HER2/Neu Positive, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer
Conditions
Brief summary
This randomized phase III trial is studying giving fluorouracil together with epirubicin and cyclophosphamide followed by paclitaxel and trastuzumab to see how well it works compared with giving paclitaxel together with trastuzumab followed by fluorouracil, epirubicin, cyclophosphamide, and trastuzumab in treating women with palpable breast cancer that can be removed by surgery. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether it is more effective to give combination chemotherapy before or after treatment with paclitaxel plus trastuzumab.
Detailed description
PRIMARY OBJECTIVES: I. The primary objective of this study is to compare the pathologic complete response rate (pCR) within the breast of a sequential regimen of concurrent weekly paclitaxel and trastuzumab, followed by continued weekly trastuzumab administered concurrently with FEC-75 (Arm 2), to the pCR rate of a sequential regimen of FEC-75 alone followed by concurrent weekly paclitaxel and trastuzumab (Arm 1). SECONDARY OBJECTIVES: I. To estimate the cardiotoxicity of a sequential regimen of concurrent weekly paclitaxel and trastuzumab, followed by continued weekly trastuzumab administered concurrently with FEC-75, followed postoperatively by q 3 week trastuzumab for a total duration of trastuzumab therapy through 52 weeks from the first dose (Arm 2), and compare the cardiotoxicity to that of a sequential regimen of FEC-75 alone followed by concurrent weekly paclitaxel and trastuzumab, followed by q 3 week trastuzumab for a total duration of trastuzumab therapy through 52 weeks from the first dose (Arm 1). II. To compare the combined pCR rate in the breast and ipsilateral axilla obtained with the two regimens evaluated in this study. III. To compare the clinical response rates (cRR) of the two regimens evaluated in this study. IV. To compare the non-cardiac toxicity of the two regimens evaluated in this study. V. To compare breast conservation rates achieved with the two regimens evaluated in this study. VI. To evaluate disease-free survival and overall survival at 5 years post-randomization. VII. To correlate pCR rate with potential molecular markers of response. OUTLINE: Patients are stratified by clinical tumor size (breast tumor size \< 2 cm and nodal metastases \< 2 cm vs breast tumor size \< 2 cm and nodal metastases ≥ 2 cm vs breast tumor size 2-4 cm \[any nodal status\] vs breast tumor size ≥ 4 cm \[any nodal status\]), age (\< 50 vs ≥ 50) and hormone receptor status (estrogen receptor \[ER\]- and progesterone receptor \[PgR\]-negative vs ER- and/or PgR-positive). Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive FEC comprising fluoroucacil intravenously (IV), epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks. ARM II: Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after completion of paclitaxel and trastuzumab, patients receive FEC comprising fluoroucacil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I. After completion of study therapy, patients are followed every 3 months for 1 year and then every 6 months for 4 years.
Interventions
DRUGCyclophosphamide
Given IV
DRUGEpirubicin Hydrochloride
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGPaclitaxel
Given IV
PROCEDURETherapeutic Conventional Surgery
Undergo surgery
BIOLOGICALTrastuzumab
Given IV
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of invasive adenocarcinoma by core needle biopsy * Fine needle aspiration allowed provided primary tumor size \< 2 cm and lymph node metastases are present * Excisional biopsy of the primary tumor allowed provided biopsy-positive lymph nodes are present * Primary tumor ≥ 2 cm and/or ≥ 1 biopsy-positive lymph node * HER2-positive disease * Confirmation by fluorescent in situ hybridization (FISH) requires gene amplification * Confirmation by immunohistochemistry (IHC) requires a strongly positive (3+) staining intensity score * Ductal carcinoma in situ (DCIS) or synchronous DCIS of the contralateral breast regardless of prior therapy allowed * Synchronous invasive breast cancer not allowed * Ipsilateral DCIS treated by local excision with or without hormonal therapy allowed * Those treated with radiation therapy are not allowed * No definitive clinical or radiologic evidence of metastatic disease * No history of invasive