Herceptin (Trastuzumab) in Treating Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Primary Breast Cancer
- Registration Number
- NCT00045032
- Lead Sponsor
- Hoffmann-La Roche
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 5099
- 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 (%)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Herceptin 1-Year Arm Herceptin Participants who have completed definitive surgery and systemic adjuvant chemotherapy will receive Herceptin for 1 year or until disease recurrence, whichever occurs first. Participants will be observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. Herceptin 2-Year Arm Herceptin Participants who have completed definitive surgery and systemic adjuvant chemotherapy will receive Herceptin for 2 years or until disease recurrence, whichever occurs first. Participants will be observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Disease-Free Survival (DFS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up From Baseline until time of event (median of 1 year) DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported. The analysis of the Herceptin 1-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed by the Sponsor in 2006 following database cleaning. The analysis of the Herceptin 2-Year Arm against the Observation Arm was performed for an Independent Data Monitoring Committee (IDMC) in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.
Percentage of Participants With DFS Events Compared to Observation: 8-Year Median Follow-Up From Baseline until time of event (median of 8 years) DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported.
DFS Rate at Year 7 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 7 DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
DFS Rate at Year 3 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 3 DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
Percentage of Participants With DFS Events Compared to Observation: 10-Year Maximum Follow-Up From Baseline until time of event (maximum of 10 years) DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported.
DFS Rate at Year 5 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up Year 5 DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.
DFS Rate According to Kaplan-Meier Analysis in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up Year 2 DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 1-year median follow-up analysis. The analysis of the Herceptin 2-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed for an IDMC in 2005 at a time the Sponsor was blinded. The analysis of the Herceptin 1-Year Arm against the Observation Arm was performed by the Sponsor in 2006 following database cleaning. Therefore, these data are reported under a separate Outcome Measure.
DFS Rate at Year 5 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 5 DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
DFS Rate at Year 3 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up Year 3 DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.
Percentage of Participants With DFS Events in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up From Baseline until time of event (median of 1 year) DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported. The analysis of the Herceptin 2-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed for an IDMC in 2005 at a time the Sponsor was blinded. The analysis of the Herceptin 1-Year Arm against the Observation Arm was performed by the Sponsor in 2006 following database cleaning. Therefore, these data are reported under a separate Outcome Measure.
DFS Rate According to Kaplan-Meier Analysis in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up Year 2 DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95 percent (%) confidence interval (CI) were estimated by Kaplan-Meier analysis based on available data at the time of the 1-year median follow-up analysis. The analysis of the Herceptin 1-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed by the Sponsor in 2006 following database cleaning. The analysis of the Herceptin 2-Year Arm against the Observation Arm was performed for an IDMC in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.
DFS Rate at Year 8 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 8 DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
DFS Rate at Year 7 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up Year 7 DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.
DFS Rate at Year 9 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up Year 9 DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.
DFS Rate at Year 10 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up Year 10 DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.
DFS Rate at Year 8 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up Year 8 DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Overall Survival (OS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up From Baseline until time of event (median of 1 year) OS events referred to death from any cause. The percentage of participants who died was reported. The analysis of the Herceptin 1-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed by the Sponsor in 2006 following database cleaning. The analysis of the Herceptin 2-Year Arm against the Observation Arm was performed for an IDMC in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.
Percentage of Participants With DFS Events in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up From Baseline until time of event (maximum of 10 years) DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported.
OS Rate According to Kaplan-Meier Analysis in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up Year 2 OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 1-year median follow-up analysis. The analysis of the Herceptin 2-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed for an IDMC in 2005 at a time the Sponsor was blinded. The analysis of the Herceptin 1-Year Arm against the Observation Arm was performed by the Sponsor in 2006 following database cleaning. Therefore, these data are reported under a separate Outcome Measure.
Percentage of Participants With OS Events Compared to Observation: 8-Year Median Follow-Up From Baseline until time of event (median of 8 years) OS events referred to death from any cause. The percentage of participants who died was reported.
Percentage of Participants With OS Events in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up From Baseline until time of event (median of 11 years) OS events referred to death from any cause. The percentage of participants who died was reported.
DDFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Years 3, 5, 7, 8 DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants free of DDFS events (i.e., the DDFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
OS Rate According to Kaplan-Meier Analysis in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up Year 2 OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 1-year median follow-up analysis. The analysis of the Herceptin 1-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed by the Sponsor in 2006 following database cleaning. The analysis of the Herceptin 2-Year Arm against the Observation Arm was performed for an IDMC in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.
