HER2 Positive Breast Cancer, Metastatic Breast Cancer, Locally Advanced Breast Cancer
Conditions
Brief summary
This is a Phase IV, single-arm, multicenter, open-label clinical trial designed to assess the safety of trastuzumab emtansine in Indian patients with HER2-positive unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (mBC) who have received prior treatment with trastuzumab and a taxane.
Interventions
DRUGTrastuzumab emtansine
3.6 mg/kg intravenously (IV) over 30-90 minutes on day 1 of 21 day cycle, repeated every 3 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Prospectively confirmed HER2-positive (i.e., IHC 3+ or IHC 2+ and gene amplified by fluorescence in situ hybridization \[FISH\] positive) as assessed on primary tumor and/or metastatic site * Documented progression of unresectable, locally advanced, or mBC, determined by the investigator * Left ventricular ejection fraction (LVEF) \>/= 50% by echocardiogram (ECHO) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * A negative serum Beta-Human Chorionic Gonadotropin (Beta-HCG) test for women of childbearing potential (premenopausal or not meeting the definition of postmenopausal i.e. \>/= 12 months of amenorrhea), and women who have not undergone surgical sterilization (i.e., absence of ovaries and/or uterus) * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate non-hormonal methods of contraception, including at least one method with a failure rate of \<1% per year, during the treatment period and for at least 7 months after the last dose of study drug * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm. With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \<1% per year during the treatment period and for at least 7 months plus 90 days (a spermatogenesis cycle) after the last dose of study drug. Men must refrain from donating sperm during this same period. With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 7 months after the last dose of study drug.
Exclusion criteria
* Prior treatment with trastuzumab emtansine * Prior treatment with lapatinib or lapatinib with capecitabine or non-comparable biologic or biosimilar of trastuzumab * Peripheral neuropathy of Grade \>/= 3 per the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE \[version 4.03\]) * History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, synchronous or previously diagnosed HER2-positive breast cancer, or cancers with a similar curative outcome as those mentioned above * History of receiving any anti-cancer drug/biologic or investigational treatment within 21 days prior to enrollment except hormone therapy, which can be given up to 7 days prior to enrollment; recovery of treatment-related toxicity consistent with other eligibility criteria * History of exposure to cumulative doses of anthracyclines, as defined in the protocol * History of radiation therapy within 14 days of enrollment * Brain metastases that are untreated, symptomatic, or require therapy to control symptoms, as well as a history of radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 2 months (60 days) before enrollment * CNS only disease * History of a decrease in LVEF to \< 40% or symptomatic congestive heart failure (CHF) with previous trastuzumab treatment * History of symptomatic chronic heart failure (New York Heart Association \[NYHA\] Classes II-IV) or serious cardiac arrhythmia requiring treatment * History of myocardial infarction or unstable angina within 6 months of enrollment * Current dyspnea at rest due to complications of advanced malignancy or requirement for continuous oxygen therapy * Current severe, uncontrolled systemic disease * Pregnancy or lactation * Concurrent, serious, uncontrolled infections or current known infection with human immunodeficiency virus (HIV) or active hepatitis B and/or hepatitis C. For patients who are known carriers of hepatitis B virus (HBV), active hepatitis B infection must be ruled out, based on negative serologic testing and/or determination of HBV DNA viral load per local guidelines * Presence of conditions that could affect gastrointestinal absorption: malabsorption syndrome, resection of the small bowel or stomach, and ulcerative colitis * History of intolerance (such as Grade 3-4 infusion reaction) or known hypersensitivity to trastuzumab or murine proteins or any component of the product * Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severity of Adverse Events | From cycle 1 up to approximately 3 years | Adverse events (AEs) grading was completed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. |
| Percentage of Participants With Adverse Events | From cycle 1 up to approximately 3 years | An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study were also considered as adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Non-Serious Adverse Events of Special Interest | From cycle 1 up to approximately 3 years | Non-serious AEs of special interest included cases of severe drug-induced liver injury and suspected transmission of an infectious agent by the study drug. |
| Laboratory Results Abnormalities | From cycle 1 up to approximately 3 years | — |
| Percentage of Participants With Adverse Events Leading to Discontinuation of Study Medication | From cycle 1 up to approximately 3 years | — |
| Percentage of Participants With Adverse Events Leading to Modification of Study Medication | From cycle 1 up to approximately 3 years | — |
| Percentage of Participants With Adverse Events Leading to Interruption of Study Medication | From cycle 1 up to approximately 3 years | — |
| Exposure to Study Drug | From cycle 1 up to approximately 3 years | Exposure to study drug was the amount of study drug received over time (weeks). |
| Percentage of Participants With Serious Adverse Events (SAEs) | From cycle 1 up to approximately 3 years | SAEs were defined as any AE that fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/ birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here. |
| Percentage of Participants With Congestive Heart Failure | From cycle 1 up to approximately 3 years | — |
| Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | From baseline to every three cycles of treatment up to Cycle 39 Day 1, and at the 2-days post-treatment, safety follow-up visits 1 and 3 | — |
| Overall Response Rate (ORR) | From cycle 1 up to approximately 3 years | ORR was based on the best (confirmed) overall response (BOR). ORR was defined as the number (%) of participants with confirmed complete response (CR) or partial response (PR) where the confirmation was performed no less than 4 weeks after the criteria for response were first met. |
| Progression-Free Survival (PFS) | From cycle 1 up to approximately 3 years | PFS was defined as the time from the date of enrollment until the date of first documented progression of disease or the date of death (by any cause in the absence of progression) whichever occurred first. |
| Overall Survival (OS) | From cycle 1 up to approximately 3 years | Overall survival was defined as the time from the date of enrollment until the date of death due to any cause. Participants not known to have died at the time of final analysis were censored based on the last recorded date on which the subject was known to be alive. |
| Percentage of Participants With Drug-Induced Liver Injury Meeting Hy's Law Criteria | From cycle 1 up to approximately 3 years | Hy's law criteria for potential drug-induced liver injury included elevated aminotransferase enzymes (ALT/AST) with concurrent elevated serum total bilirubin, gross jaundice, clinical disability and the need for hospital care. |
| Severity of SAEs as Per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 | From cycle 1 up to approximately 3 years | Severity refered to the intensity of an AE (e.g., rated as mild, moderate, or severe, or according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria. |
Countries
India
Participant flow
Recruitment details
The study was conducted at 13 centres across India.
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab Emtansine 3.6 mg/kg of trastuzumab emtansine was administered to participants intravenously (IV) over 30-90 minutes on day 1 of 21 day cycle and was repeated every 3 weeks. | 70 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 4 |
| Overall Study | Disease Progression | 28 |
| Overall Study | Lost to Follow-up | 7 |
| Overall Study | Withdrawal of Consent | 16 |
Baseline characteristics
| Characteristic | Trastuzumab Emtansine |
|---|---|
| Age, Continuous | 50 Years STANDARD_DEVIATION 11.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 70 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 70 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 12 / 70 |
| other Total, other adverse events | 51 / 70 |
| serious Total, serious adverse events | 28 / 70 |
Outcome results
Primary
Percentage of Participants With Adverse Events
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study were also considered as adverse events.
Time frame: From cycle 1 up to approximately 3 years
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Emtansine | Percentage of Participants With Adverse Events | 90.0 Percentage of Participants |
Primary
Severity of Adverse Events
Adverse events (AEs) grading was completed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.
