Metastatic Breast Cancer
Conditions
Keywords
Trastuzumab emtansine, MBC, Breast cancer, HER2-positive breast cancer, HER2
Brief summary
This was a multi-institutional, open-label, single-arm, Phase II study of trastuzumab emtansine (T-DM1) administered by intravenous (IV) infusion to patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC).
Interventions
Trastuzumab emtansine was provided in either a liquid or a lyophilized formulation.
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Signed informed consent form. * Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC); tissue (slides or blocks) available for HER2 confirmation. * History of progression on HER2-directed therapy for the treatment of HER2-positive breast cancer. * At least 1, and no more than 3, chemotherapy regimens for MBC. * Granulocyte count ≥ 1500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 9 g/dL. * Serum bilirubin ≤ 1.5 mg/dL, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5x the upper limit of normal (ULN). * Serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 60 mL/min. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Exclusion criteria
* Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biological therapy for the treatment of breast cancer within 2 weeks of the first study treatment. * Prior cumulative doxorubicin dose \> 360 mg/m\^2 or the equivalent. * History of significant cardiac disease, unstable angina, congestive heart failure (CHF), myocardial infarction, or ventricular arrythmia requiring medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST) | Randomization until the analysis data cutoff-dates of 31 Jan 2009 (6 months after the last patient was enrolled in the study) and 25 Jun 2009 (approximately 12 months after the last patient was enrolled in the study, up to 23 months) | Objective response was defined as a complete response (CR) or partial response (PR) determined on 2 consecutive occasions ≥ 4 weeks apart, using Response Evaluation Criteria in Solid Tumors (RECIST). CR: The disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions. PR: Disappearance of all target lesions and persistence of ≥ 1 non-target lesions and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing non-target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Objective Response (OR) Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST) | Randomization until the final analysis cut-off date of 25 Jun 2009 (end of the study, approximately 12 months after the last patient was enrolled, up to 23 months) | For patients who achieved an objective response, duration of objective response was defined as the time from the first tumor assessment that supported a patient's objective response to the time of disease progression or death on study (ie, death from any cause within 30 days of the last dose of study drug), whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. For participants who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate the duration of objective response. |
| Progression-free Survival (PFS) Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST) | Randomization until the final analysis cut-off date of 25 Jun 2009 (end of the study, approximately 12 months after the last patient was enrolled, up to 23 months) | Progression-free survival (PFS) was defined as the time from the first day of study treatment to documented disease progression or death on study (ie, death from any cause within 30 days of the last dose of study drug), whichever occurred first. Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. For patients who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate PFS. |
| Objective Response Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) | Randomization until the final analysis cut-off date of 25 Jun 2009 (end of the study, approximately 12 months after the last patient was enrolled, up to 23 months) | Objective response was defined as a complete response (CR) or partial response (PR) determined on 2 consecutive occasions ≥ 4 weeks apart, using Response Evaluation Criteria in Solid Tumors (RECIST). CR: The disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions. PR: Disappearance of all target lesions and persistence of ≥ 1 non-target lesions and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing non-target lesions. |
| Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) | Randomization until the final analysis cut-off date of 25 Jun 2009 (end of the study, approximately 12 months after the last patient was enrolled, up to 23 months) | For patients who achieved an objective response, duration of objective response was defined as the time from the first tumor assessment that supported a patient's objective response to the time of disease progression or death on study (ie, death from any cause within 30 days of the last dose of study drug), whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. For participants who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate the duration of objective response. |
| Progression-free Survival Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) | Randomization until the final analysis cut-off date of 25 Jun 2009 (end of the study, approximately 12 months after the last patient was enrolled, up to 23 months) | Progression-free survival (PFS) was defined as the time from the first day of study treatment to documented disease progression or death on study (ie, death from any cause within 30 days of the last dose of study drug), whichever occurred first. Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. For patients who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate PFS. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab Emtansine 3.6 mg/kg Patients received trastuzumab emtansine 3.6 mg/kg intravenously on Day 1 of each 21 day cycle for a maximum of 1 year. The total dose was dependent on the patient's weight on Day 1 of each cycle. | 112 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Patient's decision | 1 |
| Overall Study | Physician Decision | 8 |
| Overall Study | Progressive disease | 77 |
| Overall Study | Use of prohibited therapies during study | 1 |
Baseline characteristics
| Characteristic | Trastuzumab Emtansine 3.6 mg/kg |
|---|---|
| Age Continuous | 55.0 years STANDARD_DEVIATION 10.3 |
| Sex: Female, Male Female | 111 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 110 / 112 |
| serious Total, serious adverse events | 30 / 112 |
Outcome results
Primary
Objective Response Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST)
Objective response was defined as a complete response (CR) or partial response (PR) determined on 2 consecutive occasions ≥ 4 weeks apart, using Response Evaluation Criteria in Solid Tumors (RECIST). CR: The disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions. PR: Disappearance of all target lesions and persistence of ≥ 1 non-target lesions and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing non-target lesions.
