Breast Neoplasms
Conditions
Keywords
advanced breast cancer, sunitinib, docetaxel, Phase 3
Brief summary
This is a phase 3 randomized trial evaluating the anti-tumor activity and safety of sunitinib combined with docetaxel versus docetaxel, administered as first-line treatment, in patients with unresectable locally recurrent or metastatic breast cancer.
Interventions
DRUGSunitinib malate
Sunitinib 37.5 mg daily by oral capsule in schedule 2/1 with Docetaxel 75 mg/m2 every 3 weeks or 37. 5 mg daily in continuous dosing (in absence of docetaxel)
DRUGTaxotere
Docetaxel 100 mg/m2 every 3 weeks in the comparator arm
Sponsors
Pfizer
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
* Breast cancer with evidence of unresectable locally recurrent, or metastatic disease * Her-2 negative tumors
Exclusion criteria
* Patients for whom docetaxel is contraindicated * Clinical presentation of inflammatory carcinoma with no other measurable disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Baseline up to Month 33 | PFS defined as time from date of randomization to date of the first documentation of objective tumor progression or death due to any cause, whichever occurred first. PFS calculated as (Months) = (first event date minus randomization date plus 1) divided by 30.4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DR) | Baseline up to Month 33 | DR defined as time from first objective documentation of complete or partial response that was subsequently confirmed to first documentation of disease progression or to death due to any cause, whichever occurred first. DR calculated (Months) = (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. |
| Overall Survival (OS) | Baseline to date of death from any cause (up to Month 33) | Time from randomization to date of death due to any cause. OS calculated as (Months) = (death date minus date of first dose of study medication plus 1) divided by 30.4. For participants who were alive, overall survival was censored at last contact. |
| Percentage of Participants With Objective Response | Baseline up to Month 33 | Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as the disappearance of all tumor lesions (target and non-target). PR defined as greater than or equal to 30 percent (≥30%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions with a non-progressive disease status of the non-target lesions. |
| Change From Baseline in EORTC-QLQ Breast Cancer Module (EORTC-QLQ-BR23) Score | Baseline, every 6 weeks up to end of treatment or early termination (up to Month 33) | EORTC-QLQ-BR23 measured multi-item functional scales for body image, sexual functioning, sexual enjoyment, and future perspective and measured single item symptoms scales which assessed systemic therapy side effects, breast symptoms, arm symptoms, and upset by hair loss. For functional scales, scores ranged from 0 to 100 where higher scores represented a better level of functioning. For symptoms scales, scores ranged from 0 to 100 where higher scores represented a greater degree of symptoms. Change from baseline = score for Cycle/Day minus baseline score. |
| Change From Baseline European Quality of Life 5-dimensional Self-Report Questionnaire (EQ-5D) Score | Baseline, every 6 weeks up to end of treatment or early termination (up to Month 33) | EQ-5D: standardized, participant-administered 2 part measure of health outcome. Part 1: descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), used 3 levels (no, some, extreme problems) and a single index value characterized current health status using formula that weighted the dimensions. Part 2: overall rating of participant's current health used Visual Analog Scale with endpoints labeled 'best imaginable health state' and 'worst imaginable health state'. Change from baseline = score for Cycle/Day minus baseline score. |
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionaire-C30 (EORTC- QLQ-C30) Score | Baseline, every 6 weeks up to end of treatment or early termination (up to Month 33) | EORTC QLQ-C30 measured 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnoea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. For functional domains and global health status, scores ranged from 0 to 100 where higher scores represented a better level of functioning. For symptoms scales, scores ranged from 0 to 100 where higher scores represented a greater degree of symptoms. Change from baseline = score for Cycle/Day minus baseline score. |
Countries
Argentina, Australia, Austria, Belgium, Canada, Colombia, Czechia, Finland, France, Germany, Hungary, Ireland, Italy, Netherlands, Panama, Poland, Portugal, Romania, Russia, Slovakia, South Korea, Spain, Sweden, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
594 participants enrolled in study; 1 participant withdrew consent prior to treatment. In accordance with French law, that participant's data was not used in the analyses.
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel + Sunitinib Sunitinib 37.5 milligrams (mg) daily by oral capsule for 2 weeks followed by a 1-week off-treatment period (Schedule 2/1) with docetaxel 75 milligrams per square meter (mg/m\^2) every 3 weeks, or sunitinib 37.5 mg daily in continuous dosing (in absence of docetaxel), or docetaxel 100 mg/m\^2 every 3 weeks (in absence of sunitinib). | 296 |
| Docetaxel Docetaxel 100 mg/m\^2 every 3 weeks | 297 |
| Total | 593 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 10 | 4 |
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | Objective progression or relapse | 239 | 223 |
| Overall Study | Other | 37 | 45 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Sponsor | 5 | 13 |
| Overall Study | Withdrawal by Subject | 2 | 7 |
Baseline characteristics
| Characteristic | Docetaxel + Sunitinib | Docetaxel | Total |
|---|---|---|---|
| Age Continuous | 54.3 Years STANDARD_DEVIATION 9.74 | 55.1 Years STANDARD_DEVIATION 10.36 | 54.7 Years STANDARD_DEVIATION 10.05 |
| Sex: Female, Male Female | 296 Participants | 297 Participants | 593 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 290 / 295 | 291 / 293 |
| serious Total, serious adverse events | 112 / 295 | 79 / 293 |
Outcome results
Primary
Progression-Free Survival (PFS)
PFS defined as time from date of randomization to date of the first documentation of objective tumor progression or death due to any cause, whichever occurred first. PFS calculated as (Months) = (first event date minus randomization date plus 1) divided by 30.4.