Time frame: From cycle 1 up to approximately 3 years
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Trastuzumab Emtansine | Severity of Adverse Events | Grade 1 | 53 Participants |
| Trastuzumab Emtansine | Severity of Adverse Events | Grade 2 | 40 Participants |
| Trastuzumab Emtansine | Severity of Adverse Events | Grade 3 | 18 Participants |
| Trastuzumab Emtansine | Severity of Adverse Events | Grade 4 | 2 Participants |
| Trastuzumab Emtansine | Severity of Adverse Events | Grade 5 | 12 Participants |
Secondary
Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram
Time frame: From baseline to every three cycles of treatment up to Cycle 39 Day 1, and at the 2-days post-treatment, safety follow-up visits 1 and 3
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Baseline | 59.49 Percentage of LVEF | Standard Deviation 3.33 |
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Cycle 03 Day 1 | 0.08 Percentage of LVEF | Standard Deviation 3.26 |
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Cycle 06 Day 1 | 0.20 Percentage of LVEF | Standard Deviation 4.5 |
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Cycle 09 Day 1 | 0.23 Percentage of LVEF | Standard Deviation 3.76 |
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Cycle 12 Day 1 | 0.06 Percentage of LVEF | Standard Deviation 4.24 |
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Cycle 15 Day 1 | 0.38 Percentage of LVEF | Standard Deviation 4.4 |
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Cycle 18 Day 1 | 0.15 Percentage of LVEF | Standard Deviation 5.98 |
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Cycle 21 Day 1 | 2.50 Percentage of LVEF | Standard Deviation 3.78 |
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Cycle 24 Day 1 | 0.23 Percentage of LVEF | Standard Deviation 2.89 |
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Cycle 27 Day 1 | -0.60 Percentage of LVEF | Standard Deviation 3.86 |
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Cycle 30 Day 1 | -0.17 Percentage of LVEF | Standard Deviation 1.33 |
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Cycle 33 Day 1 | -1.20 Percentage of LVEF | Standard Deviation 2.39 |
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Cycle 36 Day 1 | 0 Percentage of LVEF | — |
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Cycle 39 Day 1 | 0 Percentage of LVEF | — |
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Safety Follow-Up 1 | 1.28 Percentage of LVEF | Standard Deviation 3.8 |
| Trastuzumab Emtansine | Change in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram | Safety Follow-Up 3 | 1.38 Percentage of LVEF | Standard Deviation 4 |
Secondary
Exposure to Study Drug
Exposure to study drug was the amount of study drug received over time (weeks).
Time frame: From cycle 1 up to approximately 3 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trastuzumab Emtansine | Exposure to Study Drug | 39.60 Weeks | Standard Deviation 32 |
Secondary
Laboratory Results Abnormalities
Time frame: From cycle 1 up to approximately 3 years
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Basophils - High | 1 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Basophils/Leukocytes - Low | 13 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Basophils/Leukocytes - High | 6 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Monocytes - High | 2 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Hematocrit - Low | 57 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Hematocrit - High | 1 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Lymphocytes/Leukocytes - Low | 38 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Lymphocytes/Leukocytes - High | 19 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Monocytes/Leukocytes - Low | 8 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Monocytes/Leukocytes - High | 21 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Neutrophils/Leukocytes - Low | 14 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Neutrophils/Leukocytes - High | 13 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Other Cells - High | 3 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Other Cells/Leukocytes - High | 6 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Erythrocytes - Low | 41 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Erythrocytes - High | 15 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Eosinophils/Leukocytes - Low | 33 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Eosinophils/Leukocytes - High | 13 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Bilirubin - Low | 5 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Bilirubin - High | 22 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Bicarbonate - Low | 4 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Bicarbonate - High | 11 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Direct Bilirubin - High | 27 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Blood Urea Nitrogen - Low | 21 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Blood Urea Nitrogen - High | 10 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Chloride - Low | 20 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Chloride - High | 30 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Lactate Dehydrogenase - Low | 8 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Lactate Dehydrogenase - High | 52 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Protein - Low | 10 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Protein - High | 30 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Urea - Low | 21 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Urea - High | 10 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Partial Thromboplastin Time - Low | 22 Number of Participants |
| Trastuzumab Emtansine | Laboratory Results Abnormalities | Partial Thromboplastin Time - High | 37 Number of Participants |
Secondary
Overall Response Rate (ORR)
ORR was based on the best (confirmed) overall response (BOR). ORR was defined as the number (%) of participants with confirmed complete response (CR) or partial response (PR) where the confirmation was performed no less than 4 weeks after the criteria for response were first met.
