Trial Outcomes & Findings for An Observational Follow-up Study of 1st-Line Treatment With Herceptin (Trastuzumab) in Patients With Metastatic Breast Cancer (Post-HERMINE) (NCT NCT01332981)
NCT ID: NCT01332981
Last Updated: 2016-02-22
Results Overview
The time between the first infusion of trastuzumab and the date of death from any cause. Participants who were still alive at the end of the post-HERMINE study or lost to follow-up were censored at the last date they were known to be alive.
COMPLETED
220 participants
Up to 7 years
2016-02-22
Participant Flow
This post-HERMINE study was an observational, pharmaco-epidemiological, and retrospective study. Among the 102 participants who were alive at the end of the observation period in the HERMINE study, 69 were included in the post-HERMINE study from 31 centers in France. The study was conducted between 23 February 2010 to 15 October 2010.
Overall analysis population was 220. During data check for the participants alive at the end of HERMINE study, it appeared that 1 participant was included twice. Thus, the real no. that started treatment with 1st-line trastuzumab therapy was 220 and not 221. Thus, the no. of participants still alive at the end of HERMINE study was 102 and not 103.
Participant milestones
| Measure |
Trastuzumab
Female participants with overexpression of human epidermal growth factor receptor 2 (HER2+) metastatic breast cancer treated with trastuzumab as first-line treatment since 2002, included in the pharmaco-epidemiological HERMINE study and were still alive at the end of the observation period in March 2005.
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|---|---|
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Overall Study
STARTED
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220
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Overall Study
COMPLETED
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220
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
An Observational Follow-up Study of 1st-Line Treatment With Herceptin (Trastuzumab) in Patients With Metastatic Breast Cancer (Post-HERMINE)
Baseline characteristics by cohort
| Measure |
Transtuzumab
n=220 Participants
Female participants with overexpression of human epidermal growth factor receptor 2 (HER2+) metastatic breast cancer treated with trastuzumab as first-line treatment since 2002, included in the pharmaco-epidemiological HERMINE study and were still alive at the end of the observation period in March 2005.
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|---|---|
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Age, Continuous
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55.3 Years
STANDARD_DEVIATION 12.3 • n=5 Participants
|
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Sex: Female, Male
Female
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220 Participants
n=5 Participants
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Sex: Female, Male
Male
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0 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Up to 7 yearsPopulation: Participants with HER2+ metastatic breast cancer included in HERMINE study and treated with trastuzumab as first line therapy.
The time between the first infusion of trastuzumab and the date of death from any cause. Participants who were still alive at the end of the post-HERMINE study or lost to follow-up were censored at the last date they were known to be alive.
Outcome measures
| Measure |
Transtuzumab
n=220 Participants
Female participants with overexpression of human epidermal growth factor receptor 2 (HER2+) metastatic breast cancer treated with trastuzumab as first-line treatment since 2002, included in the pharmaco-epidemiological HERMINE study and were still alive at the end of the observation period in March 2005.
|
Model 2
In the second one (Model 2), a stepwise selection was used on the significant parameters that were not correlated. The significance level for entry was 10% and the significance level for removal was 5%.
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|---|---|---|
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Median Overall Survival
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2.51 Years
Interval 2.02 to 3.02
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—
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SECONDARY outcome
Timeframe: Up to 7 yearsPopulation: Participants with HER2+ metastatic breast cancer included in HERMINE study and treated with trastuzumab as first line therapy.
The Progression-Free Survival (PFS) was defined as the time between the treatment start date (date of the first trastuzumab infusion) and the date of the first disease progression or disease-related death. Participants who had not progressed at the end of the post-HERMINE study were censored at the last date they were known to be alive. Progression-Free Survival was estimated by using Kaplan-Meier method.
Outcome measures
| Measure |
Transtuzumab
n=220 Participants
Female participants with overexpression of human epidermal growth factor receptor 2 (HER2+) metastatic breast cancer treated with trastuzumab as first-line treatment since 2002, included in the pharmaco-epidemiological HERMINE study and were still alive at the end of the observation period in March 2005.
|
Model 2
In the second one (Model 2), a stepwise selection was used on the significant parameters that were not correlated. The significance level for entry was 10% and the significance level for removal was 5%.
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|---|---|---|
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Median Time to Progression-Free Survival
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0.85 Years
Interval 0.76 to 1.03
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—
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SECONDARY outcome
Timeframe: Up to 7 yearsPopulation: Participants with HER2+ metastatic breast cancer included in HERMINE study and treated with trastuzumab as first line therapy.