breast cancer * Hormone receptor status known * Menopausal status not specified * ECOG performance status of 0 -1 * Absolute neutrophil count ≥ 1,200/mm³ * Platelet count ≥ 100,000/mm³ * Total bilirubin normal unless the patient has a grade 1 bilirubin elevation (normal to 1.5 times upper limit of normal \[ULN\]) resulting from Gilbert disease or similar syndrome due to slow conjugation of bilirubin * Alkaline phosphatase ≤ 2.5 times ULN * AST ≤ 1.5 times ULN * Creatinine normal * Left ventricular ejection fraction (LVEF) ≥ 55 by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) within the past 3 months * Patients with either skeletal pain or alkaline phosphatase that is \> ULN but ≤ 2.5 times ULN allowed if bone scans fail to demonstrate metastatic disease * Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or biopsy * Prior non-breast malignancies allowed if disease-free for 5 years since completion of initial treatment regimen and deemed by their physician to be at low risk for recurrence * Patients who had the following cancers are eligible if diagnosed and treated within the past 5 years: * Carcinoma in situ of the cervix * Colon carcinoma in situ * Melanoma in situ * Basal cell and squamous cell carcinoma of the skin * No cardiac disease that would preclude the use of epirubicin hydrochloride or trastuzumab (Herceptin®) including any of the following: * Active cardiac disease * Angina pectoris that requires the use of antianginal medication * Cardiac arrhythmia requiring medication * Severe conduction abnormality * Clinically significant valvular disease * Cardiomegaly on chest x-ray * Ventricular hypertrophy on EKG * Patient's with poorly controlled hypertension ( i.e., diastolic greater than 100 mm/Hg) * Patients with hypertension that is well controlled on medication are eligible * History of cardiac disease * Myocardial infarction documented as a clinical diagnosis or by EKG or any other tests * Documented congestive heart failure * Documented cardiomyopathy * No sensory or motor neuropathy ≥ grade 2, as defined by the NCI's CTCAE v3.0 * Women of reproductive potential must agree to use an effective non-hormonal method of contraception during therapy * Women of child bearing potential must have a negative urine or serum pregnancy test within 2 weeks of registration * Not pregnant or nursing * No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements * No non-malignant systemic disease (e.g., cardiovascular, renal, hepatic) that would preclude treatment with either of the treatment regimens * No prior surgical axillary staging procedure * Prior non-excisional biopsy of an axillary node allowed * No prior treatment for this breast cancer * Hormonal therapy allowed if had been given for up to a total of 28 days anytime after diagnosis and before study entry * Hormonal therapy must stop at or before study entry and be re-started, if indicated, following surgery * No prior therapy with anthracyclines or taxanes for any malignancy * No other investigational agents within the past 30 days * No concurrent sex hormonal therapy (e.g., birth control pills, ovarian hormonal replacement therapy) * No concurrent therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulator (SERM), either for osteoporosis or breast cancer prevention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pCR Within the Breast, Defined as no Evidence of Invasive Tumor Remaining in the Breast at Surgery Following Completion of Chemotherapy | Up to 5 years | Pathological complete response (pCR) rates will be based on institutional pathology reports. In the final analysis for publication, rates will be based on blinded central review of these institutional pathology reports. The Chi-squared test will be conducted at the two-sided 0.05 level. A 95% confidence interval will be computed for the difference in pCR rates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12 | Baseline, at 12 week | The summary of asymptomatic decrease in LVEF. |
| Asymptomatic Decreases From Baseline in LVEF at Week 24 | Baseline, at 24 week | The summary of asymptomatic changed in LVEF. |
| LVEFs From Regularly Scheduled Multi Gated Acquisition Scan (MUGA)/Echo Scans as Reported at 12 Week | At 12 week | All patients who had a MUGA or ECHO performed at week 12 are included in the summary of asymptomatic changed in LVEF at week 12. Difference from pretreatment LVEF (%) at 12 weeks \[median change from baseline Inter Quartile Range (IQR)\]. |
