Metastatic Breast Cancer
Conditions
Keywords
Metastatic breast cancer, Real world data, Surrogate
Brief summary
Overall survival (OS) is considered the most reliable cancer endpoint and used by the Health Rregulatory authorities (HRA). OS presents multiple advantages in cancer randomized controlled trials (RCT): it is universally accepted as a measure of clinical benefit for the patient; it is objectively defined, both in terms of events and date of incidence; it is easily and precisely measured and thus reproducible; it can be exhaustively collected. As such, OS has been validated by HRAs. On the other hand, OS presents some limitations. Observing a benefit on OS may require a large number of patients and/or considerable time for patient follow-up. Costs for trials may be increased, and there might be delays in the introduction of possible beneficial treatments for patients. The development of alternative endpoints that could capture treatment benefit appropriately and be measurable earlier, is central for the evolution of clinical research in oncology. Real world data (RWD) are defined as other sources than clinical trials such as: electronic medical records, registries, insurance claims, pharmacy records, death certificates and other patient-generated data. This research is aimed at (i) describing the existing endpoints of survival in real-life setting, (ii) comparing the correlation at individual level with data to clinical trials for related to anti-HER2 targeted therapies and endocrine therapies in MBC. We will investigate the individual correlation between candidate surrogate endpoints and overall survival in a population-based record-computerized database centralizing data on about 20,000 patients from 2008 to 2017 in France. This work should lead to the estimation of various time-to event endpoints (e.g. OS, PFS, etc), in the real-life setting, for mBC patients. In addition, we will estimate their individual correlation with OS, which should help us highlight potential surrogate endpoints in this setting. We will focuss on three distinct population, accounting for a large population of mBS patients: : patients treated with anti-HER2 targeted agents, patients treated with endocrine therapies and elderly population.
Interventions
DRUGChemotherapy (exclusive)
Administration of any chemotherapeutic agent(s)
DRUGEndocrine therapy (exclusive)
Administration of any type of endocrine therapy
DRUGCombination of endocrine therapy and chemotherapy
Any combination of endocrine therapy and chemotherapy
DRUGChemotherapy and targeted treatment
Any combination of chemotherapy and targeted treatment(s)
DRUGCombination of endocrine therapy and targeted treatment
Any combination of endocrine therapy and targeted treatment
DRUGCombination of chemotherapy, endocrine therapy and targeted treatment
Any combination of chemotherapy, endocrine therapy and targeted treatment(s)
Sponsors
UNICANCER
Institut du Cancer de Montpellier - Val d'Aurelle
Institut Bergonié
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
ELIGIBILITY * female patients older than 18 years * diagnosis of metastatic breast cancer (de novo disease or first metastatic recurrence) between January 1, 2008, and December 31, 2017 * received a fist-line systemic treatment such as chemotherapy, endocrine therapy or targeted therapy, whatever the sequence (monotherapy or combination of therapies using distinct mechanisms of actions, i.e., polytherapy).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | 10 years | OS was defined as the time from diagnosis of mBC to the date of death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | 10 years | rwPFS was defined as the delay between time from initial diagnosis of mBC to the date of disease progression (regional recurrence, progression, appearance/occurrence of metastases and distant recurrence) or death (any cause), whichever came first. Disease progression was assessed by the treating physician based on observed clinical events, as per routine practice (regional recurrence, progression, appearance/occurrence of metastases and distant recurrence). These events were recorded in the patient medical record. As this study relates to real-world data, no specific procedure was imposed to assess these events. |
| Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | 10 years | Individual-level association between rwPFS and OS estimated using a Spearman rank correlation coefficient. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) Women with a diagnosis of HR+ /HER2- metastatic breast cancer (mBC) and satisfying eligibility criteria | 13,283 |
| Women With a Diagnosis of HR- /HER2- Metastatic Breast Cancer (mBC) Women with a diagnosis of HR- /HER2- metastatic breast cancer (mBC) and satisfying eligibility criteria | 2,845 |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) Women with a diagnosis of HR+ /HER2+ metastatic breast cancer (mBC) and satisfying eligibility criteria | 2,502 |
| Women With a Diagnosis of HR- /HER2+ Metastatic Breast Cancer (mBC) Women with a diagnosis of HR- /HER2+ metastatic breast cancer (mBC) and satisfying eligibility criteria | 1,403 |
| Total | 20,033 |
Baseline characteristics
| Characteristic | Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Women With a Diagnosis of HR- /HER2- Metastatic Breast Cancer (mBC) | Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Women With a Diagnosis of HR- /HER2+ Metastatic Breast Cancer (mBC) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 62 years | 56 years | 57 years | 56 years | 60 years |
| Grade Grade 1 | 1532 Participants | 46 Participants | 132 Participants | 16 Participants | 1726 Participants |
| Grade Grade 2 | 6883 Participants | 758 Participants | 1125 Participants | 459 Participants | 9225 Participants |
| Grade Grade 3 | 2775 Participants | 1662 Participants | 866 Participants | 724 Participants | 6027 Participants |
| Grade Grade not documented | 2093 Participants | 379 Participants | 379 Participants | 204 Participants | 3055 Participants |
| Race and Ethnicity Not Collected | — | — | — | — | 0 Participants |
| Region of Enrollment France | 13283 Participants | 2845 Participants | 2502 Participants | 1403 Participants | 20033 Participants |
| Sex: Female, Male Female | 13283 Participants | 2845 Participants | 2502 Participants | 1403 Participants | 20033 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
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 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies
OS was defined as the time from diagnosis of mBC to the date of death from any cause.