The Time to Progression (TTP) was defined as the time between the treatment start date (date of the first trastuzumab infusion) and the date of the first disease progression or disease-related death. Participants who had not progressed at the end of the post-HERMINE study were censored at the last date they were known to be alive. If the cause of death was unknown, the death was considered for this analysis as due to the disease. All participants who did not progress, the death was considered to be due to the disease.
Outcome measures
| Measure |
Transtuzumab
n=220 Participants
Female participants with overexpression of human epidermal growth factor receptor 2 (HER2+) metastatic breast cancer treated with trastuzumab as first-line treatment since 2002, included in the pharmaco-epidemiological HERMINE study and were still alive at the end of the observation period in March 2005.
|
Model 2
In the second one (Model 2), a stepwise selection was used on the significant parameters that were not correlated. The significance level for entry was 10% and the significance level for removal was 5%.
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|---|---|---|
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Median Time to Progression
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0.85 Years
Interval 0.76 to 1.03
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—
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SECONDARY outcome
Timeframe: Up to 7 yearsPopulation: Participants with HER2+ metastatic breast cancer included in HERMINE study and treated with trastuzumab as first line therapy.
Treatment duration was defined as the time between the first and the last infusion of trastuzumab. Exposure duration was defined only for the participants who continued trastuzumab after HERMINE study, as the sum of treatment duration as part of HERMINE study and of the treatment durations as part of post-HERMINE study taking into account temporary treatment discontinuations. For analyses of treatment and exposure duration , dates of infusion of trastuzumab were missing for 18 participants, so treatment and exposure durations were calculated for only 202 participants.
Outcome measures
| Measure |
Transtuzumab
n=220 Participants
Female participants with overexpression of human epidermal growth factor receptor 2 (HER2+) metastatic breast cancer treated with trastuzumab as first-line treatment since 2002, included in the pharmaco-epidemiological HERMINE study and were still alive at the end of the observation period in March 2005.
|
Model 2
In the second one (Model 2), a stepwise selection was used on the significant parameters that were not correlated. The significance level for entry was 10% and the significance level for removal was 5%.
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|---|---|---|
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Median Treatment Duration and the Duration of Exposure to Trastuzumab
Total treatment duration, n=202
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1.19 Years
Interval 0.0 to 8.68
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—
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Median Treatment Duration and the Duration of Exposure to Trastuzumab
Exposure duration, n=202
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3.98 Years
Interval 1.04 to 8.06
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—
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SECONDARY outcome
Timeframe: Up to 7 yearsPopulation: Participants with HER2+ metastatic breast cancer included in HERMINE study and treated with trastuzumab as first line therapy.
Search for prognostic factors for OS was performed using Cox regression model. First, all parameters were analyzed in univariate models, and the hypothesis of proportional risks was tested. Significant parameters at 15%-level were retained for the multivariate model. For the multivariate analysis, two models were built for prognostic factors for OS. In the first one (Model 1), a stepwise selection method was used on all parameters that were significant in the univariate analyses, whatever the significance level of the associations between parameters. In the second one (Model 2), a stepwise selection was used on the significant parameters that were not correlated. The significance level for entry was 10% and the significance level for removal was 5%. The variables n°5 and n°6 were found to be significantly associated, thus only the variable n°6 was tested in the Model 2. This variable was not retained by the stepwise selection in the Model 1, contrary to the variable n°5.
Outcome measures
| Measure |
Transtuzumab
n=220 Participants
Female participants with overexpression of human epidermal growth factor receptor 2 (HER2+) metastatic breast cancer treated with trastuzumab as first-line treatment since 2002, included in the pharmaco-epidemiological HERMINE study and were still alive at the end of the observation period in March 2005.
|
Model 2
n=220 Participants
In the second one (Model 2), a stepwise selection was used on the significant parameters that were not correlated. The significance level for entry was 10% and the significance level for removal was 5%.