Time frame: From cycle 1 up to approximately 3 years
Population: ITT population included all participants enrolled in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trastuzumab Emtansine | Overall Response Rate (ORR) | 16 Participants |
Secondary
Overall Survival (OS)
Overall survival was defined as the time from the date of enrollment until the date of death due to any cause. Participants not known to have died at the time of final analysis were censored based on the last recorded date on which the subject was known to be alive.
Time frame: From cycle 1 up to approximately 3 years
Population: ITT population included all participants enrolled in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Emtansine | Overall Survival (OS) | NA Months |
Secondary
Percentage of Participants With Adverse Events Leading to Discontinuation of Study Medication
Time frame: From cycle 1 up to approximately 3 years
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Emtansine | Percentage of Participants With Adverse Events Leading to Discontinuation of Study Medication | 8.6 Percentage of Participants |
Secondary
Percentage of Participants With Adverse Events Leading to Interruption of Study Medication
Time frame: From cycle 1 up to approximately 3 years
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Emtansine | Percentage of Participants With Adverse Events Leading to Interruption of Study Medication | 15.7 Percentage of Participants |
Secondary
Percentage of Participants With Adverse Events Leading to Modification of Study Medication
Time frame: From cycle 1 up to approximately 3 years
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Trastuzumab Emtansine | Percentage of Participants With Adverse Events Leading to Modification of Study Medication | Dose Reduced | 1 Participants |
| Trastuzumab Emtansine | Percentage of Participants With Adverse Events Leading to Modification of Study Medication | Drug Interrupted | 11 Participants |
Secondary
Percentage of Participants With Congestive Heart Failure
Time frame: From cycle 1 up to approximately 3 years
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Emtansine | Percentage of Participants With Congestive Heart Failure | 0 Percetnage of Participants |
Secondary
Percentage of Participants With Drug-Induced Liver Injury Meeting Hy's Law Criteria
Hy's law criteria for potential drug-induced liver injury included elevated aminotransferase enzymes (ALT/AST) with concurrent elevated serum total bilirubin, gross jaundice, clinical disability and the need for hospital care.
Time frame: From cycle 1 up to approximately 3 years
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Emtansine | Percentage of Participants With Drug-Induced Liver Injury Meeting Hy's Law Criteria | 0 Percentage of Participants |
Secondary
Percentage of Participants With Non-Serious Adverse Events of Special Interest
Non-serious AEs of special interest included cases of severe drug-induced liver injury and suspected transmission of an infectious agent by the study drug.
Time frame: From cycle 1 up to approximately 3 years
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Emtansine | Percentage of Participants With Non-Serious Adverse Events of Special Interest | 2.9 Percentage of Participants |
Secondary
Percentage of Participants With Serious Adverse Events (SAEs)
SAEs were defined as any AE that fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/ birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.
Time frame: From cycle 1 up to approximately 3 years
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Emtansine | Percentage of Participants With Serious Adverse Events (SAEs) | 40 Percentage of Participants |
Secondary
Progression-Free Survival (PFS)
PFS was defined as the time from the date of enrollment until the date of first documented progression of disease or the date of death (by any cause in the absence of progression) whichever occurred first.
Time frame: From cycle 1 up to approximately 3 years
Population: ITT population included all participants enrolled in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Emtansine | Progression-Free Survival (PFS) | 14.0 Months |
Secondary
Severity of SAEs as Per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03
Severity refered to the intensity of an AE (e.g., rated as mild, moderate, or severe, or according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria.
Time frame: From cycle 1 up to approximately 3 years
Population: Safety Population included all enrolled participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Trastuzumab Emtansine | Severity of SAEs as Per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 | Grade 1 | 1 Participants |
| Trastuzumab Emtansine | Severity of SAEs as Per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 | Grade 2 | 13 Participants |
| Trastuzumab Emtansine | Severity of SAEs as Per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 | Grade 3 | 10 Participants |
| Trastuzumab Emtansine | Severity of SAEs as Per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 | Grade 4 | 3 Participants |
| Trastuzumab Emtansine | Severity of SAEs as Per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 | Grade 5 | 6 Participants |