| Combined pCR Rate in the Breast and Axillary Lymph Nodes Defined as no Evidence of Invasive Tumor Remaining in Either the Breast or Axillary Nodes at Surgery Following Completion of Chemotherapy | Up to 5 years | pCR Rate in the Breast and Axillary Lymph Nodes Defined as no Evidence of Invasive Tumor Remaining in Either the Breast or Axillary Nodes at Surgery Following Completion of Chemotherapy (among those with Metastasis to movable ipsilateral axillary lymph node(s) (cN1-3) disease). |
| Breast Conservation | From time surgery to up to 5 years | Surgery was categorized as breast conserving surgery (Partial Mastectomy) or non-conserving surgery (Total Mastectomy or Modified Radical Mastectomy). Reported below is the percentage of patients receiving Partial Mastectomy. This was calculated by dividing the number of patients receiving Partial Mastectomy by the total number of patients undergoing surgery multiplied by 100 (to obtain the percentage). |
| Disease-free Survival (DFS) | From time to registration to time of event, assessed up to 5 years | DFS defined as inoperable progressive disease, gross residual disease following definitive surgery, local, regional or distant recurrence, contralateral breast cancer, other second primary cancers, and death prior to recurrence or second primary cancer. DFS of Arm I and Arm II patients will be estimated using the Kaplan-Meier method. |
| Overall Survival (OS) | From time to registration to death, assessed up to 5 years | OS of Arm I and Arm II patients will be estimated using the Kaplan-Meier method. |
| Change in LVEFs (From Regularly Scheduled Multi Gated Acquisition Scan (MUGA)/Echo Scans) From Baseline and at 24 Week | Baseline, at 24 week | Difference from pretreatment LVEF (%) at 24 weeks \[median change from baseline Inter Quartile Range (IQR)\]. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Total Enrolled: 282, 2 patients withdrew consent before starting treatment, 280 patients started the treatment and are eligible for primary analysis.
Participants by arm
| Arm | Count |
|---|---|
| FEC-75 Then Paclitaxel/Trastuzumab Patients receive FEC comprising fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies | 138 |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies | 142 |
| Total | 280 |
Baseline characteristics
| Characteristic | FEC-75 Then Paclitaxel/Trastuzumab | Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Total |
|---|---|---|---|
| Age, Continuous | 51 years | 48 years | 50 years |
| Region of Enrollment United States | 138 participants | 142 participants | 280 participants |
| Sex: Female, Male Female | 138 Participants | 142 Participants | 280 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 136 / 138 | 141 / 142 |
| serious Total, serious adverse events | 19 / 138 | 26 / 142 |
Outcome results
Primary
pCR Within the Breast, Defined as no Evidence of Invasive Tumor Remaining in the Breast at Surgery Following Completion of Chemotherapy
Pathological complete response (pCR) rates will be based on institutional pathology reports. In the final analysis for publication, rates will be based on blinded central review of these institutional pathology reports. The Chi-squared test will be conducted at the two-sided 0.05 level. A 95% confidence interval will be computed for the difference in pCR rates.
Time frame: Up to 5 years
Population: All patients who started study treatment are included in the analysis of the primary endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FEC-75 Then Paclitaxel/Trastuzumab | pCR Within the Breast, Defined as no Evidence of Invasive Tumor Remaining in the Breast at Surgery Following Completion of Chemotherapy | 56.5 percentage of participants |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | pCR Within the Breast, Defined as no Evidence of Invasive Tumor Remaining in the Breast at Surgery Following Completion of Chemotherapy | 54.2 percentage of participants |
Comparison: The difference in pCR rates between treatment arms for pCR within the Breast, Defined as no Evidence of Invasive Tumor Remaining in the Breast at Surgery Following Completion of Chemotherapyp-value: 0.795% CI: [-9.3, 13.9]Chi-squared
Secondary
Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12
The summary of asymptomatic decrease in LVEF.