OS Rate According to Kaplan-Meier Analysis Compared to Observation: 11-Year Median Follow-Up Years 3, 5, 7, 9, 10, 11, 12 OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with an 11-year median follow-up for OS events.
Percentage of Participants With RFS Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up From Baseline until time of event (median of 8 years) RFS events included local, regional, or distant tumor recurrence. The percentage of participants with at least one RFS event was reported.
Percentage of Participants With DDFS Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up From Baseline until time of event (median of 8 years) DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants with at least one DDFS event was reported.
DDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Years 3, 5, 7, 8 DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants free of DDFS events (i.e., the DDFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
Percentage of Participants With OS Events Compared to Observation: 11-Year Median Follow-Up From Baseline until time of event (median of 11 years) OS events referred to death from any cause. The percentage of participants who died was reported.
Percentage of Participants With OS Events in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up From Baseline until time of event (median of 1 year) OS events referred to death from any cause. The percentage of participants who died was reported. The analysis of the Herceptin 2-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed for an IDMC in 2005 at a time the Sponsor was blinded. The analysis of the Herceptin 1-Year Arm against the Observation Arm was performed by the Sponsor in 2006 following database cleaning. Therefore, these data are reported under a separate Outcome Measure.
OS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Years 3, 5, 7, 8 OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
Percentage of Participants With Recurrence-Free Survival (RFS) Events Compared to Observation: 8-Year Median Follow-Up From Baseline until time of event (median of 8 years) RFS events included local, regional, or distant tumor recurrence. The percentage of participants with at least one RFS event was reported.
DTR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Years 3, 5, 7, 8 The percentage of participants without DTR (i.e., the DTR-free rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.
DFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up Years 3, 5, 7, 8, 9, 10 DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.
OS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up Years 3, 5, 7, 9, 10, 11, 12 OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with an 11-year median follow-up for OS events.
RFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Years 3, 5, 7, 8 RFS events included local, regional, or distant tumor recurrence. The percentage of participants free of RFS events (i.e., the RFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
TR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Years 3, 5, 7, 8 The percentage of participants without TR of the present breast cancer (i.e., the TR-free rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.
Percentage of Participants With DTR in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up From Baseline until time of event (median of 8 years) The percentage of participants with DTR was reported. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.
Percentage of Participants With Primary Cardiac Endpoint Events Compared to Observation: 10-Year Maximum Follow-Up From Baseline until time of event (maximum up to 10 years) Primary cardiac endpoint events included the occurrence of any of the following between randomization and new therapy for recurrent disease: symptomatic New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF) confirmed by a cardiologist with a drop in left ventricular ejection fraction (LVEF) at least 10 percentage points from Baseline and to a value less than (\<) 50%, and documentation of definite or probable cardiac death. Definite cardiac death included CHF, myocardial infarction, or primary arrhythmia. Probable cardiac death included unexpected sudden death within 24 hours of a cardiac event (syncope, cardiac arrest, chest pain, infarction, arrhythmia) without documented etiology. The percentage of participants with at least one primary cardiac endpoint event was reported. The 95% CI was calculated by the Pearson-Clopper method for a one-sample binomial.
RFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Years 3, 5, 7, 8 RFS events included local, regional, or distant tumor recurrence. The percentage of participants free of RFS events (i.e., the RFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
Percentage of Participants With Distant Disease-Free Survival (DDFS) Events Compared to Observation: 8-Year Median Follow-Up From Baseline until time of event (median of 8 years) DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants with at least one DDFS event was reported.
Percentage of Participants With Tumor Recurrence (TR) Compared to Observation: 8-Year Median Follow-Up From Baseline until time of event (median of 8 years) The percentage of participants with TR of the present breast cancer was reported. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.
Percentage of Participants With TR in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up From Baseline until time of event (median of 8 years) The percentage of participants with TR of the present breast cancer was reported. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.
TR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Years 3, 5, 7, 8 The percentage of participants without TR of the present breast cancer (i.e., the TR-free rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.
Percentage of Participants With Distant Tumor Recurrence (DTR) Compared to Observation: 8-Year Median Follow-Up From Baseline until time of event (median of 8 years) The percentage of participants with DTR was reported. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.