Time frame: Baseline up to Month 33
Population: Intent-to-Treat (ITT) Population: all randomized participants
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Docetaxel + Sunitinib | Progression-Free Survival (PFS) | Investigator's assessment | 8.2 months |
| Docetaxel + Sunitinib | Progression-Free Survival (PFS) | Independent radiology assessment | 8.6 months |
| Docetaxel | Progression-Free Survival (PFS) | Independent radiology assessment | 8.3 months |
| Docetaxel | Progression-Free Survival (PFS) | Investigator's assessment | 6.9 months |
Comparison: Independent radiology assessmentp-value: 0.265195% CI: [0.7156, 1.1885]Log Rank
Comparison: Investigator's assessmentp-value: 0.075395% CI: [0.6921, 1.0589]Log Rank
Secondary
Change From Baseline European Quality of Life 5-dimensional Self-Report Questionnaire (EQ-5D) Score
EQ-5D: standardized, participant-administered 2 part measure of health outcome. Part 1: descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), used 3 levels (no, some, extreme problems) and a single index value characterized current health status using formula that weighted the dimensions. Part 2: overall rating of participant's current health used Visual Analog Scale with endpoints labeled 'best imaginable health state' and 'worst imaginable health state'. Change from baseline = score for Cycle/Day minus baseline score.
Time frame: Baseline, every 6 weeks up to end of treatment or early termination (up to Month 33)
Population: ITT population; data not analyzed because study failed its primary endpoint.
Secondary
Change From Baseline in EORTC-QLQ Breast Cancer Module (EORTC-QLQ-BR23) Score
EORTC-QLQ-BR23 measured multi-item functional scales for body image, sexual functioning, sexual enjoyment, and future perspective and measured single item symptoms scales which assessed systemic therapy side effects, breast symptoms, arm symptoms, and upset by hair loss. For functional scales, scores ranged from 0 to 100 where higher scores represented a better level of functioning. For symptoms scales, scores ranged from 0 to 100 where higher scores represented a greater degree of symptoms. Change from baseline = score for Cycle/Day minus baseline score.
Time frame: Baseline, every 6 weeks up to end of treatment or early termination (up to Month 33)
Population: ITT population; data not analyzed because study failed its primary endpoint.
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionaire-C30 (EORTC- QLQ-C30) Score
EORTC QLQ-C30 measured 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnoea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. For functional domains and global health status, scores ranged from 0 to 100 where higher scores represented a better level of functioning. For symptoms scales, scores ranged from 0 to 100 where higher scores represented a greater degree of symptoms. Change from baseline = score for Cycle/Day minus baseline score.
Time frame: Baseline, every 6 weeks up to end of treatment or early termination (up to Month 33)
Population: ITT population; data not analyzed because study failed its primary endpoint.
Secondary
Duration of Response (DR)
DR defined as time from first objective documentation of complete or partial response that was subsequently confirmed to first documentation of disease progression or to death due to any cause, whichever occurred first. DR calculated (Months) = (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4.
Time frame: Baseline up to Month 33
Population: ITT population. Number of participants analyzed = number of participants with confirmed objective tumor response.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Docetaxel + Sunitinib | Duration of Response (DR) | Independent radiology asssessment (n=151, 116) | 7.5 months |
| Docetaxel + Sunitinib | Duration of Response (DR) | Investigator's assessment (n=156, 130) | 6.9 months |
| Docetaxel | Duration of Response (DR) | Independent radiology asssessment (n=151, 116) | 7.2 months |
| Docetaxel | Duration of Response (DR) | Investigator's assessment (n=156, 130) | 5.8 months |
Secondary
Overall Survival (OS)
Time from randomization to date of death due to any cause. OS calculated as (Months) = (death date minus date of first dose of study medication plus 1) divided by 30.4. For participants who were alive, overall survival was censored at last contact.
Time frame: Baseline to date of death from any cause (up to Month 33)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel + Sunitinib | Overall Survival (OS) | 26.0 months |
| Docetaxel | Overall Survival (OS) | 28.9 months |
p-value: 0.893395% CI: [0.9209, 1.4458]Log Rank
Secondary
Percentage of Participants With Objective Response
Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as the disappearance of all tumor lesions (target and non-target). PR defined as greater than or equal to 30 percent (≥30%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions with a non-progressive disease status of the non-target lesions.
Time frame: Baseline up to Month 33
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Docetaxel + Sunitinib | Percentage of Participants With Objective Response | Independent radiology assessment | 51.0 percentage of participants |
| Docetaxel + Sunitinib | Percentage of Participants With Objective Response | Investigator's assessment | 52.7 percentage of participants |
| Docetaxel | Percentage of Participants With Objective Response | Independent radiology assessment | 39.1 percentage of participants |
| Docetaxel | Percentage of Participants With Objective Response | Investigator's assessment | 43.8 percentage of participants |
Comparison: Independent radiology assessmentp-value: 0.001895% CI: [1.17, 2.33]Cochran-Mantel-Haenszel
Comparison: Investigator's assessmentp-value: 0.017295% CI: [1.03, 2.02]Cochran-Mantel-Haenszel