A Randomized Three-Arm, Multicenter Comparison of 1 Year and 2 Years of Herceptin Versus No Herceptin in Women With HER2-Positive Primary Breast Cancer Who Have Completed Adjuvant Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 5,099
- 试验地点
- 203
- 主要终点
- Percentage of Participants With Disease-Free Survival (DFS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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 (%)
排除标准
- •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
研究组 & 干预措施
Herceptin 1-Year Arm
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.
干预措施: Herceptin (Drug)
Herceptin 2-Year Arm
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.
干预措施: Herceptin (Drug)
结局指标
主要结局
Percentage of Participants With Disease-Free Survival (DFS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- 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))
- 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))
- OS Rate According to Kaplan-Meier Analysis in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up(Year 2)
- Percentage of Participants With OS Events Compared to Observation: 8-Year Median Follow-Up(From Baseline until time of event (median of 8 years))
- 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))
- DDFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up(Years 3, 5, 7, 8)
- OS Rate According to Kaplan-Meier Analysis in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up(Year 2)
- OS Rate According to Kaplan-Meier Analysis Compared to Observation: 11-Year Median Follow-Up(Years 3, 5, 7, 9, 10, 11, 12)
- 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))
- 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 Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up(Years 3, 5, 7, 8)
- 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 Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up(Years 3, 5, 7, 8)
- Percentage of Participants With OS Events Compared to Observation: 11-Year Median Follow-Up(From Baseline until time of event (median of 11 years))
- 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))
- 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)
- 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)
- 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)
- RFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up(Years 3, 5, 7, 8)
- TR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up(Years 3, 5, 7, 8)
- 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))
- 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))
- RFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up(Years 3, 5, 7, 8)
- 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))
- 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))
- 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))
- 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)
- 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))
- DTR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up(Years 3, 5, 7, 8)
- 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 Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up(Years 3, 5, 7, 8)
- 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))