Breast Cancer
Conditions
Brief summary
This 2 arm study will compare the efficacy and safety of continuation or discontinuation of Herceptin treatment in combination with 2nd line chemotherapy, in patients with HER2 positive metastatic breast cancer whose condition has progressed on 1st line chemotherapy plus Herceptin. Patients will be randomized either to continue or discontinue Herceptin treatment (6mg/kg iv infusion every 3 weeks) while receiving second-line chemotherapy of the investigator's choice. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.
Interventions
As prescribed
6mg/kg iv every 3 weeks
Sponsors
Hoffmann-La Roche
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
* female patients, \>= 18 years of age; * metastatic breast cancer; * HER2 overexpression (IHC 3+ and/or FISH positive); * disease progression during or after previous 1st line chemotherapy + Herceptin; * scheduled to receive 2nd line chemotherapy.
Exclusion criteria
* concurrent immunotherapy or hormonal therapy; * anthracyclines as part of previous 1st line chemotherapy or planned 2nd line chemotherapy; * cardiac toxicity during previous 1st line chemotherapy + Herceptin; * history of other malignancy within last 5 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Time to Disease Progression | Up to 5 years | Time to disease progression (TTP) in days was defined as the time from enrollment to objective disease progression (all categories other than objective disease progression was set to be censored including death before progression). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions. Tumor assessments were performed using computer tomography or magnetic resonance imaging. TTP as assessed by investigator, along with a recalculation done by computer algorithm is presented below. Median time was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hematology Safety Laboratory Parameter: Mean Platelets Counts | Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years) | Participants in the study were evaluated for the platelets at Visit 1 and final study assessments. Platelet counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice. |
| Clinical Benefit Rate | Up to 5 years | Clinical benefit rate (CBR) was defined as the percentage of participants taking a benefit from the treatments. CBR includes 1) Complete response (CR): disappearance of all target lesions and all non-target non-measurable lesions 2) Partial response (PR) : \>=30% decrease in the sum of the longest diameter of target lesions and 3) Stable disease (SD): non-PR and non-progressive disease. It was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and assessed by CT or MRI by the investigator. CBR was also assessed by computer. Clinical benefit rate was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice. |
| Median Time to Treatment Failure | Up to 5 years | Time to treatment failure is defined as a composite endpoint measuring time (number of days) from enrollment to discontinuation of treatment or change in treatment for any reason, including disease progression, treatment toxicity and death. Median time to treatment failure was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice. |
| Overall Survival | Up to 5 years | Overall Survival is defined as the time (number of days) between enrollment and the date of death due to any cause. Overall survival was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice. |
| Number of Participants With Any Adverse Events and Serious Adverse Events | Up to 5 years | An adverse event (AE) is any untoward medical occurrence in a participant who is administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. |
| Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels | Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study Assessments (Up to 5 years) | Participants in the study were evaluated for the serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkali phosphatase (ALP) at Visit 1 and final study assessments (Up to 5 years). Serum glutamic oxaloacetic transaminase, Serum glutamic-pyruvic transaminase and Alkali Phosphatase levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice. |
| Objective Response Rate | Up to 5 years | Objective response rate (ORR) is defined as the percentage of participants with tumor shrinkage of a predefined amount. It is a combination of complete response (CR) and partial response (PR) and was assessed according to the RECIST criteria 1.0. Complete response refers to the disappearance of all target lesions and all non-target non-measurable lesions. Partial Response refers to an at least 30 percent decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter. Objective response rate was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice. |
| Biochemistry Safety Laboratory Parameters: Mean Albumin Levels | Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study assessments (Up to 5 years) | Participants in the study were evaluated for the albumin at Visit 1 and Final study assessments. Albumin levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice. |
| Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels | Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study assessments (Up to 5 years) | Participants in the study were evaluated for the biochemical safety laboratory parameters urea, sodium and potassium. Urea, sodium and potassium levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice. |
| Hematology Safety Laboratory Parameters: Mean Hemoglobin Levels | Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years) | Participants in the study were evaluated for the Hemoglobin up to 5 years. Hemoglobin levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice. |
| Hematology Safety Laboratory Parameters: Mean Total Leukocytes Counts | Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years) | Participants in the study were evaluated for the total leukocytes up to 5 years. Total leukocytes counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice. |
| Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts | Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years) | Participants in the study were evaluated for the Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes at Visit 1 and final study assessments. Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice. |
| Mean Left Ventricular Ejection Fraction | Visit 0 [Screening period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years). | Left ventricular ejection fraction (LVEF) is a measure of the percent of blood ejected from the ventricle in one heartbeat. It is a measure of cardiac function and was assessed by echocardiogram or multigated angiogram at Visit 0 \[Screening period (6 weeks prior to enrollment)\] and final study assessments (Up to 5 years). |
| Biochemistry Safety Laboratory Parameters: Mean Total Bilirubin and Serum Creatinine Levels | Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study Assessments (Up to 5 years) | Participants in the study were evaluated for the total bilirubin and serum creatinine. Total Bilirubin and serum creatinine levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice. |
Countries
Bulgaria, Estonia, Hungary, Israel, Lithuania, North Macedonia, Slovakia, Turkey (Türkiye)
Participant flow
Recruitment details
A total of 114 participants were enrolled in this study conducted from March 2007 to August 2011 at 30 centers in 8 countries.