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|---|---|---|
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Prognostic Factors for Overall Survival
Scarff-Bloom-Richardson grade, increase >1
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1.55 Hazard Ratio
Interval 1.1 to 2.19
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1.49 Hazard Ratio
Interval 1.06 to 2.08
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Prognostic Factors for Overall Survival
Liver metastases at beginning of treatment, Yes/No
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1.60 Hazard Ratio
Interval 1.12 to 2.28
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1.55 Hazard Ratio
Interval 1.1 to 2.19
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Prognostic Factors for Overall Survival
CNS metastases at begining of treatment, Yes/No
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4.63 Hazard Ratio
Interval 2.36 to 9.09
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4.70 Hazard Ratio
Interval 2.4 to 9.2
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Prognostic Factors for Overall Survival
Time of first metastases and dose (mnths), >1 mnth
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1.04 Hazard Ratio
Interval 1.01 to 1.06
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1.04 Hazard Ratio
Interval 1.01 to 1.06
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Prognostic Factors for Overall Survival
Time:Diagnosis and 1st metastic relapse <=/>=2 Yrs
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0.52 Hazard Ratio
Interval 0.36 to 0.75
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NA Hazard Ratio
The variables n°5 and n°6 were found to be significantly associated, thus only the variable n°6 was tested in the Model 2. This variable was not retained by the stepwise selection in the Model 1, contrary to the variable n°5.
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Prognostic Factors for Overall Survival
Time:Diagnosis and 1st metastic relapse <=/>=24 m
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NA Hazard Ratio
The variables n°5 and n°6 were found to be significantly associated, thus only the variable n°6 was tested in the Model 2. This variable was not retained by the stepwise selection in the Model 1, contrary to the variable n°5.
|
0.54 Hazard Ratio
Interval 0.38 to 0.78
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SECONDARY outcome
Timeframe: Up to 7 yearsPopulation: Participants with HER2+ metastatic breast cancer included in HERMINE study and treated with trastuzumab as first line therapy.
Prognostic factors for TTP were searched by using Cox regression model. First, all parameters were analysed in univariate models, and the hypothesis of proportional risks was tested. Significant parameters at 15% level were retained for multivariate model. For multivariate analyses, 2 models were built for prognostic factor of TTP. In Model 1, stepwise selection method was used on all parameters that were significant in the univariate analyses, whatever the significance level of the associations between parameters. In Model 2, stepwise selection was used on the significant parameters that were not correlated. The significance level for entry was 10% and the significance level for exit was 5%. Six parameters remained in the Model 1 to search for prognostic factors of TTP. Once the correlated variables were removed, there were only 3 variables left in Model 2: the age was not kept by the stepwise selection. Results below are for Model 1 and similar results were obtained for Model 2
Outcome measures
| Measure |
Transtuzumab
n=220 Participants
Female participants with overexpression of human epidermal growth factor receptor 2 (HER2+) metastatic breast cancer treated with trastuzumab as first-line treatment since 2002, included in the pharmaco-epidemiological HERMINE study and were still alive at the end of the observation period in March 2005.
|
Model 2
n=220 Participants
In the second one (Model 2), a stepwise selection was used on the significant parameters that were not correlated. The significance level for entry was 10% and the significance level for removal was 5%.
|
|---|---|---|
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Prognostic Factors For Time to Progression
Age in class ≥50 years old / <50 years old
|
0.69 Hazard Ratio
Interval 0.5 to 0.94
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NA Hazard Ratio
Six parameters remained in the Model 1 to search for prognostic factors of TTP. Once the correlated variables were removed, there were only three variables left in Model 2: the age was not kept by the stepwise selection.
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|
Prognostic Factors For Time to Progression
No.of metastatic sites at trtmnt start,1/2/>2, >1
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1.34 Hazard Ratio
Interval 1.1 to 1.62
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NA Hazard Ratio
Six parameters remained in the Model 1 to search for prognostic factors of TTP. Once the correlated variables were removed, there were only three variables left in Model 2: the age was not kept by the stepwise selection.
|
|
Prognostic Factors For Time to Progression
Liver metastases at start of the treatment Yes/No
|
1.44 Hazard Ratio
Interval 1.06 to 1.94
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1.48 Hazard Ratio
Interval 1.1 to 1.98
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Prognostic Factors For Time to Progression
CNS metastases at start of the treatment Yes/No
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2.81 Hazard Ratio
Interval 1.51 to 5.22
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3.94 Hazard Ratio
Interval 2.18 to 7.1
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|
Prognostic Factors For Time to Progression
Time of first metastases and dose (mnths), >1 mnth
|
1.03 Hazard Ratio
Interval 1.01 to 1.06
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NA Hazard Ratio
Six parameters remained in the Model 1 to search for prognostic factors of TTP. Once the correlated variables were removed, there were only three variables left in Model 2: the age was not kept by the stepwise selection.
|
|
Prognostic Factors For Time to Progression
Time:Diagnosis and 1st metastic relapse <=/>=2 Yrs
|
0.64 Hazard Ratio
Interval 0.47 to 0.86
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0.68 Hazard Ratio
Interval 0.5 to 0.91
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Adverse Events
Trastuzumab
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER