Breast Cancer
Conditions
Brief summary
This single arm study will assess the safety and efficacy of a regimen of Avastin plus a taxane, with or without additional chemotherapy, as first-line treatment in patients with locally recurrent or metastatic breast cancer. All patients will receive Avastin (10mg/kg iv every 2 weeks, or 15 mg/kg iv every 3 weeks) plus taxane-based chemotherapy. If taxanes are contraindicated, alternative chemotherapy (other than anthracyclines or pegylated liposomal doxorubicin) may be used. The anticipated time on study treatment is until disease progression, and the target sample size is 500+ individuals.
Interventions
DRUGbevacizumab [Avastin]
10mg/kg iv on day 1 of each 3 week cycle, or 15mg/kg iv on day 1 of each 2 week cycle
As prescribed
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patients, \>=18 years of age; * HER-2 negative adenocarcinoma of the breast, with locally recurrent or metastatic disease; (HER-2 positive patients only if previously treated with Herceptin in the adjuvant setting; * candidates for chemotherapy.
Exclusion criteria
* previous chemotherapy for metastatic or locally recurrent breast cancer; * concomitant hormonal therapy for metastatic or locally recurrent disease; * concomitant Herceptin therapy for treatment of metastatic or locally recurrent HER-2 positive disease; * previous radiotherapy for treatment of metastatic disease; * evidence of CNS metastases.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Related to Bevacizumab, Death, and AEs of Special Interest (AESIs) | Day 1 of Cycles 1, 2, 3, 4, 5, and 6 up to 6 months after the last bevacizumab infusion | Adverse events (including laboratory abnormalities) were assessed by the investigator according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) grading systems. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Disease Progression | Baseline, Day 1 of Cycle 4, final visit and every 3 months during follow-up until disease progression or death up to 45 months | Disease progression was assessed by the investigator per standard clinical practice using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. |
| Time to Progression (TTP) | Baseline, Day 1 of Cycle 4, final visit and every 3 months during follow-up until disease progression or death up to 45 months | TTP was defined as the time period from the start of first-line therapy to investigator-assessed disease progression. Tumor assessments were performed according to standard clinical practice using NCI criteria. Participants who had not progressed at the time of analysis (including those who died before progressive disease \[PD\]) or who were lost to follow-up were censored at the last bevacizumab administration date. Time to disease progression was determined by Kaplan-Meier estimates. |
| Percentage of Participants With Recorded Death | Baseline, Day 1 of Cycle 4, final visit and every 3 months during follow-up until disease progression or death up to 45 months | — |
| Overall Survival | Baseline, Day 1 of Cycle 4, Final Visit and every 3 months during follow-up until death up to 45 months | Overall Survival was defined as the time from start of first-line therapy to death due to any cause. Participants for whom no death was captured in the clinical database were censored at the last date they were known to be alive. Median time to overall survival was calculated by Kaplan Meier estimates. |
| Percentage of Participants by Best Overall Response to Treatment | Baseline, Day 1 of Cycle 4, final visit and every 3 months during follow-up until disease progression or death up to 45 months | Best overall response is defined as the best response shown throughout the study. Tumor assessment was performed by the investigator using standard clinical practice. |
Countries
Argentina, Australia, Austria, Brazil, Bulgaria, Canada, China, Colombia, Czechia, Ecuador, Egypt, Estonia, Finland, France, Germany, Hong Kong, Hungary, Israel, Italy, Latvia, Lebanon, Lithuania, Mexico, Morocco, Netherlands, Poland, Portugal, Russia, Saudi Arabia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab Participants received bevacizumab 15 mg/kg iv on day 1 of each 3 week cycle, or 10 mg/kg iv on day 1 of each 2 week cycle (weekly equivalent dose of 5 mg/kg/week) until disease progression, unacceptable toxicity or withdrawal, along with Taxane-based chemotherapy as prescribed | 2,264 |
| Total | 2,264 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 382 |
| Overall Study | Lost to Follow-up | 19 |
| Overall Study | Other | 154 |
| Overall Study | Progressive Disease | 1,382 |
| Overall Study | Protocol Violation | 41 |
| Overall Study | Termination of Study | 70 |
| Overall Study | Treatment Regimen Completed | 70 |
| Overall Study | Withdrawal by Subject | 178 |
Baseline characteristics
| Characteristic | Bevacizumab |
|---|---|
| Age, Continuous | 53.2 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 2252 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2,095 / 2,264 |
| serious Total, serious adverse events | 672 / 2,264 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Related to Bevacizumab, Death, and AEs of Special Interest (AESIs)
Adverse events (including laboratory abnormalities) were assessed by the investigator according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) grading systems.