Pre-assignment details
Of 114 participants screened, 3 participants were screening failures. The reasons for screening failure were violation of inclusion criteria, refused to take part in the study and bacterial infection. Therefore, 111 participants were randomized to receive study treatment. Two participants were randomized but never started study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab + 2nd Line Chemotherapy Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy. | 93 |
| Only Chemotherapy Eligible participants were administered second line chemotherapy according to the investigator's decision. | 16 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 1 |
| Overall Study | Investigator decision | 3 | 0 |
| Overall Study | Missing | 0 | 5 |
| Overall Study | Progression of the disease | 73 | 8 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Refused treatment/did not cooperate | 4 | 1 |
Baseline characteristics
| Characteristic | Trastuzumab + 2nd Line Chemotherapy | Only Chemotherapy | Total |
|---|---|---|---|
| Age, Continuous | 55.4 years STANDARD_DEVIATION 12.8 | 56.3 years STANDARD_DEVIATION 10.2 | 55.5 years STANDARD_DEVIATION 12.4 |
| Sex: Female, Male Female | 93 Participants | 16 Participants | 109 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 | 81 / 93 | 9 / 16 |
| serious Total, serious adverse events | 20 / 93 | 2 / 16 |
Outcome results
Primary
Median Time to Disease Progression
Time to disease progression (TTP) in days was defined as the time from enrollment to objective disease progression (all categories other than objective disease progression was set to be censored including death before progression). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions. Tumor assessments were performed using computer tomography or magnetic resonance imaging. TTP as assessed by investigator, along with a recalculation done by computer algorithm is presented below. Median time was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Time frame: Up to 5 years
Population: The Full-Analysis-Set included all participants who were enrolled and had at least one valid primary efficacy variable on active treatment. n = Numbers of participants included in this analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Median Time to Disease Progression | By Computer (n = 65) | 171 Days |
| Trastuzumab + 2nd Line Chemotherapy | Median Time to Disease Progression | By Investigator (n = 73) | 171 Days |
Secondary
Biochemistry Safety Laboratory Parameters: Mean Albumin Levels
Participants in the study were evaluated for the albumin at Visit 1 and Final study assessments. Albumin levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study assessments (Up to 5 years)
Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Albumin Levels | Albumin, Visit 1, (n = 84) | 43.99 gram per liter | Standard Deviation 3.29 |
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Albumin Levels | Albumin, Final study assessments, (n = 54) | 41.07 gram per liter | Standard Deviation 6.96 |
Secondary
Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels
Participants in the study were evaluated for the serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkali phosphatase (ALP) at Visit 1 and final study assessments (Up to 5 years). Serum glutamic oxaloacetic transaminase, Serum glutamic-pyruvic transaminase and Alkali Phosphatase levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study Assessments (Up to 5 years)
Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels | SGOT, Visit 1, (n = 93) | 31.46 Units per liter | Standard Deviation 29.78 |
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels | SGOT, Final study assessments, (n = 62) | 36.16 Units per liter | Standard Deviation 34.91 |
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels | SGPT, Visit 1, (n = 93) | 25.86 Units per liter | Standard Deviation 20.55 |
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels | SGPT, Final study assessments, (n = 61) | 28.19 Units per liter | Standard Deviation 16.92 |
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels | ALP, Visit 1, (n = 93) | 202.30 Units per liter | Standard Deviation 149.98 |
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels | ALP, Final study assessments, (n = 62) | 193.49 Units per liter | Standard Deviation 148.11 |
Secondary
Biochemistry Safety Laboratory Parameters: Mean Total Bilirubin and Serum Creatinine Levels
Participants in the study were evaluated for the total bilirubin and serum creatinine. Total Bilirubin and serum creatinine levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study Assessments (Up to 5 years)
Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Total Bilirubin and Serum Creatinine Levels | Total bilirubin, Visit 1, (n = 93) | 13.50 Micromole/liter | Standard Deviation 42.74 |
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Total Bilirubin and Serum Creatinine Levels | Total bilirubin, Final study assessments(n = 60) | 19.16 Micromole/liter | Standard Deviation 36.77 |
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Total Bilirubin and Serum Creatinine Levels | Serum creatinine, Visit 1, (n = 92) | 81.18 Micromole/liter | Standard Deviation 61.75 |
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Total Bilirubin and Serum Creatinine Levels | Serum creatinine,Final study assessment (n = 63) | 82.53 Micromole/liter | Standard Deviation 70.86 |
Secondary
Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels
Participants in the study were evaluated for the biochemical safety laboratory parameters urea, sodium and potassium. Urea, sodium and potassium levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study assessments (Up to 5 years)
Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels | Urea, Visit 1, (n = 92) | 6.33 Millimole per liter | Standard Deviation 3.07 |