Time frame: Baseline, at 12 week
Population: All patients who had a MUGA or ECHO performed at week 12 are included in the summary of asymptomatic changed in LVEF at week 12.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FEC-75 Then Paclitaxel/Trastuzumab | Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12 | no decrease or decrease < 10%, still above LLN | 92.3 Percentage of participants |
| FEC-75 Then Paclitaxel/Trastuzumab | Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12 | decrease < 10%, below lower limit of normal (LLN) | 0.8 Percentage of participants |
| FEC-75 Then Paclitaxel/Trastuzumab | Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12 | decrease 10-15%, still above lower limit of normal | 6.2 Percentage of participants |
| FEC-75 Then Paclitaxel/Trastuzumab | Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12 | decrease 10-15%, below lower limit of normal (LLN) | 0 Percentage of participants |
| FEC-75 Then Paclitaxel/Trastuzumab | Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12 | decrease > 15%, still above lower limit of norm | 0.8 Percentage of participants |
| FEC-75 Then Paclitaxel/Trastuzumab | Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12 | decrease > 15%, below lower limit of normal | 0 Percentage of participants |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12 | decrease > 15%, still above lower limit of norm | 2.9 Percentage of participants |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12 | no decrease or decrease < 10%, still above LLN | 82.5 Percentage of participants |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12 | decrease 10-15%, below lower limit of normal (LLN) | 0 Percentage of participants |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12 | decrease < 10%, below lower limit of normal (LLN) | 0 Percentage of participants |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12 | decrease > 15%, below lower limit of normal | 2.9 Percentage of participants |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12 | decrease 10-15%, still above lower limit of normal | 11.7 Percentage of participants |
Secondary
Asymptomatic Decreases From Baseline in LVEF at Week 24
The summary of asymptomatic changed in LVEF.
Time frame: Baseline, at 24 week
Population: All patients who had a MUGA or ECHO performed at week 24 are included in the summary of asymptomatic changed in LVEF at week 24.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FEC-75 Then Paclitaxel/Trastuzumab | Asymptomatic Decreases From Baseline in LVEF at Week 24 | decrease 10-15%, below lower limit of normal (LLN) | 2.4 Percentage of Participants |
| FEC-75 Then Paclitaxel/Trastuzumab | Asymptomatic Decreases From Baseline in LVEF at Week 24 | decrease < 10%, below lower limit of normal (LLN) | 0.8 Percentage of Participants |
| FEC-75 Then Paclitaxel/Trastuzumab | Asymptomatic Decreases From Baseline in LVEF at Week 24 | decrease > 15%, still above lower limit of normal | 1.6 Percentage of Participants |
| FEC-75 Then Paclitaxel/Trastuzumab | Asymptomatic Decreases From Baseline in LVEF at Week 24 | decrease 10-15%, still above lower limit of normal | 7.9 Percentage of Participants |
| FEC-75 Then Paclitaxel/Trastuzumab | Asymptomatic Decreases From Baseline in LVEF at Week 24 | decrease > 15%, below lower limit of normal (LLN) | 4.0 Percentage of Participants |
| FEC-75 Then Paclitaxel/Trastuzumab | Asymptomatic Decreases From Baseline in LVEF at Week 24 | no decrease or decrease < 10%, still above LLN | 83.3 Percentage of Participants |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Asymptomatic Decreases From Baseline in LVEF at Week 24 | decrease > 15%, below lower limit of normal (LLN) | 0.8 Percentage of Participants |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Asymptomatic Decreases From Baseline in LVEF at Week 24 | decrease 10-15%, still above lower limit of normal | 15.4 Percentage of Participants |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Asymptomatic Decreases From Baseline in LVEF at Week 24 | decrease 10-15%, below lower limit of normal (LLN) | 0.8 Percentage of Participants |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Asymptomatic Decreases From Baseline in LVEF at Week 24 | no decrease or decrease < 10%, still above LLN | 73.1 Percentage of Participants |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Asymptomatic Decreases From Baseline in LVEF at Week 24 | decrease > 15%, still above lower limit of normal | 6.9 Percentage of Participants |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Asymptomatic Decreases From Baseline in LVEF at Week 24 | decrease < 10%, below lower limit of normal (LLN) | 3.1 Percentage of Participants |
Secondary
Breast Conservation
Surgery was categorized as breast conserving surgery (Partial Mastectomy) or non-conserving surgery (Total Mastectomy or Modified Radical Mastectomy). Reported below is the percentage of patients receiving Partial Mastectomy. This was calculated by dividing the number of patients receiving Partial Mastectomy by the total number of patients undergoing surgery multiplied by 100 (to obtain the percentage).