Time frame: Day 1 of Cycles 1, 2, 3, 4, 5, and 6 up to 6 months after the last bevacizumab infusion
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab | Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Related to Bevacizumab, Death, and AEs of Special Interest (AESIs) | Any AE | 95.4 percentage of participants |
| Bevacizumab | Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Related to Bevacizumab, Death, and AEs of Special Interest (AESIs) | CTC grade 3, 4 or 5 AE | 57.6 percentage of participants |
| Bevacizumab | Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Related to Bevacizumab, Death, and AEs of Special Interest (AESIs) | Bevacizumab-related AE | 64.2 percentage of participants |
| Bevacizumab | Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Related to Bevacizumab, Death, and AEs of Special Interest (AESIs) | Any Serious AE | 29.7 percentage of participants |
| Bevacizumab | Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Related to Bevacizumab, Death, and AEs of Special Interest (AESIs) | Bevacizumab-related serious SAE | 7.6 percentage of participants |
| Bevacizumab | Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Related to Bevacizumab, Death, and AEs of Special Interest (AESIs) | All deaths | 53.1 percentage of participants |
| Bevacizumab | Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Related to Bevacizumab, Death, and AEs of Special Interest (AESIs) | AESIs | 71.8 percentage of participants |
Secondary
Overall Survival
Overall Survival was defined as the time from start of first-line therapy to death due to any cause. Participants for whom no death was captured in the clinical database were censored at the last date they were known to be alive. Median time to overall survival was calculated by Kaplan Meier estimates.
Time frame: Baseline, Day 1 of Cycle 4, Final Visit and every 3 months during follow-up until death up to 45 months
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab | Overall Survival | 25.2 months |
Secondary
Percentage of Participants by Best Overall Response to Treatment
Best overall response is defined as the best response shown throughout the study. Tumor assessment was performed by the investigator using standard clinical practice.
Time frame: Baseline, Day 1 of Cycle 4, final visit and every 3 months during follow-up until disease progression or death up to 45 months
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab | Percentage of Participants by Best Overall Response to Treatment | Complete response | 9.0 percentage of participants |
| Bevacizumab | Percentage of Participants by Best Overall Response to Treatment | Partial response | 45.1 percentage of participants |
| Bevacizumab | Percentage of Participants by Best Overall Response to Treatment | Stable disease | 32.4 percentage of participants |
| Bevacizumab | Percentage of Participants by Best Overall Response to Treatment | Progressive disease | 9.1 percentage of participants |
| Bevacizumab | Percentage of Participants by Best Overall Response to Treatment | Not evaluable | 0.1 percentage of participants |
| Bevacizumab | Percentage of Participants by Best Overall Response to Treatment | Assessment not done | 4.2 percentage of participants |
Secondary
Percentage of Participants With Disease Progression
Disease progression was assessed by the investigator per standard clinical practice using Response Evaluation Criteria In Solid Tumors (RECIST) criteria.
Time frame: Baseline, Day 1 of Cycle 4, final visit and every 3 months during follow-up until disease progression or death up to 45 months
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab | Percentage of Participants With Disease Progression | 72.44 percentage of participants |
Secondary
Percentage of Participants With Recorded Death
Time frame: Baseline, Day 1 of Cycle 4, final visit and every 3 months during follow-up until disease progression or death up to 45 months
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab | Percentage of Participants With Recorded Death | 53.14 percentage of participants |
Secondary
Time to Progression (TTP)
TTP was defined as the time period from the start of first-line therapy to investigator-assessed disease progression. Tumor assessments were performed according to standard clinical practice using NCI criteria. Participants who had not progressed at the time of analysis (including those who died before progressive disease \[PD\]) or who were lost to follow-up were censored at the last bevacizumab administration date. Time to disease progression was determined by Kaplan-Meier estimates.
Time frame: Baseline, Day 1 of Cycle 4, final visit and every 3 months during follow-up until disease progression or death up to 45 months
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab | Time to Progression (TTP) | 9.7 months |