DTR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Years 3, 5, 7, 8 The percentage of participants without DTR (i.e., the DTR-free rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.
Percentage of Participants With Restricted Disease-Free Survival (RDFS) Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up From Baseline until time of event (median of 8 years) RDFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer, or death from any cause. The percentage of participants with at least one RDFS event was reported.
RDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Years 3, 5, 7, 8 RDFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer, or death from any cause. The percentage of participants free of RDFS events (i.e., the RDFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.
Percentage of Participants With Secondary Cardiac Endpoint Events Compared to Observation: 10-Year Maximum Follow-Up From Baseline until time of event (maximum up to 10 years) Secondary cardiac endpoint events included NYHA Class I or II CHF with a drop in LVEF measured by multiple-gated acquisition or electrocardiogram, unless the subsequent assessment of LVEF indicated a return to levels that did not meet the definition of a significant LVEF drop. A significant LVEF drop was defined as an absolute reduction of at least 10 percentage points from Baseline and to a value \<50%. The percentage of participants with at least one secondary cardiac endpoint event was reported, excluding those with both a primary and secondary cardiac endpoint event. The 95% CI was calculated by the Pearson-Clopper method for a one-sample binomial.
Trial Locations
- Locations (203)
Saint John of God Hospital
🇦🇺Geelong, Australian Capital Territory, Australia
Landeskrankenhaus Klagenfurt
🇦🇹Klagenfurt, Austria
Centre Hospitalier Notre Dame - Reine Fabiola
🇧🇪Charleroi, Belgium
Andrew Love Cancer Centre
🇦🇺Geelong, Victoria, Australia
Landeskrankenhaus Feldkirch
🇦🇹Feldkirch-Tisis, Austria
Landeskrankenhaus St. Poelten
🇦🇹St. Poelten, Austria
Wilhelminenspital der Stadt Wien
🇦🇹Vienna, Austria
LKH Voecklabruck
🇦🇹Voecklabruck, Austria
Hopital Universitaire Erasme
🇧🇪Brussels, Belgium
Centre Hospitalier Universitaire de Tivoli
🇧🇪La Louviere, Belgium
Clinical Hospital Center Split
🇭🇷Split, Croatia
Innsbruck Universitaetsklinik
🇦🇹Innsbruck, Austria
Ziekenhuis Netwerk Antwerpen Middelheim
🇧🇪Antwerp, Belgium
Landeskrankenanstalten - Salzburg
🇦🇹Salzburg, Austria
Universitaetsklinik fuer Innere Medizin I
🇦🇹Vienna, Austria
A. oe. Krankenhaus Wiener Neustadt
🇦🇹Wiener Neustadt, Austria
Instituto Nacional De Cancerologia
🇨🇴Bogota, Colombia
Academisch Ziekenhuis der Vrije Universiteit Brussel
🇧🇪Brussels, Belgium
CHU Liege - Domaine Universitaire du Sart Tilman
🇧🇪Liege, Belgium
Centre Hospitalier Peltzer-La Tourelle
🇧🇪Verviers, Belgium
British Columbia Cancer Agency - Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada
Tom Baker Cancer Centre - Calgary
🇨🇦Calgary, Alberta, Canada
British Columbia Cancer Agency - Centre for the Southern Interior
🇨🇦Kelowna, British Columbia, Canada
Hospital Clinico San Borja Arriaran
🇨🇱Santiago, Chile
University Hospital of Santa Maria
🇵🇹Lisboa, Portugal
Ospedale Beata Vergine
