Metastatic Breast Cancer
Conditions
Keywords
Metastatic breast cancer, nab paclitaxel, docetaxel,
Brief summary
This was an open-label study conducted comparing the toxicity and antitumor activity of ABI-007 (Abraxane®, nab®-paclitaxel) to docetaxel (Taxotere).
Detailed description
This was an open-label, randomized study to compare the following regimens with respect to toxicity and antitumor activity: * the maximum tolerated dose (MTD) of ABI-007 300 mg/m\^2 every 3 weeks; * ABI-007 100 mg/m\^2 administered weekly for 3 weeks with a 1 week rest; * ABI-007 150 mg/m\^2 administered weekly for 3 weeks with a 1 week rest; * the standard dose and schedule of Taxotere (100 mg/m\^2 every 3 weeks).
Interventions
DRUGABI-007
ABI-007 administered by intravenous infusion over 30 minutes at one of three different dosing levels (100, 150 or 300 mg/m\^2) with a treatment cycle length of either 3 or 4 weeks depending upon treatment arm assignment.
DRUGDocetaxel
Docetaxel dosed q3w at 100 mg/m\^2
Sponsors
Celgene
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
Patients had to meet the following criteria to be eligible for the study: 1. Pathologically confirmed adenocarcinoma of the breast. 2. No prior chemotherapy for metastatic breast cancer. 3. Stage IV disease. 4. Measurable disease (must have been ≥ 2.0 cm, except for pulmonary lesions that were well documented on CT scan that were ≥ 1.0 cm). 5. At least 3 weeks since prior cytotoxic chemotherapy (patients should have recovered from all acute effects of such therapy. 6. At least 4 weeks since radiotherapy, with full recovery. The measurable disease was completely outside the radiation portal or there was radiologic or clinical exam proof of progressive disease within the radiation portal. 7. At least 4 weeks since major surgery, with full recovery. 8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 9. Age ≥18 years. 10. Patient had the following blood counts at Baseline: * Absolute neutrophil count (ANC) ≥1.5\*10\^9 cells/L * Platelets ≥100\*10\^9 cells/L * Hemoglobin (Hgb) ≥9 g/dL. 11. Patient had the following baseline blood chemistry levels: * Aspartate aminotransferase (AST \[SGOT\]), alanine aminotransferase (ALT \[SGPT\])≥2.5x upper limit of normal (ULN) range * Total bilirubin normal * Alkaline phosphatase ≥2.5x ULN (unless bone metastasis is present in the absence of liver metastasis) * Creatinine ≥1.5 mg/dL. 12. Peripheral neuropathy Grade 0 or 1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). 13. If female of childbearing potential, pregnancy test was negative (within 72 hours of the first dose of study drug). 14. If fertile, the patient agreed to use an effective method to avoid pregnancy for the duration of the study. 15. Informed consent had been obtained.
Exclusion criteria
Patients who met any of the following criteria were excluded from the study: 1. Prior neo-adjuvant or adjuvant chemotherapy was allowed. No prior chemotherapy for metastatic disease was allowed. If a taxane was part of the adjuvant regimen, at least one year should have transpired since completion of taxane regimen. 2. Cumulative life-time dose of doxorubicin \>360 mg/m\^2. Doxorubicin was allowed as prior neo-adjuvant or adjuvant therapy but not for metastatic disease. 3. Concurrent immunotherapy or hormonal therapy for breast cancer. 4. Parenchymal brain metastases, unless documented to be clinically and radiographically stable for at least 6 months after treatment. 5. Serious intercurrent medical or psychiatric illness, including serious active infection. 6. History of class II-IV congestive heart failure. 7. History of other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer. 8. Patients who had received an investigational drug within the previous 3 weeks. 9. Patient was enrolled in a different clinical study in which investigational procedures were performed or investigational therapies were administered. Also, a patient was not permitted enroll in such clinical trials while participating in this study. 10. Pregnant or nursing women 11. Patients with prior hypersensitivity to either Taxol or Taxotere.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator | Day 1 up to 95 weeks | Percentage of participants who achieve an objective confirmed complete or partial overall response based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. A complete response (CR) is the disappearance of all known disease and no new sites or disease related symptoms. A partial response (PR) is \>= 30% decrease in the sum of the longest diameters of target lesion. PR was also recorded when all measurable disease has completely disappeared, but a non-measurable component (ie, ascites) is still present but not progressing. Overall response (ORR) = CR+PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimate for Overall Survival (OS) | Day 1 to 221 weeks | Participant survival was defined as the date of randomization to the date of death. Participants that were alive at the time of analysis were censored at the last known time that the participant was alive. The final analysis of mature overall survival was conducted after 2 years of follow-up (data cutoff date 31 Jan 2010). |
| Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response | Day 1 up to 95 weeks | Known as the disease control rate, this outcome measures the percentage of participants with stable disease for 16 weeks or more, or had a confirmed complete or partial response (see outcome #1 for confirmed response definitions). Assessments made by independent radiology and by investigators are reported separately |
| Kaplan-Meier Estimates for Progression-free Survival (PFS) | Day 1 up to 95 weeks | PFS was defined as the time from the date of randomization to the start of disease progression (PD) or patient death (any cause), whichever occurred first. Patients without disease progression were censored at the last time the patient was known to be progression-free. Patients who initiated new anticancer therapy prior to documented progression or death were censored at the start of new therapy. Disease progression was assessed separately by investigators and by an independent radiologist. Both assessments are offered. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000). PD for target lesions is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion. |
| Kaplan-Meier Estimates for Duration of Response Based on Investigator Assessment of Response and Progression | Day 1 - 95 weeks | Duration of response was measured as the progression-free survival on patients with confirmed response. The investigator assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3. |
| Participants With Treatment-Emergent, Treatment-Related Adverse Events | Day 1 up to 125 weeks | Summary of participants who had treatment-emergent that were treatment-related in the opinion of the investigator, and summarized in a variety of categories. The National Cancer Institute (NCI)'s Common Terminology Criteria for AEs (CTCAE) was used to grade AE severity: severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE. Severity grade 5 = death. |
| Kaplan-Meier Estimates for Duration of Response Based on Independent Radiology Assessment of Response and Progression | Day 1 - 95 weeks | Duration of response was measured as the progression-free survival on patients with confirmed response. The independent radiology assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts | Day 1 up to 125 weeks | Maximal degree of myelosuppression is represented by the nadir in absolute neutrophil (ANC), white blood cell (WBC), and platelet measurements over all treatment cycles. |
| Nadir of Myelosuppression (Over All Cycles) as Measured by Hemoglobin (Hb) Counts | Day 1 up to 125 weeks | Maximal degree of myelosuppression is represented by the nadir in hemoglobin (Hb) measurements over all treatment cycles. |
Countries
Ukraine
Participant flow
Pre-assignment details
Three hundred and two patients were enrolled and randomized between November 2005 and June 2006, of which 300 received study drug and were evaluated for response and safety. Data below represents data cut-off 31 March 2008.
Participants by arm
| Arm | Count |
|---|---|
| ABI-007 300 mg/m^2 q3w ABI-007 300 mg/m\^2 administered once every third week (q3w). | 76 |
| ABI-007 100 mg/m^2 Weekly ABI-007 100 mg/m\^2 once weekly for 3 weeks followed by 1 week of rest | 76 |
| ABI-007 150 mg/m^2 ABI-007 150 mg/m\^2 once weekly for 3 weeks followed by 1 week of rest. | 74 |
| Docetaxel 100 mg/m^2 q3w Docetaxel (Taxotere) 100 mg/m\^2 administered once every third week (q3w). | 74 |
| Total | 300 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 2 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 7 | 5 | 6 | 13 |
| Overall Study | Still on treatment | 2 | 3 | 5 | 1 |
| Overall Study | Unacceptable toxicity | 10 | 5 | 12 | 16 |
| Overall Study | Withdrawal by Subject | 18 | 13 | 9 | 13 |
Baseline characteristics
| Characteristic | Total | Docetaxel 100 mg/m^2 q3w | ABI-007 300 mg/m^2 q3w | ABI-007 150 mg/m^2 | ABI-007 100 mg/m^2 Weekly |
|---|---|---|---|---|---|
| Age, Continuous | 53.9 years STANDARD_DEVIATION 10.05 | 55.4 years STANDARD_DEVIATION 11.57 | 51.7 years STANDARD_DEVIATION 9.47 | 53.3 years STANDARD_DEVIATION 9.14 | 55.4 years STANDARD_DEVIATION 9.59 |
| Age, Customized <65 years | 248 Participants | 55 Participants | 67 Participants | 64 Participants | 62 Participants |
