Circulating Tumor Cells, Synchronous Metastasized Breast Cancer
Conditions
Keywords
breast cancer, ABCSG, POSYTIVE, growth factor, median survival, surgery on demand, surgical therapy, blood specimen, tissue specimen, VEGF, TGF, circulating tumor cells, stem cells
Brief summary
Primary Operation in synchronous metastasized invasive breast cancer to evaluate the use of local therapy
Detailed description
This study is a prospective, randomized, multicentre, study concerning the influence of local treatment on the patients with synchronous metastasized breast cancer. Patients will be stratified at inclusion according to the centre, the menopausal status (pre-menopausal, post-menopausal), the hormone-receptor status (ER-/PR-/not determinable; any PR and/or Er+), the HER-2 status (positive vs. negative/not determinable), the grading (G1/G2/not determinable vs. G3), location of metastases (visceral ± vs bone only), organs with metastases (single organ vs multiple organs) and use of first line chemotherapy (anthracycline ± vs. taxane vs others). Thereafter patients will be randomly assigned to receive either local therapy of the breast (lumpectomy or mastectomy + axillary surgery /± radiotherapy) versus no local therapy. Systemic therapy will be administered at the centers policy.
Interventions
PROCEDURESurgery
lumpectomy or mastectomy with or without radiotherapy. Sentinel biopsy followed by axillary dissection (level I-II)
PROCEDURESurgery on Demand
if necessary local therapy on demand
Sponsors
Bayer
Amgen
Hoffmann-La Roche
AstraZeneca
Sanofi
Wyeth-Lederle Pharma GmbH
GlaxoSmithKline
Merck Sharp & Dohme LLC
Fond of the Viennese Mayor
Austrian Breast & Colorectal Cancer Study Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients age ≥ 18 years * Eastern Cooperative Oncology Group Performance Status is 0 -2 * Untreated synchronous metastasized invasive carcinoma of the breast with the primary tumor in situ (bilateral synchronous metastasized breast cancer patients are eligible) * The primary tumor must be identified and may be any size, however, primary resection with resection free margins must be possible * Invasive adenocarcinoma of the breast on histological examination * The metastatic site must be identified by radiological assessment(Computer Tomography of the chest and the abdomen OR ultrasound and chest x ray for visceral metastases; bone scan AND/OR computer tomography AND/OR magnetic resonance for bone metastases). A biopsy is not necessary. * Written informed consent must be obtained and documented prior to beginning any protocol specific procedures and according to local regulatory requirements * able to comply with the protocol requirements during the treatment and follow-up period.
Exclusion criteria
* Patients in whom a R0 resection (microscopic free margins) is clinically questionable * Inflammatory cancer * Patients with a brain metastasis * Patients who are not eligible for general anesthesia and operations * Patients without metastatic breast cancer (patients with a tumor marker value (CEA, CA15-3) above normal levels without the radiological proven evidence of metastases are not eligible for the study) * Patients with a second untreated malignancy * Any previous malignancy treated with curative intent and the patient has not been disease-free for 5 years - exceptions are: (a)carcinoma in situ of the cervix, (b)squamous carcinoma of the skin, (c)basal cell carcinoma of the skin * Patients with any recurrent cancer disease * Pregnant or lactating women * Patients are not allowed to be part of another local therapy trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Time from randomization until the last visit of the last participant; maximum time on study was 63.9 months | Overall Survival with vs without local therapy (surgery) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Distant Progression | Time from randomization until the last visit of the last participant; maximum time on study was 63.9 months | Time to distant progression with vs without local therapy (surgery) |
| Time to Local Progression (TTPl) | Time from randomization until the last visit of the last participant; maximum time on study was 63.9 months | Time to local progression with vs without local therapy (surgery) |
Countries
Austria
Participant flow
Recruitment details
The first patient was randomized November 24, 2010, the last patient was randomized October 30, 2015. Randomization took place in 14 Austrian clinical sites. In total, 90 patients were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| A: Surgical Therapy Local therapy consists of lumpectomy or mastectomy with or without radiotherapy (according to center tumor board decision) with a resection free margin of at least 1 mm or more demonstrated on paraffin embedded histological sections. Intraoperative frozen sections are allowed but not definitive for margin assessment. Sentinel node biopsy may be performed and has always to be followed by axillary dissection of level I and II (axillary surgery level I and II is mandatory).
Surgery: lumpectomy or mastectomy with or without radiotherapy. Sentinel biopsy followed by axillary dissection (level I-II) | 45 |
| B: Surgery on Demand In Arm B (no local therapy) it may be necessary to perform local therapy on demand (surgery, radiotherapy). Reasons may be uncontrolled bleeding or infected exulcerations with a septic component and no treatment benefit from conservative therapy. This will be considered as protocol deviation. However, the patient's follow up is recorded and data are available for analyses as intention to treat.
Surgery on Demand: if necessary local therapy on demand | 45 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 30 | 22 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | A: Surgical Therapy | B: Surgery on Demand | Total |
|---|---|---|---|
| Age, Continuous | 62 years | 65 years | 64 years |
| HER2 group FISH amplified/IHC+++ | 10 Participants | 8 Participants | 18 Participants |
| HER2 group Negative | 35 Participants | 36 Participants | 71 Participants |
| HER2 group Unknown | 0 Participants | 1 Participants | 1 Participants |
| Histologic grade G1 | 5 Participants | 2 Participants | 7 Participants |
| Histologic grade G2 | 23 Participants | 25 Participants | 48 Participants |
| Histologic grade G3 | 13 Participants | 15 Participants | 28 Participants |
| Histologic grade Gx | 3 Participants | 1 Participants | 4 Participants |
| Histologic grade Unknown | 1 Participants | 2 Participants | 3 Participants |
| Hormone receptor group Any positive | 36 Participants | 37 Participants | 73 Participants |
| Hormone receptor group Estrogen and Progesterone negative | 9 Participants | 8 Participants | 17 Participants |
| N-stage cN0 | 10 Participants | 10 Participants | 20 Participants |
| N-stage cN1 | 20 Participants | 21 Participants | 41 Participants |
| N-stage cN2 | 7 Participants | 2 Participants | 9 Participants |
| N-stage cN3 | 4 Participants | 2 Participants | 6 Participants |
| N-stage Unknown | 4 Participants | 10 Participants | 14 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 45 Participants | 45 Participants | 90 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Surgery type Breast-conserving | 12 Participants | 3 Participants | 15 Participants |
| Surgery type Missing | 3 Participants | 38 Participants | 41 Participants |
| Surgery type Modified radical | 30 Participants | 4 Participants | 34 Participants |
| T-stage cT1 | 11 Participants | 7 Participants | 18 Participants |
| T-stage cT2 | 14 Participants | 26 Participants | 40 Participants |
| T-stage cT3 | 10 Participants | 3 Participants | 13 Participants |
| T-stage cT4 | 8 Participants | 8 Participants | 16 Participants |
| T-stage Unkown | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 30 / 45 | 22 / 45 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Overall Survival (OS)
Overall Survival with vs without local therapy (surgery)
Time frame: Time from randomization until the last visit of the last participant; maximum time on study was 63.9 months
Population: Intent-to-treat population: All participants assigned to one of the two treatment arms were included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A: Surgical Therapy | Overall Survival (OS) | 34.6 months |
| B: Surgery on Demand | Overall Survival (OS) | 56.2 months |
Comparison: To determine the effect of local therapy (surgery, Arm A) compared to systemic therapy only (Arm B) in synchronous metastasized breast cancer patients in terms of overall survival. Overall survival is defined as the time from randomization to death from any cause. Participants last known to be alive were censored at their last contact date or at the data cut-off date whichever came first.p-value: 0.04295% CI: [1.01, 3.09]Log Rank
Secondary
Time to Distant Progression
Time to distant progression with vs without local therapy (surgery)
Time frame: Time from randomization until the last visit of the last participant; maximum time on study was 63.9 months
Population: Intent-to-treat population: All participants assigned to one of the two treatment arms were included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A: Surgical Therapy | Time to Distant Progression | 13.7 months |
| B: Surgery on Demand | Time to Distant Progression | 24.4 months |
Comparison: To determine the effect of local therapy (surgery) compared to systemic therapy only in synchronous metastasized breast cancer patients in terms of time from randomization to distant progression. Distant progression is defined as detection of new lesions or progression of existing metastases in locations different then breast. Participants last known to be alive without a distant progression were censored at their last contact date or at the data cut-off date whichever came first.p-value: 0.14795% CI: [0.87, 2.42]Log Rank
Secondary
Time to Local Progression (TTPl)
Time to local progression with vs without local therapy (surgery)
Time frame: Time from randomization until the last visit of the last participant; maximum time on study was 63.9 months
Population: Intent-to-treat population: All participants assigned to one of the two treatment arms were included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A: Surgical Therapy | Time to Local Progression (TTPl) | 59.4 months |
| B: Surgery on Demand | Time to Local Progression (TTPl) | 55.8 months |
Comparison: To determine the effect of local therapy (surgery) compared to systemic therapy only in synchronous metastasized breast cancer patients in terms of time from randomization to local progression. Local progression is defined as recurrence in breast with localization mamma, chest wall or axilla. Participants last known to be alive, who did not experience a local progression were censored at their last contact date or at the data cut-off date whichever came first.p-value: 0.8995% CI: [0.45, 2.02]Log Rank