Phase 3
Completed N=5,099
Herceptin (Trastuzumab) in Treating Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Primary Breast Cancer
Source: ClinicalTrials.gov NCT00045032 ↗Enrolled (actual)
5,099
Serious AEs
14.8%
Results posted
Apr 2017
Primary outcomePrimary: Percentage of Participants With Disease-Free Survival (DFS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up — 12.9; 7.5 percentage of participants — p=<0.0001
◆ Published Evidence
Highly cited
1,513citations · ~80 / year
2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial.
Summary
The purpose of this trial is to evaluate Herceptin treatment for 1 year and 2 years (versus observation/no Herceptin) in women with HER2-overexpressing primary breast cancer who have completed (neo-)adjuvant systemic chemotherapy, definitive surgery, and radiotherapy, if applicable. Efficacy and safety will be assessed for 10 years from randomization for each participant. All participants will continue to be followed for survival until 10 years after enrollment of the last participant.
Linked Publications (5)
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2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial.
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Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial.
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Longer-term assessment of trastuzumab-related cardiac adverse events in the Herceptin Adjuvant (HERA) trial.
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Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial.
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Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Disease-Free Survival (DFS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up |
12.9; 7.5 | <0.0001 sig |
| PRIMARY Percentage of Participants With DFS Events in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up |
13.0; 7.6 | 0.000 sig |
| PRIMARY DFS Rate According to Kaplan-Meier Analysis in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up |
78.18; 85.80 | — |
| PRIMARY DFS Rate According to Kaplan-Meier Analysis in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up |
73.60; 87.50 | — |
| PRIMARY Percentage of Participants With DFS Events Compared to Observation: 8-Year Median Follow-Up |
33.6; 27.7; 27.8 | <0.0001 sig |
| PRIMARY DFS Rate at Year 3 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up |
75.2; 81.3; 83.5 | — |
| PRIMARY DFS Rate at Year 5 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up |
70.0; 75.9; 76.5 | — |
| PRIMARY DFS Rate at Year 7 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up |
66.0; 72.4; 72.5 | — |
| PRIMARY DFS Rate at Year 8 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up |
64.8; 71.2; 71.0 | — |
| PRIMARY Percentage of Participants With DFS Events Compared to Observation: 10-Year Maximum Follow-Up |
35.8; 29.7; 30.5 | — |
| PRIMARY DFS Rate at Year 3 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up |
75.2; 81.3; 83.4 | — |
| PRIMARY DFS Rate at Year 5 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up |
70.0; 75.9; 76.4 | — |
| PRIMARY DFS Rate at Year 7 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up |
65.8; 72.4; 72.5 | — |
| PRIMARY DFS Rate at Year 8 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up |
64.7; 71.2; 70.7 | — |
| PRIMARY DFS Rate at Year 9 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up |
63.5; 70.3; 69.2 | — |
| PRIMARY DFS Rate at Year 10 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up |
62.5; 69.3; 68.5 | — |
| SECONDARY Percentage of Participants With DFS Events in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up |
25.8; 26.6 | 0.7962 |
| SECONDARY DFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up |
86.7; 89.0; 81.0; 81.6; 77.2; 77.4 | — |
| SECONDARY Percentage of Participants With Overall Survival (OS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up |
2.4; 1.8 | 0.2379 |
| SECONDARY Percentage of Participants With OS Events in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up |
2.2; 1.4 | 0.003 sig |
| SECONDARY OS Rate According to Kaplan-Meier Analysis in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up |
94.98; 95.88 | — |
| SECONDARY OS Rate According to Kaplan-Meier Analysis in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up |
94.39; 97.28 | — |
| SECONDARY Percentage of Participants With OS Events Compared to Observation: 8-Year Median Follow-Up |
20.6; 16.3; 16.1 | 0.0005 sig |
| SECONDARY OS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up |
90.7; 92.7; 94.4; 84.5; 86.9; 88.7 | — |
| SECONDARY Percentage of Participants With OS Events Compared to Observation: 11-Year Median Follow-Up |
23.9; 18.8; 18.4 | — |
| SECONDARY OS Rate According to Kaplan-Meier Analysis Compared to Observation: 11-Year Median Follow-Up |