🇨🇭Mendrisio, Switzerland
Kantonsspital - St. Gallen
🇨🇭St. Gallen, Switzerland
National Institute of Oncology
🇭🇺Budapest, Hungary
Hospital Distrital De Faro
🇵🇹Faro, Portugal
Spitaeler Chur AG
🇨🇭Chur, Switzerland
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
Ramathibodi Hospital
🇹🇭Bangkok, Thailand
Imperial College of Medicine
🇬🇧London, England, United Kingdom
Bradford Hospitals NHS Trust
🇬🇧Bradford, England, United Kingdom
James Cook University Hospital
🇬🇧Middlesbrough, England, United Kingdom
Chulalongkorn University Hospital
🇹🇭Bangkok, Thailand
Princess Royal Hospital
🇬🇧Hull, England, United Kingdom
Broomfield Hospital
🇬🇧Chelmsford, Essex, England, United Kingdom
Saint Margaret's Hospital
🇬🇧Epping Essex, England, United Kingdom
Northern Centre for Cancer Treatment at Newcastle General Hospital
🇬🇧Newcastle-Upon-Tyne, England, United Kingdom
Cancer Research Centre at Weston Park Hospital
🇬🇧Sheffield, England, United Kingdom
Southend NHS Trust Hospital
🇬🇧Westcliff-On-Sea, England, United Kingdom
Toronto East General Hospital
🇨🇦Toronto, Ontario, Canada
Azienda Ospedaliera Di Parma
🇮🇹Parma, Italy
Azienda Ospedaliera
🇮🇹Reggio Emilia, Italy
Faculdade De Medicina Do ABC
🇧🇷Santo Andre, Brazil
Hospital Santa Rita
🇧🇷Porto Alegre, Brazil
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Hospital Sao Lucas da PUCRS
🇧🇷Porto Alegre, Brazil
St. Vincent's Hospital
🇦🇹Linz Donau, Austria
LKH Villach
🇦🇹Villach, Austria
Clinique Saint-Joseph
🇧🇪Liege, Belgium
Hospital Aleman de Buenos Aires
🇦🇷Buenos Aires, Argentina
Institut Jules Bordet
🇧🇪Brussels, Belgium
Tuen Mun Hospital
🇨🇳Hong Kong, China
Margaret and Charles Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
Hospital Serruys Ziekenhuis
🇧🇪Oostende, Belgium
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Toowoomba Hospital
🇦🇺Toowoomba, Queensland, Australia
U.Z. Gasthuisberg
🇧🇪Leuven, Belgium
Clinique Sainte Elisabeth
🇧🇪Namur, Belgium
Tongji Medical University
🇨🇳Wuhan, China
Herning Central Hospital
🇩🇰Herning, Denmark
Hillerod Hospital
🇩🇰Hillerod, Denmark
Hopital du Saint-Sacrement, Quebec
🇨🇦Quebec City, Quebec, Canada
Sonderborg Sygehus
🇩🇰Sonderborg, Denmark
Fundacion Arturo Lopez Perez
🇨🇱Santiago, Chile
Hospital Militar
🇨🇱Santiago, Chile
Centralsygehus I Esbjerg
🇩🇰Esbjerg, Denmark
Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A.
🇵🇹Lisbon, Portugal
Centro Oncologico De Galicia Jose Antonio Quirogay Pineyro
🇪🇸La Coruna, Spain
Hospital de la Princesa
🇪🇸Madrid, Spain
P.A. Hertzen Research Oncology Institute
🇷🇺Moscow, Russian Federation
Johns Hopkins Singapore International Medical Centre
🇸🇬Singapore, Singapore
Universitaetsspital-Basel
🇨🇭Basel, Switzerland
Umea Universitet
🇸🇪Umea, Sweden
Hospital Cuidad de Jaen
🇪🇸Jaen, Spain
Parklands Hospital
🇿🇦Durban, South Africa
Hospital de Gran Canaria Dr. Negrin
🇪🇸Las Palmas de Gran Canaria, Spain
Medical Oncology Centre of Rosebank
🇿🇦Johannesburg, South Africa
Hospital De La Ribera
🇪🇸Alzira, Spain
Pretoria - East Hospital
🇿🇦Lynnwood, South Africa
Medical University
🇵🇱Poznan, Poland
University Hospital of Linkoping
🇸🇪Linkoping, Sweden
University Hospital of Malmoe
🇸🇪Malmo, Sweden
Consorci Hospitalari del Parc Tauli
🇪🇸Sabadell, Spain
Groote Schuur Hospital