| Age, Customized >=65 years | 52 Participants | 19 Participants | 9 Participants | 10 Participants | 14 Participants |
| Current Site of Metastasis/Relapse Abdomen/Peritoneal | 34 Participants | 7 Participants | 12 Participants | 4 Participants | 11 Participants |
| Current Site of Metastasis/Relapse Axilla | 182 Participants | 44 Participants | 43 Participants | 47 Participants | 48 Participants |
| Current Site of Metastasis/Relapse Bone | 105 Participants | 25 Participants | 22 Participants | 33 Participants | 25 Participants |
| Current Site of Metastasis/Relapse Breast | 42 Participants | 11 Participants | 10 Participants | 11 Participants | 10 Participants |
| Current Site of Metastasis/Relapse Hepatic/Liver | 97 Participants | 25 Participants | 21 Participants | 23 Participants | 28 Participants |
| Current Site of Metastasis/Relapse Lung/Thoracic | 211 Participants | 58 Participants | 53 Participants | 51 Participants | 49 Participants |
| Current Site of Metastasis/Relapse Other | 7 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Current Site of Metastasis/Relapse Pelvis | 4 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants |
| Current Site of Metastasis/Relapse Skin/Soft Tissue | 68 Participants | 19 Participants | 16 Participants | 15 Participants | 18 Participants |
| Current Site of Metastasis/Relapse Supraclavicular | 93 Participants | 25 Participants | 23 Participants | 20 Participants | 25 Participants |
| Dominant Current Site of Metastasis/Relapse Non-visceral | 49 Participants | 7 Participants | 12 Participants | 15 Participants | 15 Participants |
| Dominant Current Site of Metastasis/Relapse Visceral | 251 Participants | 67 Participants | 64 Participants | 59 Participants | 61 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (fully active) | 119 participants | 28 participants | 34 participants | 24 participants | 33 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (restrictive but ambulatory) | 163 participants | 44 participants | 35 participants | 45 participants | 39 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 (ambulatory but unable to work) | 18 participants | 2 participants | 7 participants | 5 participants | 4 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 3 (limited self-care) + 4 (completely disabled) | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Menopausal Status Post-menopausal | 224 Participants | 60 Participants | 49 Participants | 53 Participants | 62 Participants |
| Menopausal Status Pre-menopausal | 73 Participants | 12 Participants | 26 Participants | 21 Participants | 14 Participants |
| Menopausal Status Unknown | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| Number of Lesions (Target + Non-Target) 0 lesions | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Number of Lesions (Target + Non-Target) 1 lesion | 8 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants |
| Number of Lesions (Target + Non-Target) 2-3 lesions | 40 Participants | 10 Participants | 11 Participants | 6 Participants | 13 Participants |
| Number of Lesions (Target + Non-Target) >3 lesions | 252 Participants | 60 Participants | 63 Participants | 67 Participants | 62 Participants |
| Physician Assessment of Sensory Neuropathy Grade 0 | 269 Participants | 67 Participants | 67 Participants | 65 Participants | 70 Participants |
| Physician Assessment of Sensory Neuropathy Grade 1 | 31 Participants | 7 Participants | 9 Participants | 9 Participants | 6 Participants |
| Race/Ethnicity, Customized White, Hispanic or Latino | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White, Non-Hispanic, Non-Latino | 297 Participants | 74 Participants | 74 Participants | 74 Participants | 75 Participants |
| Sex: Female, Male Female | 300 Participants | 74 Participants | 76 Participants | 74 Participants | 76 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Stage at Primary Diagnosis Stage I | 11 participants | 2 participants | 2 participants | 3 participants | 4 participants |
| Stage at Primary Diagnosis Stage IIa | 48 participants | 13 participants | 11 participants | 11 participants | 13 participants |
| Stage at Primary Diagnosis Stage IIb | 47 participants | 15 participants | 12 participants | 13 participants | 7 participants |
| Stage at Primary Diagnosis Stage IIIa | 34 participants | 6 participants | 11 participants | 7 participants | 10 participants |
| Stage at Primary Diagnosis Stage IIIb | 50 participants | 13 participants | 14 participants | 9 participants | 14 participants |
| Stage at Primary Diagnosis Stage IIIc | 3 participants | 1 participants | 0 participants | 0 participants | 2 participants |
