Metastatic Breast Cancer
Conditions
Keywords
Locally advanced and/or metastatic breast cancer
Brief summary
The purpose of this randomized, Phase 2 open-label study was to assess the response rate of participants with Human Epidermal Growth Factor Receptor 2 (Her2+) locally advanced and/or metastatic breast cancer (not previously treated with chemotherapy or trastuzumab) to treatment with ixabepilone plus trastuzumab and/or docetaxel plus trastuzumab.
Interventions
DRUGixabepilone
Ixabepilone 40 mg/m\^2 was administered as a 3-hour I.V. continuous infusion on Day 1 in a 21-day cycle until disease progression or unacceptable toxicity. For the first cycle, ixabepilone was administered the day following the first dose of trastuzumab (in the first cycle trastuzumab was given on Day 0); in all the following cycles, ixabepilone was administered immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.
DRUGdocetaxel
Docetaxel 100 mg/m\^2 was administered as a 1-hour IV continuous infusion on Day 1 in a 21-day cycle until disease progression or unacceptable toxicity. For the first cycle, docetaxel was administered the day following the first dose of trastuzumab (i.e. in the first cycle trastuzumab was given on Day 0); in all following cycles, docetaxel was administered immediately after trastuzumab if the preceding dose of trastuzumab was well tolerated.
DRUGtrastuzumab
Trastuzumab was administered as an IV infusion on Days 1, 8, and 15 of each 21-day cycle at a dose of 2 mg/kg until disease progression or unacceptable toxicity. In cycle 1, a loading dose of 4 mg/kg was administered as a 90-minute IV infusion on a day before initial administration of chemotherapy (i.e. on Day 0). Trastuzumab was given immediately prior to ixabepilone (Arm A) or docetaxel (Arm B) in all subsequent cycles as a 30-minute IV infusion if the initial dose was well tolerated.
Sponsors
R-Pharm
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
* Locally advanced or metastatic HER2+ breast cancer not previously treated with chemotherapy or trastuzumab. * Subjects who had received prior (neo)adjuvant chemotherapy or trastuzumab were eligible except if they relapsed within 12 months after the last dose of a taxane or trastuzumab given as (neo)adjuvant therapy. * Measurable disease * Left Ventricular Ejection Fraction (LVEF) ≥50%
Exclusion criteria
* Prior chemotherapy or trastuzumab for metastatic breast cancer (MBC) * Relapse within 1 year after (neo)adjuvant taxane or trastuzumab * Neuropathy \> Grade 1 * Significant cardiovascular disease * Any brain metastases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (OR; Assessed by Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1) | Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks) | Percentage of participants with best overall response (BOR) of either complete response (CR) or partial response (PR) according to RECIST version 1.1 as determined by the investigator. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. A two-sided confidence interval (CI) was computed using the Clopper-Pearson method. |
| Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks). | BOR was the best response recorded from the start of treatment until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the LD of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. Refer to Outcome Measure 3 for definition of PD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | From the date of first PR or CR assessment to the date of documented progressive disease or death without prior documentation of progression (maximum participant duration of response of 38 months.) | Period measured in months from time that measurement criteria were first met for CR or PR until first date of documented PD or death from any cause without prior documentation of progression. PD=≥20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall. Refer to Outcome Measure 1 for definitions of CR and PR. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by Brookmeyer and Crowley method. |
| Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.) | AE: New untoward medical occurrence or worsening of a preexisting medical condition that does not have causal relationship with this treatment. SAE: Untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency/abuse; life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization/prolongs existing hospitalization. Grade 3=Severe; and Grade 4=Life-threatening or disabling. GR=Grade. |
| Progression Free Survival (PFS) | From randomization until the first date of documented progressive disease (PD) or death from any cause without prior documentation of progression (maximum participant PFS of 39.7 months). | Time in months from randomization until first date of documented progressive disease (PD) or death from any cause without prior documentation of progression. PD=≥20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by the Brookmeyer and Crowley method. |
| Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.) | Grading: NCI CTCAE, Version 3.0. GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST): GR1=\>ULN-2.5\*ULN; GR2=\>2.5-5.0\*ULN; GR3=\>5.0-20.0\*ULN; GR4=\>20.0\*ULN. Total bilirubin: GR1=\>ULN-1.5\*ULN, GR2=\>1.5-3.0\*ULN, GR3=\>3-10\*ULN, GR4=\>10\*ULN. Creatinine: GR1=\>ULN-1.5\*ULN, GR2=\>1.5-3.0\*ULN, GR3=\>3.0-6.0\*ULN, GR4=\>6.0\*ULN. ULN=upper limit of normal. |
| Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.) | Grade (GR)1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. White blood cell (WBC):GR1=\<LLN-3.0\*10\^9/L; GR2=\<3.0-2.0\*10\^9/L; GR3=\<2.0-1.0\*10\^9/L; GR4=\<1.0\*10\^9/L. Absolute Neutrophil Count (ANC):GR1=\<LLN-1.5\*10\^9 /L; GR2=\<1.5-1.0\*10\^9/L; GR3=\<1.0-0.5\*10\^9/L; GR4=\<0.5\*10\^9/L. Platelets:GR1=\<LLN-75.0\*10\^9/L; GR2=\<75.0-50.0\*10\^9/L; GR3=\<50.0-25.0\*10\^9/L, GR4=\<25.0\*10\^9/L. Hemoglobin:GR1=\<LLN-10.0g/dL; GR2=\<10.0-8.0g/dL; GR3=\<8.0-6.5g/dL, GR4=\<6.5g/dL. LLN=lower limit of normal. |
| Time to Response | From randomization every 6 weeks for first 12 months and thereafter every 3 months until CR or PR whichever was recorded first (maximum participant time to response of 18.4 weeks.) | Time to response was defined as the time in weeks from randomization until the measurement criteria are first met for a CR or PR, whichever is recorded first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the LD of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by the Brookmeyer and Crowley method. |
Countries
France, Greece, Italy, Spain, Turkey (Türkiye)
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m\^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity. | 25 |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m\^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity. | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Never Treated (had an adverse event) | 1 | 0 |
| Overall Study | Never Treated (withdrew consent) | 0 | 1 |
| Overall Study | Still on trastuzumab monotherapy | 1 | 1 |
Baseline characteristics
| Characteristic | Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Total |
|---|---|---|---|
| Age, Continuous | 52.0 years | 53.0 years | 52.5 years |
| Age, Customized < 65 years | 19 participants | 21 participants | 40 participants |
| Age, Customized >=65 years | 6 participants | 4 participants | 10 participants |
| Karnofsky Performance Status 100 | 15 participants | 15 participants | 30 participants |
| Karnofsky Performance Status 70 | 1 participants | 0 participants | 1 participants |
| Karnofsky Performance Status 80 | 4 participants | 0 participants | 4 participants |
| Karnofsky Performance Status 90 | 5 participants | 9 participants | 14 participants |
| Karnofsky Performance Status Not Reported | 0 participants | 1 participants | 1 participants |
| Menopausal Status Not Reported | 2 participants | 2 participants | 4 participants |
| Menopausal Status Peri-menopausal | 1 participants | 2 participants | 3 participants |
| Menopausal Status Post-menopausal | 14 participants | 15 participants | 29 participants |
| Menopausal Status Pre-menopausal | 8 participants | 6 participants | 14 participants |
| Number of participants who received prior chemotherapy in neoadjuvant/adjuvant setting | 8 participants | 8 participants | 16 participants |
| Race/Ethnicity, Customized White | 25 participants | 25 participants | 50 participants |
| Sex/Gender, Customized Female | 25 participants | 25 participants | 50 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 24 | 24 / 24 |
| serious Total, serious adverse events | 13 / 24 | 6 / 24 |
Outcome results
Primary
Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
BOR was the best response recorded from the start of treatment until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the LD of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. Refer to Outcome Measure 3 for definition of PD.
Time frame: Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks).
Population: All randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Stable disease | 6 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Unable to determine (UTD; Death due to toxicity) | 1 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Partial response | 12 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | UTD (reason other than toxicity or progression) | 1 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Progressive disease | 1 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Never treated | 1 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Complete response | 3 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Never treated | 1 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Complete response | 2 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Partial response | 11 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Stable disease | 9 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Progressive disease | 1 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Unable to determine (UTD; Death due to toxicity) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | UTD (reason other than toxicity or progression) | 1 participants |
Primary
Percentage of Participants With Objective Response (OR; Assessed by Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1)
Percentage of participants with best overall response (BOR) of either complete response (CR) or partial response (PR) according to RECIST version 1.1 as determined by the investigator. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. A two-sided confidence interval (CI) was computed using the Clopper-Pearson method.
Time frame: Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks)
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Percentage of Participants With Objective Response (OR; Assessed by Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1) | 60.0 percentage of participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Percentage of Participants With Objective Response (OR; Assessed by Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1) | 52.0 percentage of participants |
Secondary
Duration of Response
Period measured in months from time that measurement criteria were first met for CR or PR until first date of documented PD or death from any cause without prior documentation of progression. PD=≥20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall. Refer to Outcome Measure 1 for definitions of CR and PR. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by Brookmeyer and Crowley method.
Time frame: From the date of first PR or CR assessment to the date of documented progressive disease or death without prior documentation of progression (maximum participant duration of response of 38 months.)
Population: All randomized participants with CR or PR. The participants who neither relapsed nor died were censored on the date of their last tumor assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Duration of Response | 11.5 months |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Duration of Response | 16.5 months |
Secondary
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0
AE: New untoward medical occurrence or worsening of a preexisting medical condition that does not have causal relationship with this treatment. SAE: Untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency/abuse; life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization/prolongs existing hospitalization. Grade 3=Severe; and Grade 4=Life-threatening or disabling. GR=Grade.
Time frame: Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Population: Treated participants: Participants who received at least 1 dose of study therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | All deaths | 1 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | Death within 30 days of last dose of study therapy | 1 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | SAEs (Any Grade) | 6 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | SAEs (Grades 3-4) | 4 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | Drug-related SAEs (Any Grade) | 3 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | Drug-related SAEs (Grades 3-4) | 2 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | AEs (Any Grade) | 24 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | AEs (Grades 3-4) | 19 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | Drug-related AEs (Any Grade) | 24 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | Drug-related AEs (Grades 3-4) | 18 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | AEs leading to discontinuation of therapy (Any GR) | 5 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | AEs leading to discontinuation of therapy (GR 3-4) | 2 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | Drug-related peripheral neuropathy (Any Grade) | 16 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | Drug-related peripheral neuropathy (Grades 3-4) | 2 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | AEs leading to discontinuation of therapy (Any GR) | 9 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | All deaths | 1 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | AEs (Grades 3-4) | 23 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | Death within 30 days of last dose of study therapy | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | Drug-related peripheral neuropathy (Any Grade) | 12 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | SAEs (Any Grade) | 13 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | Drug-related AEs (Any Grade) | 24 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | SAEs (Grades 3-4) | 12 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | AEs leading to discontinuation of therapy (GR 3-4) | 4 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | Drug-related SAEs (Any Grade) | 10 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | Drug-related AEs (Grades 3-4) | 22 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | Drug-related SAEs (Grades 3-4) | 8 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | Drug-related peripheral neuropathy (Grades 3-4) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 | AEs (Any Grade) | 24 participants |
Secondary
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0
Grade (GR)1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. White blood cell (WBC):GR1=\<LLN-3.0\*10\^9/L; GR2=\<3.0-2.0\*10\^9/L; GR3=\<2.0-1.0\*10\^9/L; GR4=\<1.0\*10\^9/L. Absolute Neutrophil Count (ANC):GR1=\<LLN-1.5\*10\^9 /L; GR2=\<1.5-1.0\*10\^9/L; GR3=\<1.0-0.5\*10\^9/L; GR4=\<0.5\*10\^9/L. Platelets:GR1=\<LLN-75.0\*10\^9/L; GR2=\<75.0-50.0\*10\^9/L; GR3=\<50.0-25.0\*10\^9/L, GR4=\<25.0\*10\^9/L. Hemoglobin:GR1=\<LLN-10.0g/dL; GR2=\<10.0-8.0g/dL; GR3=\<8.0-6.5g/dL, GR4=\<6.5g/dL. LLN=lower limit of normal.
Time frame: Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.)
Population: Treated participants: Participants who received at least 1 dose of study therapy. n=number of participants with measures available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | WBC Grade 1 (n=24; n=22) | 6 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | WBC Grade 2 (n=24; n=22) | 7 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | WBC Grade 3 (n=24; n=22) | 8 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | WBC Grade 4 (n=24; n=22) | 1 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ANC Grade 1 (n=23; n=23) | 2 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ANC Grade 2 (n=23; n=23) | 4 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ANC Grade 3 (n=23; n=23) | 8 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ANC Grade 4 (n=23; n=23) | 6 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Platelet Count Grade 1 (n=24; n=23) | 9 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Platelet Count Grade 2 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Platelet Count Grade 3 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Platelet Count Grade 4 (n=24; n=23) | 1 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Hemoglobin Grade 1 (n=24; n=23) | 14 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Hemoglobin Grade 2 (n=24; n=23) | 8 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Hemoglobin Grade 3 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Hemoglobin Grade 4 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Hemoglobin Grade 4 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | WBC Grade 1 (n=24; n=22) | 1 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Platelet Count Grade 1 (n=24; n=23) | 3 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | WBC Grade 2 (n=24; n=22) | 1 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Hemoglobin Grade 1 (n=24; n=23) | 12 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | WBC Grade 3 (n=24; n=22) | 15 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Platelet Count Grade 2 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | WBC Grade 4 (n=24; n=22) | 4 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Hemoglobin Grade 3 (n=24; n=23) | 1 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ANC Grade 1 (n=23; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Platelet Count Grade 3 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ANC Grade 2 (n=23; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Hemoglobin Grade 2 (n=24; n=23) | 8 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ANC Grade 3 (n=23; n=23) | 3 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Platelet Count Grade 4 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ANC Grade 4 (n=23; n=23) | 19 participants |
Secondary
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0
Grading: NCI CTCAE, Version 3.0. GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST): GR1=\>ULN-2.5\*ULN; GR2=\>2.5-5.0\*ULN; GR3=\>5.0-20.0\*ULN; GR4=\>20.0\*ULN. Total bilirubin: GR1=\>ULN-1.5\*ULN, GR2=\>1.5-3.0\*ULN, GR3=\>3-10\*ULN, GR4=\>10\*ULN. Creatinine: GR1=\>ULN-1.5\*ULN, GR2=\>1.5-3.0\*ULN, GR3=\>3.0-6.0\*ULN, GR4=\>6.0\*ULN. ULN=upper limit of normal.
Time frame: Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.)
Population: Treated participants: Participants who received at least 1 dose of study therapy. n=number of participants with measures available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALP Grade 1 (n=23; n=23) | 11 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALP Grade 2 (n=23; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALP Grade 3 (n=23; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALP Grade 4 (n=23; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALT Grade 1 (n=24; n=23) | 10 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALT Grade 2 (n=24; n=23) | 3 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALT Grade 3 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALT Grade 4 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | AST Grade 1 (n=24; n=23) | 13 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | AST Grade 2 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | AST Grade 3 (n=24; n=23) | 1 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | AST Grade 4 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Total Bilirubin Grade 1 (n=24; n=23) | 2 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Total Bilirubin Grade 2 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Total Bilirubin Grade 3 (n=24; n=23) | 1 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Total Bilirubin Grade 4 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Creatinine Grade 1 (n=24; n=23) | 2 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Creatinine Grade 2 (n=24; n=23) | 2 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Creatinine Grade 3 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Creatinine Grade 4 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Creatinine Grade 2 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALP Grade 1 (n=23; n=23) | 8 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | AST Grade 3 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALP Grade 2 (n=23; n=23) | 1 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Total Bilirubin Grade 4 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALP Grade 3 (n=23; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | AST Grade 4 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALP Grade 4 (n=23; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Creatinine Grade 4 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALT Grade 1 (n=24; n=23) | 15 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Total Bilirubin Grade 1 (n=24; n=23) | 2 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALT Grade 2 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Creatinine Grade 1 (n=24; n=23) | 1 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALT Grade 3 (n=24; n=23) | 1 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Total Bilirubin Grade 2 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | ALT Grade 4 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Creatinine Grade 3 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | AST Grade 1 (n=24; n=23) | 11 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | Total Bilirubin Grade 3 (n=24; n=23) | 0 participants |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 | AST Grade 2 (n=24; n=23) | 1 participants |
Secondary
Progression Free Survival (PFS)
Time in months from randomization until first date of documented progressive disease (PD) or death from any cause without prior documentation of progression. PD=≥20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by the Brookmeyer and Crowley method.
Time frame: From randomization until the first date of documented progressive disease (PD) or death from any cause without prior documentation of progression (maximum participant PFS of 39.7 months).
Population: All randomized participants. Participants who did not progress or died were censored on the date of their last tumor assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Progression Free Survival (PFS) | 11.3 months |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Progression Free Survival (PFS) | 13.0 months |
Secondary
Time to Response
Time to response was defined as the time in weeks from randomization until the measurement criteria are first met for a CR or PR, whichever is recorded first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the LD of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by the Brookmeyer and Crowley method.
Time frame: From randomization every 6 weeks for first 12 months and thereafter every 3 months until CR or PR whichever was recorded first (maximum participant time to response of 18.4 weeks.)
Population: All randomized participants with CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | Time to Response | 10.1 weeks |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | Time to Response | 7.3 weeks |