🇿🇦Cape Town, South Africa
Complejo Hospitalario Santa Maria
🇪🇸Orense, Spain
Moscow Oncology Hospital
🇷🇺Moscow, Russian Federation
Hospital Del Mar
🇪🇸Barcelona, Spain
Hospital General Universitario Valencia
🇪🇸Valencia, Spain
Sandton Oncology Centre
🇿🇦Johannesburg, South Africa
Kantonspital Aarau
🇨🇭Aarau, Switzerland
Sahlgrenska University Hospital - Molndal at Gothenburg University
🇸🇪Molndal, Sweden
Hospital Universitario San Cecilio de Granada
🇪🇸Granada, Spain
Hospital Virgen Del La Salud
🇪🇸Toledo, Spain
Hospital Insular de Gran Canaria
🇪🇸Las Palmas, Spain
Uppsala University Hospital
🇸🇪Uppsala, Sweden
Inselspital Bern
🇨🇭Bern, Switzerland
Diana Princess of Wales Hospital
🇬🇧Grimsby, England, United Kingdom
Huddersfield Royal Infirmary
🇬🇧Huddersfield, West Yorks, England, United Kingdom
Porto Alegre Hospital
🇧🇷Porto Alegre, Rio Grande do Sul, Brazil
Ospedale Oncologico A. Businco
🇮🇹Cagliari, Italy
Ospedale Civile ASL 1
🇮🇹Sassari, Italy
Primario U.O. di Oncologia Medica
🇮🇹Trento, Italy
Ospedale Ostetrico Ginecologica Sant Anna
🇮🇹Turin, Italy
Instituto Nacional de Cancer
🇧🇷Rio de Janeiro, Brazil
Algoma Regional Cancer Program at Sault Area Hospital
🇨🇦Sault Sainte Marie, Ontario, Canada
Hospital General Universitario De Guadalajara
🇪🇸Guadalajara, Spain
Complejo Hospitalario de Pontevedra
🇪🇸Pontevedra, Spain
Hospital Universitario Nuestra Senora de la Candelaria
🇪🇸Santa Cruz de Tenerife, Spain
Complexo Hospitalario Xeral de Vigo
🇪🇸Vigo Pontevedra, Spain
Hospital Universidad Virgen Del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Mount Hospital
🇦🇺Perth, Western Australia, Australia
Reseau Hospitalier De Medecine Sociale
🇧🇪Baudour, Belgium
Cazk Groeninghe - Campus St-Niklaas
🇧🇪Kortrijk, Belgium
Fraser Valley Cancer Centre at British Columbia Cancer Agency
🇨🇦Surrey, British Columbia, Canada
Royal Victoria Hospital of Barrie
🇨🇦Barrie, Ontario, Canada
British Columbia Cancer Agency - Vancouver Island Cancer Centre
🇨🇦Victoria, British Columbia, Canada
Trillium Health Centre - Mississauga Site
🇨🇦Mississauga, Ontario, Canada
Hotel Dieu Health Sciences Hospital - Niagara
🇨🇦St. Catharines, Ontario, Canada
Windsor Regional Cancer Centre at Windsor Regional Hospital
🇨🇦Windsor, Ontario, Canada
Prince Edward Island Cancer Centre at Queen Elizabeth Hospital
🇨🇦Charlottetown, Prince Edward Island, Canada
Allan Blair Cancer Centre at Pasqua Hospital
🇨🇦Regina, Saskatchewan, Canada
Hospital Dr. Sotero Del Rio
🇨🇱Santiago, Chile
Instituto Nacional Del Cancer
🇨🇱Santiago, Chile
Queen Mary Hospital
🇨🇳Hong Kong, China
Centralsygehuset I Naestved
🇩🇰Naestved, Denmark
Centre Regional Francois Baclesse
🇫🇷Caen, France
Centre Hospital Regional Universitaire de Limoges
🇫🇷Limoges, France
Hopital Clinique Claude Bernard
🇫🇷Metz, France
Evangelisches Bethesda Krankenhaus GmbH
🇩🇪Essen, Germany
Charite - Campus Charite Mitte
🇩🇪Berlin, Germany
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Germany
Martin Luther Universitaet
🇩🇪Halle, Germany
Henriettenstiftung Krankenhaus
🇩🇪Hanover, Germany
Universitaets-Hautklinik Heidelberg
🇩🇪Heidelberg, Germany
St. Vincentius-Kliniken
🇩🇪Karlsruhe, Germany
Kreiskrankenhaus Leonberg - Frauenklinik
🇩🇪Leonberg, Germany
University Hospital Schleswig-Holstein - Kiel Campus