| Stage at Primary Diagnosis Stage IV | 97 participants | 21 participants | 23 participants | 28 participants | 25 participants |
| Stage at Primary Diagnosis Unknown | 10 participants | 3 participants | 3 participants | 3 participants | 1 participants |
| Time from Primary Diagnosis and from First Metastasis/Relapse to Study Entry Time from First Metastasis/Relapse to Study Entry | 0.04 Years | 0.04 Years | 0.02 Years | 0.05 Years | 0.04 Years |
| Time from Primary Diagnosis and from First Metastasis/Relapse to Study Entry Time from Primary Diagnosis to Study Entry | 1.23 Years | 1.27 Years | 1.24 Years | 0.97 Years | 1.17 Years |
| Weight | 74.59 Kg STANDARD_DEVIATION 13.742 | 75.99 Kg STANDARD_DEVIATION 14.034 | 72.56 Kg STANDARD_DEVIATION 12.668 | 76.24 Kg STANDARD_DEVIATION 13.437 | 73.64 Kg STANDARD_DEVIATION 14.67 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 75 / 76 | 75 / 76 | 73 / 74 | 73 / 74 |
| serious Total, serious adverse events | 14 / 76 | 12 / 76 | 11 / 74 | 56 / 74 |
Outcome results
Primary
Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator
Percentage of participants who achieve an objective confirmed complete or partial overall response based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. A complete response (CR) is the disappearance of all known disease and no new sites or disease related symptoms. A partial response (PR) is \>= 30% decrease in the sum of the longest diameters of target lesion. PR was also recorded when all measurable disease has completely disappeared, but a non-measurable component (ie, ascites) is still present but not progressing. Overall response (ORR) = CR+PR.
Time frame: Day 1 up to 95 weeks
Population: The treated population consisted of all randomized participants who received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABI-007 300 mg/m^2 q3w | Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator | Independent reader assessed ORR | 37 percentage of participants |
| ABI-007 300 mg/m^2 q3w | Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator | Investigator assessed ORR | 46 percentage of participants |
| ABI-007 100 mg/m^2 Weekly | Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator | Investigator assessed ORR | 63 percentage of participants |
| ABI-007 100 mg/m^2 Weekly | Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator | Independent reader assessed ORR | 45 percentage of participants |
| ABI-007 150 mg/m^2 Weekly | Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator | Independent reader assessed ORR | 49 percentage of participants |
| ABI-007 150 mg/m^2 Weekly | Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator | Investigator assessed ORR | 74 percentage of participants |
| Docetaxel 100 mg/m^2 q3w | Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator | Independent reader assessed ORR | 35 percentage of participants |
| Docetaxel 100 mg/m^2 q3w | Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator | Investigator assessed ORR | 39 percentage of participants |
Comparison: Independent reader assessed ORR. As per the protocol, if the conclusions from the investigator and independent assessments of response rate were the same, the investigator assessment was considered the primary analysis of response rate. If the conclusions were different, the independent radiology reader assessment was considered the primary analysis of response rate. The conclusions were different.p-value: 0.224Cochran-Mantel-Haenszel
Comparison: Investigator assessed ORR. As per the protocol, if the conclusions from the investigator and independent assessments of response rate were the same, the investigator assessment was considered the primary analysis of response rate. If the conclusions were different, the independent radiology reader assessment was considered the primary analysis of response rate. The conclusions were different.p-value: <0.001Cochran-Mantel-Haenszel
Comparison: Investigator assessed ORRp-value: 0.002Cochran-Mantel-Haenszel
Comparison: Investigator assessed ORRp-value: <0.001Cochran-Mantel-Haenszel
Comparison: Investigator assessed ORRp-value: >0.05Cochran-Mantel-Haenszel
Comparison: Investigator assessed ORRp-value: 0.024Cochran-Mantel-Haenszel
Comparison: Investigator assessed ORRp-value: 0.099Cochran-Mantel-Haenszel
Comparison: Investigator assessed ORRp-value: 0.002Cochran-Mantel-Haenszel
Secondary
Kaplan-Meier Estimate for Overall Survival (OS)
Participant survival was defined as the date of randomization to the date of death. Participants that were alive at the time of analysis were censored at the last known time that the participant was alive. The final analysis of mature overall survival was conducted after 2 years of follow-up (data cutoff date 31 Jan 2010).
