Breast Cancer
Conditions
Brief summary
This multicenter, observational, prospective study will identify a powerful and easy predictive/prognostic marker to use with participants under bevacizumab.
Interventions
DRUGBevacizumab
Bevacizumab will be administered as per local clinical practice and local labeling.
DRUGPaclitaxel
Paclitaxel will be administered as per local clinical practice and local labeling.
Sponsors
Hoffmann-La Roche
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with HER2-negative metastatic breast cancer. Mandatory to have the HER2/estrogen receptor (ER)/progesterone receptor (PR) status * Participant who met criteria for first-line treatment with chemotherapy plus bevacizumab (standard doses) by local, regional or national guidelines or authorities * Participants with measurable disease (RECIST criteria v1.1) or participants with no measurable but assessable disease * Molecular phenotype as triple negative metastatic breast cancer; and ER-positive tumors need to fulfill at least one of the two clinical criteria: metastatic relapse on adjuvant endocrine therapy or progression to at least one prior line of endocrine therapy for advanced disease; or aggressive disease criteria (at least two criteria): taxane based regimen in the (neo) adjuvant setting; metastatic relapse within 2 years from the end of chemotherapy for early breast cancer; liver metastasis; three or more organs with metastatic involvement; symptomatic visceral disease * Eastern Cooperative Oncology Group (ECOG) 0-2
Exclusion criteria
* Participant has received prior chemotherapy for metastatic disease * Participant requiring major/minor surgery within 3 weeks prior to administration of the first dose of study treatment * Participant has received an investigational therapy within 4 weeks prior to study entry * Participant has known symptomatic brain metastases * Participant with non-measurable or assessable disease: exclusive blastic bone disease; pleural, pericardial or abdominal effusion as only evidence of disease * Participant in chronic daily treatment with corticosteroids (doses greater than \[\>\]10 milligrams per day \[mg/day\] of methylprednisolone or equivalent), except inhaled steroids * Pregnant or breastfeeding participant * Women of childbearing potential who are not using hormonal contraceptives or highly effective birth control during the study * Participant has an active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy * Participant with significant renal, hematological or liver function alteration according to investigator's criteria * Participant has serious medical risk factors involving any of the major organ systems
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Benefit | During follow-up (up to 18 months) | Clinical benefit was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). Clinical benefit is defined as partial or complete response as well as tumor stabilization for up to 24 weeks. Results for clinical benefit were reported for 2 groups based on Circulating Tumor Cells (CTC) Levels. The Sensitive group had CTC levels \<5 (\<5 CTCs in one of the two determinations) and Resistant group had CTC ≥5 (≥ 5 CTCs in the two determinations). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) as Assessed Using RECIST v1.1 | From Baseline up to end of study (up to 18 months) | PFS was evaluated for the Sensitive group (CTC \<5) and Resistant group (CTC ≥5). |
| Overall Survival | From Baseline up to end of study (up to 18 months) | OS was evaluated for the Sensitive group (CTC \<5) and Resistant group (CTC ≥5). |
| Percentage of Participants With Adverse Events of Toxicity Grading 3 and/or 4 | From Baseline up to end of study (up to 18 months) | Adverse events (AEs) will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v 4.0). Any AEs that are not specifically listed in the NCI CTCAE follow the logic - Grade 3) Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4: Life-threatening consequences or urgent intervention indicated. |
| Optimal Cut-off for Clinical Benefit | Baseline (within 21 days prior to Day 1 Cycle 1), 7 days prior to Day 1 Cycle 3 (Cycle length = 28 days) | Clinical benefit was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). Clinical benefit is defined as partial or complete response as well as tumor stabilization for up to 24 weeks. The optimal cut-off for clinical benefit was calculated from a Receiver Operating Curve (ROC) based on CTC level and used to define the prognostic factors that could better predict clinical outcomes. |
| Percentage of Participants With Overall Response as Assessed Using RECIST v1.1 | From Baseline up to end of study (up to 18 months) | Overall response = Complete Response (CR) + Partial Response (PR). Overall response was evaluated for the Sensitive group (CTC \<5) and Resistant group (CTC ≥5). |
| PFS as Assessed Using RECIST v1. in Prognostic Groups | From Baseline up to end of study (up to 18 months) | An optimal cut-off point for the CTC count of 0.5 after 2 cycles of treatment was used to define the prognostic groups. |
| Mean CTC Count Levels | Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days]) | CTC and CEA levels were compared to determine any correlation between the two. Both CTC count at baseline and at cycle 2 were considered. |
| Mean Carcinoembryonic Antigen (CEA) Levels | Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days]) | — |
| Mean Biomarker Cancer Antigen 15.3 (CA 15.3) Level | Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days]) | CTC and CA 15.3 levels were compared to determine any correlation between the two. Both CTC count at baseline and at cycle 2 were considered. |
| Percentage of Participants With Overall Response (OR) as Assessed Using RECIST v1. in Prognostic Groups | Baseline (within 21 days prior to Day 1 Cycle 1), 7 days prior to Day 1 Cycle 3 (Cycle length = 28 days) | Overall response = CR + PR. An optimal cut-off point for the CTC count of 0.5 after 2 cycles of treatment was used to define the prognostic groups. |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants With Metastatic Breast Cancer Participants with metastatic breast cancer receiving bevacizumab in combination with paclitaxel, will be observed for treatment responses for up to 18 months from the start of treatment. | 111 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Change of address | 2 |
| Overall Study | Death | 37 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Participants With Metastatic Breast Cancer |
|---|---|
| Age, Continuous | 54.2 years STANDARD_DEVIATION 11.8 |
| Race/Ethnicity, Customized Race : Arab | 1 participants |
| Race/Ethnicity, Customized Race : Black | 1 participants |
| Race/Ethnicity, Customized Race : Caucasian | 105 participants |
| Race/Ethnicity, Customized Race : Latino | 4 participants |
| Sex: Female, Male Female | 110 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 37 / 111 |
| other Total, other adverse events | 107 / 111 |
| serious Total, serious adverse events | 37 / 111 |
Outcome results
Primary
Percentage of Participants With Clinical Benefit
Clinical benefit was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). Clinical benefit is defined as partial or complete response as well as tumor stabilization for up to 24 weeks. Results for clinical benefit were reported for 2 groups based on Circulating Tumor Cells (CTC) Levels. The Sensitive group had CTC levels \<5 (\<5 CTCs in one of the two determinations) and Resistant group had CTC ≥5 (≥ 5 CTCs in the two determinations).
Time frame: During follow-up (up to 18 months)
Population: Included participants that were evaluable for CTC level after cycle 2.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Participants With Metastatic Breast Cancer | Percentage of Participants With Clinical Benefit | Sensitive | Benefit = Yes | 53 Participants |
| Participants With Metastatic Breast Cancer | Percentage of Participants With Clinical Benefit | Sensitive | Benefit = No | 20 Participants |
| Participants With Metastatic Breast Cancer | Percentage of Participants With Clinical Benefit | Resistant | Benefit = Yes | 5 Participants |
| Participants With Metastatic Breast Cancer | Percentage of Participants With Clinical Benefit | Resistant | Benefit = No | 7 Participants |
Secondary
Mean Biomarker Cancer Antigen 15.3 (CA 15.3) Level
CTC and CA 15.3 levels were compared to determine any correlation between the two. Both CTC count at baseline and at cycle 2 were considered.
Time frame: Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days])
Population: Only included participants that had available data of CA 15.3 levels at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Metastatic Breast Cancer | Mean Biomarker Cancer Antigen 15.3 (CA 15.3) Level | 277.8 U/ml | Standard Deviation 431.3 |
Comparison: Correlation between CTC and CA 15.3 level considering baseline CTC countp-value: <0.001Spearman's correlation analysis
Comparison: Correlation between CTC and CA 15.3 level considering CTC count at cycle 2p-value: 0.241Spearman's correlation analysis
Secondary
Mean Carcinoembryonic Antigen (CEA) Levels
Time frame: Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days])
Population: Only included participants that had available data of CEA levels at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants With Metastatic Breast Cancer | Mean Carcinoembryonic Antigen (CEA) Levels | 46.5 U/ml | Standard Deviation 146.2 |
Secondary
Mean CTC Count Levels
CTC and CEA levels were compared to determine any correlation between the two. Both CTC count at baseline and at cycle 2 were considered.
Time frame: Baseline (within 21 days prior to Day 1 Cycle 1 [Cycle length = 28 days])
Population: Only included participants that had available data of CTC levels at baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Metastatic Breast Cancer | Mean CTC Count Levels | CTC (baseline CTC) | 91.6 count/7.5 ml (CTC) | Standard Deviation 355.5 |
| Participants With Metastatic Breast Cancer | Mean CTC Count Levels | CTC (cycle 2 CTC) | 3.9 count/7.5 ml (CTC) | Standard Deviation 10.8 |
Comparison: Correlation between CTC and CEA level considering baseline CTC countp-value: <0.001Spearman's correlation analysis
Comparison: Correlation between CTC and CEA level considering CTC count at cycle 2p-value: 0.444Spearman's correlation analysis
Secondary
Optimal Cut-off for Clinical Benefit
Clinical benefit was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). Clinical benefit is defined as partial or complete response as well as tumor stabilization for up to 24 weeks. The optimal cut-off for clinical benefit was calculated from a Receiver Operating Curve (ROC) based on CTC level and used to define the prognostic factors that could better predict clinical outcomes.
Time frame: Baseline (within 21 days prior to Day 1 Cycle 1), 7 days prior to Day 1 Cycle 3 (Cycle length = 28 days)
Population: Included only participants that were evaluable for CTC level after cycle 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Metastatic Breast Cancer | Optimal Cut-off for Clinical Benefit | 0.5 cells/7.5 ml |
Secondary
Overall Survival
OS was evaluated for the Sensitive group (CTC \<5) and Resistant group (CTC ≥5).
Time frame: From Baseline up to end of study (up to 18 months)
Population: Included only participants that were evaluable for CTC level after cycle 2.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Participants With Metastatic Breast Cancer | Overall Survival | Sensitive | NA months |
| Participants With Metastatic Breast Cancer | Overall Survival | Resistant | 13.01 months |
Secondary
Percentage of Participants With Adverse Events of Toxicity Grading 3 and/or 4
Adverse events (AEs) will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v 4.0). Any AEs that are not specifically listed in the NCI CTCAE follow the logic - Grade 3) Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4: Life-threatening consequences or urgent intervention indicated.
Time frame: From Baseline up to end of study (up to 18 months)
Population: Included only participants that were evaluable for CTC level after cycle 2.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Participants With Metastatic Breast Cancer | Percentage of Participants With Adverse Events of Toxicity Grading 3 and/or 4 | Sensitive | Grade 3-4 toxicity = yes | 28 Participants |
| Participants With Metastatic Breast Cancer | Percentage of Participants With Adverse Events of Toxicity Grading 3 and/or 4 | Sensitive | Grade 3-4 toxicity = no | 45 Participants |
| Participants With Metastatic Breast Cancer | Percentage of Participants With Adverse Events of Toxicity Grading 3 and/or 4 | Resistant | Grade 3-4 toxicity = yes | 6 Participants |
| Participants With Metastatic Breast Cancer | Percentage of Participants With Adverse Events of Toxicity Grading 3 and/or 4 | Resistant | Grade 3-4 toxicity = no | 6 Participants |
Secondary
Percentage of Participants With Overall Response as Assessed Using RECIST v1.1
Overall response = Complete Response (CR) + Partial Response (PR). Overall response was evaluated for the Sensitive group (CTC \<5) and Resistant group (CTC ≥5).
Time frame: From Baseline up to end of study (up to 18 months)
Population: Included participants that were evaluable for CTC level after cycle 2.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Participants With Metastatic Breast Cancer | Percentage of Participants With Overall Response as Assessed Using RECIST v1.1 | Sensitive | Overall Response = Yes | 35 Participants |
| Participants With Metastatic Breast Cancer | Percentage of Participants With Overall Response as Assessed Using RECIST v1.1 | Sensitive | Overall Response = No | 38 Participants |
| Participants With Metastatic Breast Cancer | Percentage of Participants With Overall Response as Assessed Using RECIST v1.1 | Resistant | Overall Response = Yes | 2 Participants |
| Participants With Metastatic Breast Cancer | Percentage of Participants With Overall Response as Assessed Using RECIST v1.1 | Resistant | Overall Response = No | 10 Participants |
Secondary
Percentage of Participants With Overall Response (OR) as Assessed Using RECIST v1. in Prognostic Groups
Overall response = CR + PR. An optimal cut-off point for the CTC count of 0.5 after 2 cycles of treatment was used to define the prognostic groups.
Time frame: Baseline (within 21 days prior to Day 1 Cycle 1), 7 days prior to Day 1 Cycle 3 (Cycle length = 28 days)
Population: Included only participants that were evaluable for CTC level after cycle 2.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Participants With Metastatic Breast Cancer | Percentage of Participants With Overall Response (OR) as Assessed Using RECIST v1. in Prognostic Groups | CTC >0.5 | Overall Response = Yes | 14 Participants |
| Participants With Metastatic Breast Cancer | Percentage of Participants With Overall Response (OR) as Assessed Using RECIST v1. in Prognostic Groups | CTC >0.5 | Overall Response = No | 27 Participants |
| Participants With Metastatic Breast Cancer | Percentage of Participants With Overall Response (OR) as Assessed Using RECIST v1. in Prognostic Groups | CTC ≤0.5 | Overall Response = Yes | 23 Participants |
| Participants With Metastatic Breast Cancer | Percentage of Participants With Overall Response (OR) as Assessed Using RECIST v1. in Prognostic Groups | CTC ≤0.5 | Overall Response = No | 21 Participants |
Secondary
PFS as Assessed Using RECIST v1. in Prognostic Groups
An optimal cut-off point for the CTC count of 0.5 after 2 cycles of treatment was used to define the prognostic groups.
Time frame: From Baseline up to end of study (up to 18 months)
Population: Included only participants that were evaluable for CTC level after cycle 2.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Participants With Metastatic Breast Cancer | PFS as Assessed Using RECIST v1. in Prognostic Groups | CTC <0.5 | 22.60 months |
| Participants With Metastatic Breast Cancer | PFS as Assessed Using RECIST v1. in Prognostic Groups | CTC ≥0.5 | 8.05 months |
Secondary
Progression Free Survival (PFS) as Assessed Using RECIST v1.1
PFS was evaluated for the Sensitive group (CTC \<5) and Resistant group (CTC ≥5).
Time frame: From Baseline up to end of study (up to 18 months)
Population: Included participants that were evaluable for CTC level after cycle 2.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Participants With Metastatic Breast Cancer | Progression Free Survival (PFS) as Assessed Using RECIST v1.1 | Sensitive | 17.38 months |
| Participants With Metastatic Breast Cancer | Progression Free Survival (PFS) as Assessed Using RECIST v1.1 | Resistant | 5.49 months |