follow-up visit without progression documented).

Outcome measures

Outcome measures
Measure	Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received MCH (liposomal doxorubicin hydrochloride \[60 mg/m\^2\], cyclophosphamide (600 mg/m\^2), and trastuzumab (8 or 6 mg/kg), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles. After 4 cycles of MCH, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[6 mg/kg\]).	Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received AC (free doxorubicin hydrochloride \[60 mg/m\^2\] and cyclophosphamide \[600 mg/m\^2\]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[8 or 6 mg/kg\]). For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles.
Percentage of Participants With Progression or Death Participants with progression or death	11.1 percentage of participants	12.7 percentage of participants
Percentage of Participants With Progression or Death Participants censored	88.9 percentage of participants	87.3 percentage of participants

SECONDARY outcome

Timeframe: At the end of Cycle 8 (each cycle length = 21 days)

Population: The set of enrolled participants included all participants who were randomized to a treatment group, regardless of whether or not a participant received any study drug.

The pCR of breast and node was based upon histologic examination, as confirmed by a central panel of experts, of breast tissue resected.

Outcome measures

Outcome measures
Measure	Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received MCH (liposomal doxorubicin hydrochloride \[60 mg/m\^2\], cyclophosphamide (600 mg/m\^2), and trastuzumab (8 or 6 mg/kg), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles. After 4 cycles of MCH, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[6 mg/kg\]).	Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received AC (free doxorubicin hydrochloride \[60 mg/m\^2\] and cyclophosphamide \[600 mg/m\^2\]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[8 or 6 mg/kg\]). For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles.
Percentage of Participants Achieving a Pathological Complete Response (pCR) in Breast and Node	38.1 percentage of participants	47.6 percentage of participants

SECONDARY outcome

Timeframe: At the end of Cycle 8 (each cycle length = 21 days)

Population: The set of enrolled participants included all participants who were randomized to a treatment group, regardless of whether or not a participant received any study drug.

Outcome measures

Outcome measures
Measure	Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received MCH (liposomal doxorubicin hydrochloride \[60 mg/m\^2\], cyclophosphamide (600 mg/m\^2), and trastuzumab (8 or 6 mg/kg), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles. After 4 cycles of MCH, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[6 mg/kg\]).	Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received AC (free doxorubicin hydrochloride \[60 mg/m\^2\] and cyclophosphamide \[600 mg/m\^2\]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[8 or 6 mg/kg\]). For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles.
Number of Participants Undergoing Breast Conservative Surgery Had breast conservative surgery	33 Participants	31 Participants
Number of Participants Undergoing Breast Conservative Surgery Missing data	7 Participants	5 Participants
Number of Participants Undergoing Breast Conservative Surgery Did not have breast conservative surgery	23 Participants	27 Participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: Safety analysis set

AEs were recorded and graded per the NCI CTCAE scale. The NCI CTCAE is a toxicity scale used to grade the severity of adverse events experienced with cancer treatment. Grade 1= Mild; Grade 2= Moderate; Grade 3= Severe; Grade 4= Life-threatening or disabling; Grade 5= Death related to AE. For summaries for the toxicity grade, participants were counted once at the greatest NCI CTCAE grade.

Outcome measures

Outcome measures
Measure	Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) n=62 Participants Participants received MCH (liposomal doxorubicin hydrochloride \[60 mg/m\^2\], cyclophosphamide (600 mg/m\^2), and trastuzumab (8 or 6 mg/kg), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles. After 4 cycles of MCH, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[6 mg/kg\]).	Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) n=63 Participants Participants received AC (free doxorubicin hydrochloride \[60 mg/m\^2\] and cyclophosphamide \[600 mg/m\^2\]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[8 or 6 mg/kg\]). For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles.
Severity of Adverse Events as Characterized by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 1	2 Participants	1 Participants
Severity of Adverse Events as Characterized by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 2	9 Participants	12 Participants
Severity of Adverse Events as Characterized by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 3	19 Participants	18 Participants
Severity of Adverse Events as Characterized by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 4	32 Participants	32 Participants
Severity of Adverse Events as Characterized by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 5	0 Participants	0 Participants

Adverse Events

Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH)

Serious events: 18 serious events

Other events: 62 other events

Deaths: 0 deaths

Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH)

Serious events: 21 serious events

Other events: 63 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products R&D, Inc.

Phone: 1-888-483-8279

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Publication restrictions are in place

Restriction type: OTHER

Measure	Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) n=62 participants at risk Participants received MCH (liposomal doxorubicin hydrochloride \[60 mg/m\^2\], cyclophosphamide (600 mg/m\^2), and trastuzumab (8 or 6 mg/kg), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles. After 4 cycles of MCH, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[6 mg/kg\]).	Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) n=63 participants at risk Participants received AC (free doxorubicin hydrochloride \[60 mg/m\^2\] and cyclophosphamide \[600 mg/m\^2\]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment changed to 4 consecutive 21-day cycles of TH (docetaxel \[100 mg/m\^2\] and trastuzumab \[8 or 6 mg/kg\]). For the first cycle, the loading dose of trastuzumab was 8 mg/kg; 6 mg/kg was used for the remaining cycles.
Blood and lymphatic system disorders Febrile neutropenia	14.5% 9/62 • Number of events 9 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	11.1% 7/63 • Number of events 7 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Leukopenia	1.6% 1/62 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/63 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Cardiac disorders Atrial fibrillation	0.00% 0/62 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	1.6% 1/63 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Cardiac disorders Cyanosis	1.6% 1/62 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/63 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Cardiac disorders Myocardial infarction	0.00% 0/62 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	1.6% 1/63 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Vertigo positional	1.6% 1/62 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/63 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/62 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	1.6% 1/63 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/62 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	3.2% 2/63 • Number of events 2 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
General disorders Asthenia	1.6% 1/62 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/63 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
General disorders Fatigue	1.6% 1/62 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/63 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
General disorders Pyrexia	1.6% 1/62 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	3.2% 2/63 • Number of events 2 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Catheter related infection	0.00% 0/62 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	1.6% 1/63 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Device related infection	0.00% 0/62 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	1.6% 1/63 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Erysipelas	1.6% 1/62 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/63 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	0.00% 0/62 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	1.6% 1/63 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	1.6% 1/62 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/63 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Infections and infestations Wound infection	0.00% 0/62 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	1.6% 1/63 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Whiplash injury	0.00% 0/62 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	1.6% 1/63 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Acute polyneuropathy	1.6% 1/62 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/63 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness	1.6% 1/62 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/63 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.6% 1/62 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/63 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/62 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	1.6% 1/63 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Vascular disorders Aneurysm	1.6% 1/62 • Number of events 2 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/63 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Vascular disorders Capillary leak syndrome	0.00% 0/62 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	1.6% 1/63 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Vascular disorders Deep vein thrombosis	1.6% 1/62 • Number of events 1 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.	0.00% 0/63 • Up to 5 years after randomization The safety analysis set included all enrolled participants who received at least 1 dose of study drug.