Time frame: 10 years
Population: OS is reported for major combinations of treatments. For the combination of treatments OTHER, OS is not reported given the populations are highly heterogeneous, and therefore reporting OS is not clinically relevant.~When the number of participants in a row is 0, this means that the combinbation of treatments (defined by the row) was provided to 0 woman of the population (defined by the column).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Combination of endocrine therapy and chemotherapy | 48.5 months |
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy and targeted treatment | 27.8 months |
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Endocrine therapy (exclusive) | 48.8 months |
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy (exclusive) | 23.7 months |
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Combination of endocrine therapy and targeted treatment | 58.8 months |
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Combination of chemotherapy, endocrine therapy and targeted treatment | 42.6 months |
| Women With a Diagnosis of HR- /HER2- Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy and targeted treatment | 15.8 months |
| Women With a Diagnosis of HR- /HER2- Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy (exclusive) | 13.5 months |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Combination of chemotherapy, endocrine therapy and targeted treatment | 86.1 months |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy (exclusive) | 30.9 months |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Endocrine therapy (exclusive) | 40.3 months |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Combination of endocrine therapy and chemotherapy | 29.5 months |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy and targeted treatment | 47.6 months |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Combination of endocrine therapy and targeted treatment | 56.3 months |
| Women With a Diagnosis of HR- /HER2+ Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy and targeted treatment | 43.8 months |
| Women With a Diagnosis of HR- /HER2+ Metastatic Breast Cancer (mBC) | Overall Survival (OS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy (exclusive) | 17.4 months |
Secondary
Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies
Individual-level association between rwPFS and OS estimated using a Spearman rank correlation coefficient.
Time frame: 10 years
Population: Individual-level association between rwPFS and OS is reported for major combinations of treatments.~For the combination OTHER, this individual-level association is not reported given the populations are highly heterogeneous, and therefore reporting ondividual-level association is not clinically relevant.~When the number of participants in a row is 0, this means that the combinbation of treatments (defined by the row) was provided to 0 woman of the population (defined by the column).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Chemotherapy (exclusive) | 0.58 Correlation coefficient |
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Endocrine therapy (exclusive) | 0.66 Correlation coefficient |
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Combination of endocrine therapy and chemotherapy | 0.78 Correlation coefficient |
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Chemotherapy and targeted treatment | 0.45 Correlation coefficient |
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Combination of endocrine therapy and targeted treatment | 0.61 Correlation coefficient |
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Combination of chemotherapy, endocrine therapy and targeted treatment | 0.7 Correlation coefficient |
| Women With a Diagnosis of HR- /HER2- Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Chemotherapy (exclusive) | 0.81 Correlation coefficient |
| Women With a Diagnosis of HR- /HER2- Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Chemotherapy and targeted treatment | 0.73 Correlation coefficient |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Combination of endocrine therapy and targeted treatment | 0.71 Correlation coefficient |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Chemotherapy and targeted treatment | 0.67 Correlation coefficient |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Chemotherapy (exclusive) | 0.33 Correlation coefficient |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Endocrine therapy (exclusive) | 0.43 Correlation coefficient |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Combination of endocrine therapy and chemotherapy | 0.72 Correlation coefficient |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Combination of chemotherapy, endocrine therapy and targeted treatment | 0.78 Correlation coefficient |
| Women With a Diagnosis of HR- /HER2+ Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Chemotherapy and targeted treatment | 0.81 Correlation coefficient |
| Women With a Diagnosis of HR- /HER2+ Metastatic Breast Cancer (mBC) | Association Between Overall Survival and Real-world Progression-free Survival for Commonly Prescribed First-line Treatment Strategies | Chemotherapy (exclusive) | 0.67 Correlation coefficient |
Secondary
Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies
rwPFS was defined as the delay between time from initial diagnosis of mBC to the date of disease progression (regional recurrence, progression, appearance/occurrence of metastases and distant recurrence) or death (any cause), whichever came first. Disease progression was assessed by the treating physician based on observed clinical events, as per routine practice (regional recurrence, progression, appearance/occurrence of metastases and distant recurrence). These events were recorded in the patient medical record. As this study relates to real-world data, no specific procedure was imposed to assess these events.
Time frame: 10 years
Population: rwPFS is reported for major combinations of treatments. For the combination of treatments OTHER, rwPFS is not reported given the populations are highly heterogeneous, and therefore reporting rwPFS is not clinically relevant.~When the number of participants in a row is 0, this means that the combinbation of treatments (defined by the row) was provided to 0 woman of the population (defined by the column).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy (exclusive) | 5.0 months |
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Endocrine therapy (exclusive) | 12.5 months |
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Combination of endocrine therapy and chemotherapy | 16.2 months |
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy and targeted treatment | 7.2 months |
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Combination of endocrine therapy and targeted treatment | 19.4 months |
| Women With a Diagnosis of HR+ /HER2- Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Combination of chemotherapy, endocrine therapy and targeted treatment | 14.5 months |
| Women With a Diagnosis of HR- /HER2- Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy (exclusive) | 5.4 months |
| Women With a Diagnosis of HR- /HER2- Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy and targeted treatment | 6.5 months |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Combination of endocrine therapy and targeted treatment | 12.2 months |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy and targeted treatment | 9.9 months |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy (exclusive) | 4.4 months |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Endocrine therapy (exclusive) | 5.9 months |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Combination of endocrine therapy and chemotherapy | 9.3 months |
| Women With a Diagnosis of HR+ /HER2+ Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Combination of chemotherapy, endocrine therapy and targeted treatment | 24.6 months |
| Women With a Diagnosis of HR- /HER2+ Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy and targeted treatment | 12.3 months |
| Women With a Diagnosis of HR- /HER2+ Metastatic Breast Cancer (mBC) | Real-world Progression-free Survival (rwPFS) for Commonly Prescribed First-line Treatment Strategies | Chemotherapy (exclusive) | 4.4 months |