Time frame: Randomization until the analysis data cutoff-dates of 31 Jan 2009 (6 months after the last patient was enrolled in the study) and 25 Jun 2009 (approximately 12 months after the last patient was enrolled in the study, up to 23 months)
Population: Efficacy evaluable population: All patients who received at least 1 dose of study drug and who underwent a baseline and at least 1 post-baseline tumor assessment or died while in the study from any cause within 30 days of the last dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab Emtansine 3.6 mg/kg | Objective Response Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST) | Month 6 (n=109) | 25.7 Percentage of patients |
| Trastuzumab Emtansine 3.6 mg/kg | Objective Response Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST) | Month 12 (n=108) | 26.9 Percentage of patients |
Secondary
Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
For patients who achieved an objective response, duration of objective response was defined as the time from the first tumor assessment that supported a patient's objective response to the time of disease progression or death on study (ie, death from any cause within 30 days of the last dose of study drug), whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. For participants who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate the duration of objective response.
Time frame: Randomization until the final analysis cut-off date of 25 Jun 2009 (end of the study, approximately 12 months after the last patient was enrolled, up to 23 months)
Population: Patients who had an objective response in the efficacy evaluable population: All patients who received at least 1 dose of study drug and who underwent a baseline and at least 1 post-baseline tumor assessment or died while in the study from any cause within 30 days of the last dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Emtansine 3.6 mg/kg | Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) | 9.4 Months |
Secondary
Duration of Objective Response (OR) Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST)
For patients who achieved an objective response, duration of objective response was defined as the time from the first tumor assessment that supported a patient's objective response to the time of disease progression or death on study (ie, death from any cause within 30 days of the last dose of study drug), whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. For participants who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate the duration of objective response.
Time frame: Randomization until the final analysis cut-off date of 25 Jun 2009 (end of the study, approximately 12 months after the last patient was enrolled, up to 23 months)
Population: Patients who had an objective response in the efficacy evaluable population: All patients who received at least 1 dose of study drug and who underwent a baseline and at least 1 post-baseline tumor assessment or died while in the study from any cause within 30 days of the last dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Emtansine 3.6 mg/kg | Duration of Objective Response (OR) Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST) | NA Months |
Secondary
Objective Response Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
Objective response was defined as a complete response (CR) or partial response (PR) determined on 2 consecutive occasions ≥ 4 weeks apart, using Response Evaluation Criteria in Solid Tumors (RECIST). CR: The disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions. PR: Disappearance of all target lesions and persistence of ≥ 1 non-target lesions and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing non-target lesions.
Time frame: Randomization until the final analysis cut-off date of 25 Jun 2009 (end of the study, approximately 12 months after the last patient was enrolled, up to 23 months)
Population: Efficacy evaluable population: All patients who received at least 1 dose of study drug and who underwent a baseline and at least 1 post-baseline tumor assessment or died while in the study from any cause within 30 days of the last dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Emtansine 3.6 mg/kg | Objective Response Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) | 38.9 Percentage of patients |
Secondary
Progression-free Survival Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
Progression-free survival (PFS) was defined as the time from the first day of study treatment to documented disease progression or death on study (ie, death from any cause within 30 days of the last dose of study drug), whichever occurred first. Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. For patients who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate PFS.
Time frame: Randomization until the final analysis cut-off date of 25 Jun 2009 (end of the study, approximately 12 months after the last patient was enrolled, up to 23 months)
Population: Efficacy evaluable population: All patients who received at least 1 dose of study drug and who underwent a baseline and at least 1 post-baseline tumor assessment or died while in the study from any cause within 30 days of the last dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Emtansine 3.6 mg/kg | Progression-free Survival Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) | 4.6 Months |
Secondary
Progression-free Survival (PFS) Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST)
Progression-free survival (PFS) was defined as the time from the first day of study treatment to documented disease progression or death on study (ie, death from any cause within 30 days of the last dose of study drug), whichever occurred first. Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. For patients who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate PFS.
Time frame: Randomization until the final analysis cut-off date of 25 Jun 2009 (end of the study, approximately 12 months after the last patient was enrolled, up to 23 months)
Population: Efficacy evaluable population: All patients who received at least 1 dose of study drug and who underwent a baseline and at least 1 post-baseline tumor assessment or died while in the study from any cause within 30 days of the last dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Emtansine 3.6 mg/kg | Progression-free Survival (PFS) Assessed by the Independent Review Facility Using Response Evaluation Criteria in Solid Tumors (RECIST) | 4.6 Months |