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels | Urea, Final study assessments, (n = 63) | 6.92 Millimole per liter | Standard Deviation 4.93 |
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels | Sodium, Visit 1, (n = 92) | 140.58 Millimole per liter | Standard Deviation 3.34 |
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels | Sodium, Final study assessments, (n = 61) | 139.16 Millimole per liter | Standard Deviation 3.71 |
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels | Potassium, Visit 1, (n = 91) | 4.40 Millimole per liter | Standard Deviation 0.45 |
| Trastuzumab + 2nd Line Chemotherapy | Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels | Potassium, Final study assessments, (n = 61) | 4.22 Millimole per liter | Standard Deviation 0.4 |
Secondary
Clinical Benefit Rate
Clinical benefit rate (CBR) was defined as the percentage of participants taking a benefit from the treatments. CBR includes 1) Complete response (CR): disappearance of all target lesions and all non-target non-measurable lesions 2) Partial response (PR) : \>=30% decrease in the sum of the longest diameter of target lesions and 3) Stable disease (SD): non-PR and non-progressive disease. It was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and assessed by CT or MRI by the investigator. CBR was also assessed by computer. Clinical benefit rate was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Time frame: Up to 5 years
Population: The Full-Analysis-Set participants with measurable disease with CR, PR and SD. Study design was changed to single arm study because herceptin use after progression herceptin-based therapy become widespread.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Clinical Benefit Rate | By Computer (n = 87) | 75.9 Percentage of participants |
| Trastuzumab + 2nd Line Chemotherapy | Clinical Benefit Rate | By Investigator (n = 87) | 72.4 Percentage of participants |
Secondary
Hematology Safety Laboratory Parameter: Mean Platelets Counts
Participants in the study were evaluated for the platelets at Visit 1 and final study assessments. Platelet counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)
Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameter: Mean Platelets Counts | Platelets, Visit 1, (n = 93) | 263.14 Number of cells x 10^9/L | Standard Deviation 63.91 |
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameter: Mean Platelets Counts | Platelets, Final study assessments, (n = 67) | 256.64 Number of cells x 10^9/L | Standard Deviation 78.64 |
Secondary
Hematology Safety Laboratory Parameters: Mean Hemoglobin Levels
Participants in the study were evaluated for the Hemoglobin up to 5 years. Hemoglobin levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)
Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameters: Mean Hemoglobin Levels | Hemoglobin, Visit 1, (n = 93) | 12.67 grams per deciliter | Standard Deviation 2.03 |
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameters: Mean Hemoglobin Levels | Hemoglobin, Final study assessments, (n = 67) | 11.00 grams per deciliter | Standard Deviation 3.57 |
Secondary
Hematology Safety Laboratory Parameters: Mean Total Leukocytes Counts
Participants in the study were evaluated for the total leukocytes up to 5 years. Total leukocytes counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)
Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameters: Mean Total Leukocytes Counts | Total Leukocytes, Visit 1, (n = 92) | 8.00 10^9 leukocytes/L | Standard Deviation 8.6 |
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameters: Mean Total Leukocytes Counts | Total Leukocytes, Final study assessment (n =67) | 7.53 10^9 leukocytes/L | Standard Deviation 6.88 |
Secondary
Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts
Participants in the study were evaluated for the Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes at Visit 1 and final study assessments. Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Time frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)
Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts | Neutrophils, Visit 1, (n = 93) | 64.89 percent of differential | Standard Deviation 10.66 |
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts | Neutrophils, Final study assessments, (n = 64) | 62.22 percent of differential | Standard Deviation 14.8 |
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts | Basophils, Visit 1, (n = 86) | 0.38 percent of differential | Standard Deviation 0.33 |
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts | Basophils, Final study assessments, (n = 59) | 1.28 percent of differential | Standard Deviation 6.34 |
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts | Eosinophils, Visit 1, (n = 88) | 2.36 percent of differential | Standard Deviation 2.15 |
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts | Eosinophils, Final study assessments, (n = 61) | 2.50 percent of differential | Standard Deviation 3.56 |
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts | Lymphocytes, Visit 1, (n = 93) | 26.34 percent of differential | Standard Deviation 9.37 |
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts | Lymphocytes, Final study assessments, (n = 64) | 26.48 percent of differential | Standard Deviation 12.85 |
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts | Monocytes, Visit 1, (n = 89) | 5.92 percent of differential | Standard Deviation 2.22 |
| Trastuzumab + 2nd Line Chemotherapy | Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts | Monocytes, Final study assessments, (n = 59) | 7.25 percent of differential | Standard Deviation 3.56 |
Secondary
Mean Left Ventricular Ejection Fraction
Left ventricular ejection fraction (LVEF) is a measure of the percent of blood ejected from the ventricle in one heartbeat. It is a measure of cardiac function and was assessed by echocardiogram or multigated angiogram at Visit 0 \[Screening period (6 weeks prior to enrollment)\] and final study assessments (Up to 5 years).