Time frame: Day 1 to 221 weeks
Population: The treated population consisted of all randomized participants who received at least one dose of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ABI-007 300 mg/m^2 q3w | Kaplan-Meier Estimate for Overall Survival (OS) | 27.7 months |
| ABI-007 100 mg/m^2 Weekly | Kaplan-Meier Estimate for Overall Survival (OS) | 22.2 months |
| ABI-007 150 mg/m^2 Weekly | Kaplan-Meier Estimate for Overall Survival (OS) | 33.8 months |
| Docetaxel 100 mg/m^2 q3w | Kaplan-Meier Estimate for Overall Survival (OS) | 26.6 months |
p-value: 0.047Log Rank
p-value: >0.05Log Rank
p-value: >0.05Log Rank
p-value: >0.05Log Rank
p-value: 0.069Log Rank
p-value: >0.05Log Rank
p-value: 0.008Log Rank
Secondary
Kaplan-Meier Estimates for Duration of Response Based on Independent Radiology Assessment of Response and Progression
Duration of response was measured as the progression-free survival on patients with confirmed response. The independent radiology assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3.
Time frame: Day 1 - 95 weeks
Population: Patients with a confirmed CR or PR were included in this analysis. Patients who did not progress or die were censored at the last known time when patient was progression free. Patients who initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ABI-007 300 mg/m^2 q3w | Kaplan-Meier Estimates for Duration of Response Based on Independent Radiology Assessment of Response and Progression | 13.0 months |
| ABI-007 100 mg/m^2 Weekly | Kaplan-Meier Estimates for Duration of Response Based on Independent Radiology Assessment of Response and Progression | 13.2 months |
| ABI-007 150 mg/m^2 Weekly | Kaplan-Meier Estimates for Duration of Response Based on Independent Radiology Assessment of Response and Progression | 15.1 months |
| Docetaxel 100 mg/m^2 q3w | Kaplan-Meier Estimates for Duration of Response Based on Independent Radiology Assessment of Response and Progression | 9.0 months |
Comparison: Independent assessmentp-value: >0.05Log Rank
Secondary
Kaplan-Meier Estimates for Duration of Response Based on Investigator Assessment of Response and Progression
Duration of response was measured as the progression-free survival on patients with confirmed response. The investigator assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3.
Time frame: Day 1 - 95 weeks
Population: Patients with a confirmed CR or PR were included in this analysis. Patients who did not progress or die were censored at the last known time when patient was progression free. Patients who initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ABI-007 300 mg/m^2 q3w | Kaplan-Meier Estimates for Duration of Response Based on Investigator Assessment of Response and Progression | 12.9 months |
| ABI-007 100 mg/m^2 Weekly | Kaplan-Meier Estimates for Duration of Response Based on Investigator Assessment of Response and Progression | 9.2 months |
| ABI-007 150 mg/m^2 Weekly | Kaplan-Meier Estimates for Duration of Response Based on Investigator Assessment of Response and Progression | 14.8 months |
| Docetaxel 100 mg/m^2 q3w | Kaplan-Meier Estimates for Duration of Response Based on Investigator Assessment of Response and Progression | 15.1 months |
Comparison: Investigator assessmentp-value: 0.013Log Rank
Comparison: Investigator assessmentp-value: 0.022Log Rank
Comparison: Investigator assessmentp-value: >0.05Log Rank
Comparison: Investigator assessmentp-value: >0.05Log Rank
Comparison: Investigator assessmentp-value: 0.005Log Rank
Comparison: Investigator assessmentp-value: >0.05Log Rank
Comparison: Investigator assessmentp-value: >0.05Log Rank
Secondary
Kaplan-Meier Estimates for Progression-free Survival (PFS)
PFS was defined as the time from the date of randomization to the start of disease progression (PD) or patient death (any cause), whichever occurred first. Patients without disease progression were censored at the last time the patient was known to be progression-free. Patients who initiated new anticancer therapy prior to documented progression or death were censored at the start of new therapy. Disease progression was assessed separately by investigators and by an independent radiologist. Both assessments are offered. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000). PD for target lesions is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.