Time frame: From time surgery to up to 5 years
Population: All patients that underwent breast surgery were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FEC-75 Then Paclitaxel/Trastuzumab | Breast Conservation | 37.7 percentage of participants |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Breast Conservation | 39.1 percentage of participants |
Secondary
Change in LVEFs (From Regularly Scheduled Multi Gated Acquisition Scan (MUGA)/Echo Scans) From Baseline and at 24 Week
Difference from pretreatment LVEF (%) at 24 weeks \[median change from baseline Inter Quartile Range (IQR)\].
Time frame: Baseline, at 24 week
Population: All patients who had a MUGA or ECHO performed at week 24 are included in the summary of asymptomatic changed in LVEF at week 24.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FEC-75 Then Paclitaxel/Trastuzumab | Change in LVEFs (From Regularly Scheduled Multi Gated Acquisition Scan (MUGA)/Echo Scans) From Baseline and at 24 Week | -3 percent |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Change in LVEFs (From Regularly Scheduled Multi Gated Acquisition Scan (MUGA)/Echo Scans) From Baseline and at 24 Week | -4 percent |
Secondary
Combined pCR Rate in the Breast and Axillary Lymph Nodes Defined as no Evidence of Invasive Tumor Remaining in Either the Breast or Axillary Nodes at Surgery Following Completion of Chemotherapy
pCR Rate in the Breast and Axillary Lymph Nodes Defined as no Evidence of Invasive Tumor Remaining in Either the Breast or Axillary Nodes at Surgery Following Completion of Chemotherapy (among those with Metastasis to movable ipsilateral axillary lymph node(s) (cN1-3) disease).
Time frame: Up to 5 years
Population: All patients who had clinical N1-3 disease prior to the start of treatment are included in the analysis of the pCR rate in the breast and axillary lymph nodes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FEC-75 Then Paclitaxel/Trastuzumab | Combined pCR Rate in the Breast and Axillary Lymph Nodes Defined as no Evidence of Invasive Tumor Remaining in Either the Breast or Axillary Nodes at Surgery Following Completion of Chemotherapy | 48.3 Percentage (95% confidence Interval) |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Combined pCR Rate in the Breast and Axillary Lymph Nodes Defined as no Evidence of Invasive Tumor Remaining in Either the Breast or Axillary Nodes at Surgery Following Completion of Chemotherapy | 46.7 Percentage (95% confidence Interval) |
Secondary
Disease-free Survival (DFS)
DFS defined as inoperable progressive disease, gross residual disease following definitive surgery, local, regional or distant recurrence, contralateral breast cancer, other second primary cancers, and death prior to recurrence or second primary cancer. DFS of Arm I and Arm II patients will be estimated using the Kaplan-Meier method.
Time frame: From time to registration to time of event, assessed up to 5 years
Population: All patients that began protocol therapy are included in this analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FEC-75 Then Paclitaxel/Trastuzumab | Disease-free Survival (DFS) | NA months |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Disease-free Survival (DFS) | NA months |
Secondary
LVEFs From Regularly Scheduled Multi Gated Acquisition Scan (MUGA)/Echo Scans as Reported at 12 Week
All patients who had a MUGA or ECHO performed at week 12 are included in the summary of asymptomatic changed in LVEF at week 12. Difference from pretreatment LVEF (%) at 12 weeks \[median change from baseline Inter Quartile Range (IQR)\].
Time frame: At 12 week
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FEC-75 Then Paclitaxel/Trastuzumab | LVEFs From Regularly Scheduled Multi Gated Acquisition Scan (MUGA)/Echo Scans as Reported at 12 Week | 2 percent |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | LVEFs From Regularly Scheduled Multi Gated Acquisition Scan (MUGA)/Echo Scans as Reported at 12 Week | -3 percent |
Secondary
Overall Survival (OS)
OS of Arm I and Arm II patients will be estimated using the Kaplan-Meier method.
Time frame: From time to registration to death, assessed up to 5 years
Population: All patients that began protocol therapy were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FEC-75 Then Paclitaxel/Trastuzumab | Overall Survival (OS) | NA months |
| Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75 | Overall Survival (OS) | NA months |