90.7; 92.7; 94.4; 84.5; 86.9; 88.7 | — |
| SECONDARY Percentage of Participants With OS Events in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up |
14.7; 14.9 | 0.9156 |
| SECONDARY OS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up |
96.5; 97.4; 91.4; 92.6; 88.6; 88.7 | — |
| SECONDARY Percentage of Participants With Recurrence-Free Survival (RFS) Events Compared to Observation: 8-Year Median Follow-Up |
29.8; 23.4; 22.6 | <0.0001 sig |
| SECONDARY RFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up |
76.4; 82.7; 86.0; 71.9; 78.4; 79.9 | — |
| SECONDARY Percentage of Participants With RFS Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up |
19.7; 18.8 | 0.4755 |
| SECONDARY RFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up |
87.7; 90.9; 83.1; 84.5; 80.2; 81.3 | — |
| SECONDARY Percentage of Participants With Distant Disease-Free Survival (DDFS) Events Compared to Observation: 8-Year Median Follow-Up |
28.8; 23.4; 23.2 | <0.0001 sig |
| SECONDARY DDFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up |
78.6; 84.4; 85.9; 74.2; 79.6; 80.2 | — |
| SECONDARY Percentage of Participants With DDFS Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up |
19.5; 19.5 | 0.9626 |
| SECONDARY DDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up |
89.4; 90.8; 84.5; 84.7; 81.4; 81.1 | — |
| SECONDARY Percentage of Participants With Tumor Recurrence (TR) Compared to Observation: 8-Year Median Follow-Up |
29.8; 23.4; 22.6 | <0.0001 sig |
| SECONDARY TR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up |
76.5; 82.8; 86.1; 72.1; 78.6; 80.1 | — |
| SECONDARY Percentage of Participants With TR in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up |
19.7; 18.8 | 0.4500 |
| SECONDARY TR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up |
87.7; 90.9; 83.2; 84.7; 80.4; 81.5 | — |
| SECONDARY Percentage of Participants With Distant Tumor Recurrence (DTR) Compared to Observation: 8-Year Median Follow-Up |
25.3; 19.4; 18.8 | <0.0001 sig |
| SECONDARY DTR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up |
79.8; 85.9; 88.1; 76.5; 82.1; 83.4 | — |
| SECONDARY Percentage of Participants With DTR in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up |
15.5; 15.1 | 0.6823 |
| SECONDARY DTR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up |
90.5; 92.4; 86.7; 87.5; 84.6; 84.9 | — |
| SECONDARY Percentage of Participants With Restricted Disease-Free Survival (RDFS) Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up |
22.2; 21.9 | 0.7251 |
| SECONDARY RDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up |
87.3; 89.9; 81.9; 83.0; 78.5; 78.9 | — |
| SECONDARY Percentage of Participants With Primary Cardiac Endpoint Events Compared to Observation: 10-Year Maximum Follow-Up |
0.11; 1.07; 1.02 | — |
| SECONDARY Percentage of Participants With Secondary Cardiac Endpoint Events Compared to Observation: 10-Year Maximum Follow-Up |
0.86; 4.40; 7.29 | — |
Eligibility Criteria
Inclusion Criteria
- Non-metastatic primary invasive breast cancer overexpressing HER2 (determined by immunohistochemistry 3+ or positive fluorescence in situ hybridization test) that has been histologically confirmed, adequately excised, axillary node positive or negative, and tumor size at least T1c according to Tumor/Node/Metastasis (TNM) staging
- Completion of at least 4 cycles of (neo-)adjuvant systemic chemotherapy, definitive surgery, and radiotherapy, if applicable
- Known hormone receptor status
- Baseline left ventricular ejection fraction (LVEF) greater than or equal to (≥) 55 percent (%)
Exclusion Criteria
- Prior invasive breast carcinoma
- Other malignancies except for curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix
- Clinical T4 tumors
- Cumulative doxorubicin exposure greater than (>) 360 milligrams per meter-squared (mg/m^2) or epirubicin >720 mg/m^2 or any prior anthracyclines unrelated to the present breast cancer
- Peripheral stem cell or bone marrow stem cell support
- Prior mediastinal irradiation except for internal mammary node irradiation for the present breast cancer
- Non-irradiated internal mammary nodes or supraclavicular lymph node involvement
- Prior anti-HER2 therapy for any other reason or other prior biologic or immunotherapy for breast cancer
- Concurrent anti-cancer treatment in another investigational trial
- Serious cardiac or pulmonary conditions/illness, or any other conditions that could interfere with planned treatment
- Poor hematologic, hepatic, or renal function
- Pregnancy or lactation
- Women of childbearing potential or less than 1 year post-menopause unwilling to use adequate contraceptive measures
Data sourced from ClinicalTrials.gov (NCT00045032) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.