Time frame: Day 1 up to 95 weeks
Population: The treated population consisted of all randomized participants who received at least one dose of study drug
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ABI-007 300 mg/m^2 q3w | Kaplan-Meier Estimates for Progression-free Survival (PFS) | Independent Assessment for PFS | 11.0 months |
| ABI-007 300 mg/m^2 q3w | Kaplan-Meier Estimates for Progression-free Survival (PFS) | Investigator Assessment for PFS | 10.9 months |
| ABI-007 100 mg/m^2 Weekly | Kaplan-Meier Estimates for Progression-free Survival (PFS) | Investigator Assessment for PFS | 7.5 months |
| ABI-007 100 mg/m^2 Weekly | Kaplan-Meier Estimates for Progression-free Survival (PFS) | Independent Assessment for PFS | 12.8 months |
| ABI-007 150 mg/m^2 Weekly | Kaplan-Meier Estimates for Progression-free Survival (PFS) | Independent Assessment for PFS | 12.9 months |
| ABI-007 150 mg/m^2 Weekly | Kaplan-Meier Estimates for Progression-free Survival (PFS) | Investigator Assessment for PFS | 14.6 months |
| Docetaxel 100 mg/m^2 q3w | Kaplan-Meier Estimates for Progression-free Survival (PFS) | Independent Assessment for PFS | 7.5 months |
| Docetaxel 100 mg/m^2 q3w | Kaplan-Meier Estimates for Progression-free Survival (PFS) | Investigator Assessment for PFS | 7.8 months |
Comparison: Independent assessmentp-value: 0.0498Log Rank
Comparison: Independent assessmentp-value: 0.0524Log Rank
Comparison: Independent assessmentp-value: 0.0065Log Rank
Comparison: Independent assessmentp-value: >0.05Log Rank
Comparison: Independent assessmentp-value: >0.05Log Rank
Comparison: Independent assessmentp-value: >0.05Log Rank
Comparison: Independent assessmentp-value: >0.05Log Rank
Comparison: Investigator assessmentp-value: 0.008Log Rank
Comparison: Investigator assessmentp-value: >0.05Log Rank
Comparison: Investigator assessmentp-value: >0.05Log Rank
Comparison: Investigator assessmentp-value: 0.012Log Rank
Comparison: Investigator assessmentp-value: 0.001Log Rank
Comparison: Investigator assessmentp-value: 0.076Log Rank
Comparison: Investigator assessmentp-value: >0.05Log Rank
Secondary
Participants With Treatment-Emergent, Treatment-Related Adverse Events
Summary of participants who had treatment-emergent that were treatment-related in the opinion of the investigator, and summarized in a variety of categories. The National Cancer Institute (NCI)'s Common Terminology Criteria for AEs (CTCAE) was used to grade AE severity: severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE. Severity grade 5 = death.
Time frame: Day 1 up to 125 weeks
Population: The treated population consisted of all randomized participants who received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABI-007 300 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >= 1 adverse event (AE) | 75 participants |
| ABI-007 300 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE | 74 participants |
| ABI-007 300 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 serious AE | 14 participants |
| ABI-007 300 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related serious AE | 13 participants |
| ABI-007 300 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 severe (grade 3-5) treatment-related AE | 47 participants |
| ABI-007 300 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | Grade 3-5 Neutropenia | 33 participants |
| ABI-007 300 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | Grade 3-5 Febrile neutropenia | 1 participants |
| ABI-007 300 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | Grade 3-5 Sensory neuropathy | 16 participants |
| ABI-007 300 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 AE with outcome of death | 0 participants |
| ABI-007 300 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE with outcome of death | 0 participants |
| ABI-007 300 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE drug discontinued | 10 participants |
| ABI-007 300 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE drug dosage reduced | 14 participants |
| ABI-007 300 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE drug interrupted | 1 participants |
| ABI-007 100 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related serious AE | 5 participants |
| ABI-007 100 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE drug interrupted | 1 participants |
| ABI-007 100 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE drug discontinued | 5 participants |
| ABI-007 100 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | Grade 3-5 Sensory neuropathy | 7 participants |
| ABI-007 100 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 serious AE | 12 participants |
| ABI-007 100 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >= 1 adverse event (AE) | 75 participants |
| ABI-007 100 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE with outcome of death | 0 participants |
| ABI-007 100 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 AE with outcome of death | 1 participants |
| ABI-007 100 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | Grade 3-5 Neutropenia | 19 participants |
| ABI-007 100 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 severe (grade 3-5) treatment-related AE | 30 participants |
| ABI-007 100 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE | 72 participants |
| ABI-007 100 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE drug dosage reduced | 13 participants |
| ABI-007 100 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | Grade 3-5 Febrile neutropenia | 1 participants |
| ABI-007 150 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE drug discontinued | 12 participants |
| ABI-007 150 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related serious AE | 8 participants |
| ABI-007 150 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 severe (grade 3-5) treatment-related AE | 49 participants |