Time frame: Visit 0 [Screening period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years).
Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Mean Left Ventricular Ejection Fraction | Visit 0 (n = 92, 16) | 63.3 percent of blood pumped from LV chamber] | Standard Deviation 6.8 |
| Trastuzumab + 2nd Line Chemotherapy | Mean Left Ventricular Ejection Fraction | Final study assessment (n= 53, 5) | 61.2 percent of blood pumped from LV chamber] | Standard Deviation 7.4 |
| Only Chemotherapy | Mean Left Ventricular Ejection Fraction | Visit 0 (n = 92, 16) | 62.6 percent of blood pumped from LV chamber] | Standard Deviation 6.9 |
| Only Chemotherapy | Mean Left Ventricular Ejection Fraction | Final study assessment (n= 53, 5) | 68.6 percent of blood pumped from LV chamber] | Standard Deviation 5.9 |
Secondary
Median Time to Treatment Failure
Time to treatment failure is defined as a composite endpoint measuring time (number of days) from enrollment to discontinuation of treatment or change in treatment for any reason, including disease progression, treatment toxicity and death. Median time to treatment failure was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Time frame: Up to 5 years
Population: The Full-Analysis-Set included all participants who were enrolled and had at least one valid primary efficacy variable on active treatment. Only those participants who experienced treatment failure were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Median Time to Treatment Failure | 154 Days |
Secondary
Number of Participants With Any Adverse Events and Serious Adverse Events
An adverse event (AE) is any untoward medical occurrence in a participant who is administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.
Time frame: Up to 5 years
Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Number of Participants With Any Adverse Events and Serious Adverse Events | Number of participants with any AE | 84 Number of participants |
| Trastuzumab + 2nd Line Chemotherapy | Number of Participants With Any Adverse Events and Serious Adverse Events | Number of participants with any SAE | 20 Number of participants |
| Only Chemotherapy | Number of Participants With Any Adverse Events and Serious Adverse Events | Number of participants with any AE | 10 Number of participants |
| Only Chemotherapy | Number of Participants With Any Adverse Events and Serious Adverse Events | Number of participants with any SAE | 2 Number of participants |
Secondary
Objective Response Rate
Objective response rate (ORR) is defined as the percentage of participants with tumor shrinkage of a predefined amount. It is a combination of complete response (CR) and partial response (PR) and was assessed according to the RECIST criteria 1.0. Complete response refers to the disappearance of all target lesions and all non-target non-measurable lesions. Partial Response refers to an at least 30 percent decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter. Objective response rate was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Time frame: Up to 5 years
Population: The Full-Analysis-Set participants with measurable disease with CR or PR
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Objective Response Rate | By Investigator (n= 87) | 43.7 Percentage of participants |
| Trastuzumab + 2nd Line Chemotherapy | Objective Response Rate | By computer (n=87) | 43.7 Percentage of participants |
Secondary
Overall Survival
Overall Survival is defined as the time (number of days) between enrollment and the date of death due to any cause. Overall survival was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Time frame: Up to 5 years
Population: The Full-Analysis-Set included all participants who were enrolled and had at least one valid primary efficacy variable on active treatment. Only those participants with data available were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab + 2nd Line Chemotherapy | Overall Survival | 717 Days |