🇩🇪Kiel, Germany
Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
🇩🇪Magdeburg, Germany
Frauenklinik Vom Roten Kreuz
🇩🇪Munich, Germany
Klinikum Rechts Der Isar - Technische Universitaet Muenchen
🇩🇪Munich, Germany
Frauenklinik - Universitaetsklinikum Rostock am Klinikum Sudstadt
🇩🇪Rostock, Germany
Dr. Horst-Schmidt-Kliniken
🇩🇪Wiesbaden, Germany
Universitaet Ulm
🇩🇪Ulm, Germany
University of Crete School of Medicine
🇬🇷Heraklion, Crete, Greece
Evaggelismos Hospital
🇬🇷Athens, Greece
Centro Medico
🇬🇹Guatemala City, Guatemala
Hospital Roosevelt
🇬🇹Guatemala City, Guatemala
Prince of Wales Hospital
🇭🇰Shatin, New Territories, Hong Kong
Semmelweis University
🇭🇺Budapest, Hungary
Cork University Hospital
🇮🇪Cork, Ireland
Sieff Hospital
🇮🇱Safed, Israel
Fovarosi Onkormanyzat Szent Margit Korhaz, Okologia
🇭🇺Budapest, Hungary
Ospedale San Lazzaro
🇮🇹Alba, Italy
Centro di Riferimento Oncologico - Aviano
🇮🇹Aviano, Italy
Ospedale Presenti Fenaroli
🇮🇹Alzano-Lombardo, Italy
Ospedali Riuniti di Bergamo
🇮🇹Bergamo, Italy
Spedali Civili di Brescia
🇮🇹Brescia, Italy
Ospedale Bellaria
🇮🇹Bologna, Italy
Ospedale degli Infermi - ASL 12
🇮🇹Biella, Italy
Ospedale B. Ramazzini
🇮🇹Carpi, Italy
Ospedale Valduce
🇮🇹Como, Italy
Ospedale Santa Croce
🇮🇹Cuneo, Italy
Universita Degli Studi Di Florence
🇮🇹Firenze (Florence), Italy
Azienda Ospedaliero Careggi
🇮🇹Florence, Italy
Morgagni-Pierantoni Ospedale
🇮🇹Forli, Italy
Istituto Nazionale per la Ricerca sul Cancro
🇮🇹Genoa, Italy
Ospedale A. Manzoni
🇮🇹Lecco, Italy
Carlo Poma Hospital
🇮🇹Mantova, Italy
Presidio Ospedaliero
🇮🇹Livorno, Italy
European Institute of Oncology
🇮🇹Milan, Italy
University of Modena Hospital and Reggio Emilia School of Medicine
🇮🇹Modena, Italy
Ospedale Niguarda Ca'Granda
🇮🇹Milan, Italy
I.R.C.C.S. Policlinico San Matteo
🇮🇹Pavia, Italy
Policlinico Monteluce
🇮🇹Perugia, Italy
Ospedale San Filippo Neri
🇮🇹Rome, Italy
Ospedale Sant' Eugenio
🇮🇹Rome, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Tokai University School Of Medicine
🇯🇵Kanagawa, Japan
Universita di Torino
🇮🇹Turin, Italy
Academisch Ziekenhuis Maastricht
🇳🇱Maastricht, Netherlands
Tokyo Metropolitan - Komagome Hospital
🇯🇵Tokyo, Japan
Yonsei Cancer Center at Yonsei University Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Maasland Hospital
🇳🇱Sittard, Netherlands
Diakonessenhuis Utrecht
🇳🇱Utrecht, Netherlands
Medical University of Gdansk
🇵🇱Gdansk, Poland
Oncologic Center
🇵🇱Gliwice, Poland
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
🇵🇱Warsaw, Poland
Hospitais da Universidade de Coimbra (HUC)
🇵🇹Coimbra, Portugal
Instituto Portugues de Oncologia, Centro Regional de Coimbra
🇵🇹Coimbra, Portugal
Maternidade Byssaia Barreto
🇵🇹Coimbra, Portugal
Karolinska University Hospital - Huddinge
🇸🇪Stockholm, Sweden
UniversitaetsSpital Zuerich
🇨🇭Zurich, Switzerland
Cookridge Hospital at Leeds Teaching Hospital NHS Trust
🇬🇧Leeds, England, United Kingdom
Airedale General Hospital
🇬🇧West Yorkshire, England, United Kingdom
Hospital Universitario Canarias
🇪🇸La Laguna, Spain
Hospital Juan Ramon Jimenez
🇪🇸Huelva, Spain
Mount Sinai Hospital - Toronto
🇨🇦Toronto, Ontario, Canada
Saskatoon Cancer Centre at the University of Saskatchewan
🇨🇦Saskatoon, Saskatchewan, Canada