| ABI-007 150 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE drug interrupted | 0 participants |
| ABI-007 150 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | Grade 3-5 Neutropenia | 33 participants |
| ABI-007 150 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | Grade 3-5 Febrile neutropenia | 1 participants |
| ABI-007 150 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE drug dosage reduced | 35 participants |
| ABI-007 150 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | Grade 3-5 Sensory neuropathy | 16 participants |
| ABI-007 150 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 AE with outcome of death | 2 participants |
| ABI-007 150 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE with outcome of death | 0 participants |
| ABI-007 150 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >= 1 adverse event (AE) | 73 participants |
| ABI-007 150 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE | 73 participants |
| ABI-007 150 mg/m^2 Weekly | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 serious AE | 11 participants |
| Docetaxel 100 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE with outcome of death | 2 participants |
| Docetaxel 100 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | Grade 3-5 Sensory neuropathy | 9 participants |
| Docetaxel 100 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related serious AE | 55 participants |
| Docetaxel 100 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >= 1 adverse event (AE) | 73 participants |
| Docetaxel 100 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | Grade 3-5 Febrile neutropenia | 8 participants |
| Docetaxel 100 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | Grade 3-5 Neutropenia | 68 participants |
| Docetaxel 100 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 serious AE | 56 participants |
| Docetaxel 100 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE | 72 participants |
| Docetaxel 100 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 severe (grade 3-5) treatment-related AE | 71 participants |
| Docetaxel 100 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 AE with outcome of death | 2 participants |
| Docetaxel 100 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE drug interrupted | 1 participants |
| Docetaxel 100 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE drug dosage reduced | 21 participants |
| Docetaxel 100 mg/m^2 q3w | Participants With Treatment-Emergent, Treatment-Related Adverse Events | >=1 treatment-related AE drug discontinued | 16 participants |
Secondary
Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response
Known as the disease control rate, this outcome measures the percentage of participants with stable disease for 16 weeks or more, or had a confirmed complete or partial response (see outcome #1 for confirmed response definitions). Assessments made by independent radiology and by investigators are reported separately
Time frame: Day 1 up to 95 weeks
Population: The treated population consisted of all randomized participants who received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABI-007 300 mg/m^2 q3w | Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response | Independent Assessed SD Disease Control | 68 percentage of participants |
| ABI-007 300 mg/m^2 q3w | Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response | Investigator Assessed Disease Control | 72 percentage of participants |
| ABI-007 100 mg/m^2 Weekly | Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response | Independent Assessed SD Disease Control | 75 percentage of participants |
| ABI-007 100 mg/m^2 Weekly | Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response | Investigator Assessed Disease Control | 83 percentage of participants |
| ABI-007 150 mg/m^2 Weekly | Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response | Investigator Assessed Disease Control | 91 percentage of participants |
| ABI-007 150 mg/m^2 Weekly | Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response | Independent Assessed SD Disease Control | 80 percentage of participants |
| Docetaxel 100 mg/m^2 q3w | Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response | Investigator Assessed Disease Control | 69 percentage of participants |
| Docetaxel 100 mg/m^2 q3w | Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response | Independent Assessed SD Disease Control | 58 percentage of participants |
Comparison: Independent assessed DCRp-value: 0.027Cochran-Mantel-Haenszel
Comparison: Independent assessed DCRp-value: 0.009Cochran-Mantel-Haenszel
Comparison: Independent assessed DCRp-value: 0.017Cochran-Mantel-Haenszel
Comparison: Independent assessed DCRp-value: >0.05Cochran-Mantel-Haenszel
Comparison: Independent assessed DCRp-value: >0.05Cochran-Mantel-Haenszel
Comparison: Independent assessed DCRp-value: >0.05Cochran-Mantel-Haenszel
Comparison: Independent assessed DCRp-value: 0.085Cochran-Mantel-Haenszel
Comparison: Investigator assessed disease control rate (DCR), ie, SD \>= 16 weeks, or CR or PRp-value: 0.007Cochran-Mantel-Haenszel
Comparison: Investigator assessed DCRp-value: >0.05Cochran-Mantel-Haenszel
Comparison: Investigator assessed DCRp-value: 0.009Cochran-Mantel-Haenszel
Comparison: Investigator assessed DCRp-value: 0.005Cochran-Mantel-Haenszel
Comparison: Investigator assessed DCRp-value: >0.05Cochran-Mantel-Haenszel
Comparison: Investigator assessed DCRp-value: 0.098Cochran-Mantel-Haenszel
Comparison: Investigator assessed DCRp-value: 0.014Cochran-Mantel-Haenszel
Other Pre-specified
Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts
Maximal degree of myelosuppression is represented by the nadir in absolute neutrophil (ANC), white blood cell (WBC), and platelet measurements over all treatment cycles.
Time frame: Day 1 up to 125 weeks
Population: The treated population consisted of all randomized participants who received at least one dose of study drug, and had blood tests performed following treatment. Three participants dropped out after a single dose so have no post-treatment lab values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ABI-007 300 mg/m^2 q3w | Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts | Platelet | 182.1 10^9/L | Standard Deviation 59.16 |
| ABI-007 300 mg/m^2 q3w | Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts | ANC | 1.21 10^9/L | Standard Deviation 1.004 |
| ABI-007 300 mg/m^2 q3w | Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts | WBC | 2.88 10^9/L | Standard Deviation 1.187 |
| ABI-007 100 mg/m^2 Weekly | Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts | WBC | 3.15 10^9/L | Standard Deviation 1.228 |
| ABI-007 100 mg/m^2 Weekly | Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts | ANC | 1.51 10^9/L | Standard Deviation 0.96 |
| ABI-007 100 mg/m^2 Weekly | Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts | Platelet | 192.1 10^9/L | Standard Deviation 57.82 |
| ABI-007 150 mg/m^2 Weekly | Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts | Platelet | 172.6 10^9/L | Standard Deviation 46.39 |
| ABI-007 150 mg/m^2 Weekly | Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts | ANC | 1.11 10^9/L | Standard Deviation 0.628 |
| ABI-007 150 mg/m^2 Weekly | Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts | WBC | 2.68 10^9/L | Standard Deviation 0.817 |
| Docetaxel 100 mg/m^2 q3w | Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts | WBC | 1.60 10^9/L | Standard Deviation 0.726 |
| Docetaxel 100 mg/m^2 q3w | Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts | ANC | 0.38 10^9/L | Standard Deviation 0.339 |
| Docetaxel 100 mg/m^2 q3w | Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts | Platelet | 161.8 10^9/L | Standard Deviation 49.06 |
Other Pre-specified
Nadir of Myelosuppression (Over All Cycles) as Measured by Hemoglobin (Hb) Counts
Maximal degree of myelosuppression is represented by the nadir in hemoglobin (Hb) measurements over all treatment cycles.
Time frame: Day 1 up to 125 weeks
Population: The treated population consisted of all randomized participants who received at least one dose of study drug, and had blood tests performed following treatment. Three participants dropped out after a single dose so have no post-treatment lab values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABI-007 300 mg/m^2 q3w | Nadir of Myelosuppression (Over All Cycles) as Measured by Hemoglobin (Hb) Counts | 112.1 g/L | Standard Deviation 10.58 |
| ABI-007 100 mg/m^2 Weekly | Nadir of Myelosuppression (Over All Cycles) as Measured by Hemoglobin (Hb) Counts | 106.7 g/L | Standard Deviation 10.72 |
| ABI-007 150 mg/m^2 Weekly | Nadir of Myelosuppression (Over All Cycles) as Measured by Hemoglobin (Hb) Counts | 105.6 g/L | Standard Deviation 11.31 |
| Docetaxel 100 mg/m^2 q3w | Nadir of Myelosuppression (Over All Cycles) as Measured by Hemoglobin (Hb) Counts | 107.1 g/L | Standard Deviation 13.39 |