CLEAR-B: Cancer Landscape - Early Adjuvant Retrospective Registry - Breast Cancer
Study Details
Study Description
Brief Summary
This is a non-interventional retrospective cohort study of premenopausal patients with HR+/HER2- breast cancer who are treated in the adjuvant setting with either Tamoxifen, Tamoxifen + Ovarial Function Suppression or Aromatase inhibitor + Ovarial Function Suppression.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
The treatment landscape concerning the adjuvant endocrine therapy in premenopausal patients with early-stage hormone receptor positive (HRpos) breast cancer is quite heterogeneous and therapy recommendations can vary. Tamoxifen (TAM) is a common treatment option that does not require OFS, but research suggests that adding OFS to tamoxifen may improve outcomes. Aromatase inhibitors (AI) are another option, but they can only be used with OFS for premenopausal patients. Studies have shown that AI + OFS improves disease-free survival compared to TAM + OFS, but it may lead to additional side effects such as osteopenia and bone fractures.
The CLEAR-B study aims to provide a detailed description of the therapy landscape in this therapeutic setting, including recurrence rates and overall survival with AI compared to TAM, as well as a comparison of the chosen therapies within prognostic subgroups.
CLEAR-B is a retrospective cohort study, collecting data of premenopausal patients who were diagnosed with early-stage breast cancer between January 2016 and June 2019 in a certified breast cancer center. These patients had an intermediate or high risk of cancer recurrence, as defined by (neo)adjuvant chemotherapy, and/or pT≥2cm at the timepoint of definitive surgery and/or at least one positive lymph node at the time of definite surgery (pN+).
The primary objective is to compare the invasive disease-free survival (iDFS) of patients who were treated with AI + OFS vs. those who were treated with TAM ± OFS. Additionally, the study will compare distant disease-free survival (DDFS) and overall survival (OS) between the two groups and perform subgroup analyses according to risk stratification (stage II and III). This study will be conducted at around 75 certified breast cancer centers and will enroll up to 3000 patients.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| AI+OFS adjuvant treatment with aromatase inhibitor + OFS (ovarian function suppression) |
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| TAM Patients started the adjuvant treatment with Tamoxifen ± OFS |
Outcome Measures
Primary Outcome Measures
- iDFS [First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years]
The primary study aim is to show that aromatase inhibitor (AI) based treatments (AI arm) are not inferior to treatments based on tamoxifen (tamoxifen arm) in terms of invasive diseasefree survival (iDFS). iDFS will be assessed as time to event. Events for iDFS include: Invasive Ipsilateral Breast Tumor Recurrence (IBTR), Local/Regional Invasive Recurrence, Distant Recurrence, Death from BC, Death from Non-BC Cause, Death From unknown cause, Invasive Contralateral BC, Second Primary Invasive Cancer (non-breast)
- Comparison of iDFS [First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years]
In case non-inferiority is confirmed, the superiority of Cohort AI+OFS over Cohort TAM will be tested with regard to iDFS. iDFS will be assessed as time to event. Events for iDFS include: Invasive Ipsilateral Breast Tumor Recurrence (IBTR), Local/Regional Invasive Recurrence, Distant Recurrence, Death from BC, Death from Non-BC Cause, Death From unknown cause, Invasive Contralateral BC, Second Primary Invasive Cancer (non-breast)
Secondary Outcome Measures
- Comparison of DDFS [First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years]
To analyze the non-inferiority of the Cohort AI+OFS compared with the Cohort TAM with regard to distant disease-free survival (DDFS). DDFS will be assessed as time to event. Events for DDFS include distant recurrence, death from breast cancer, death from non-breast cancer cause, death from unknown cause.
- Comparison of OS [First start of adjuvant endocrine therapy until date of death up to 5 years]
To analyze the non-inferiority of the Cohort AI+OFS compared with the Cohort TAM with regard to overall survival (OS). In case non-inferiority is confirmed, the superiority of Cohort AI+OFS over Cohort TAM will be tested with regard to OS. OS is defined as time from first start of adjuvant endocrine therapy until date of death due to any cause.
- Comparison of iDFS in Cohort TAM [First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years]
To compare patients within the Cohort TAM who were treated with OFS and those who were not treated with OFS. iDFS will be assessed as time to event. Events for iDFS include: Invasive Ipsilateral Breast Tumor Recurrence (IBTR), Local/Regional Invasive Recurrence, Distant Recurrence, Death from BC, Death from Non-BC Cause, Death From unknown cause, Invasive Contralateral BC, Second Primary Invasive Cancer (non-breast)
- Comparison of DDFS in Cohort TAM [First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years]
To compare patients within the Cohort TAM who were treated with OFS and those who were not treated with OFS. DDFS will be assessed as time to event. Events for DDFS include distant recurrence, death from breast cancer, death from non-breast cancer cause, death from unknown cause.
- Comparison of OS in Cohort TAM [First start of adjuvant endocrine therapy until date of death up to 5 years]
To compare patients within the Cohort TAM who were treated with OFS and those who were not treated with OFS. OS is defined as time from first start of adjuvant endocrine therapy until date of death due to any cause.
- Comparison of iDFS (TAM+OFS and AI+OFS) [First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years]
To compare patients of Cohort AI+OFS with patients in Cohort TAM, who were treated with OFS with regard to iDFS. iDFS will be assessed as time to event. Events for iDFS include: Invasive Ipsilateral Breast Tumor Recurrence (IBTR), Local/Regional Invasive Recurrence, Distant Recurrence, Death from BC, Death from Non-BC Cause, Death From unknown cause, Invasive Contralateral BC, Second Primary Invasive Cancer (non-breast)
- Comparison of DDFS (TAM+OFS and AI+OFS) [First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years]
To compare patients of Cohort AI+OFS with patients in Cohort TAM, who were treated with OFS with regard to DDFS. DDFS will be assessed as time to event. Events for DDFS include distant recurrence, death from breast cancer, death from non-breast cancer cause, death from unknown cause.
- Comparison of OS (TAM+OFS and AI+OFS) [First start of adjuvant endocrine therapy until date of death up to 5 years]
To compare patients of Cohort AI+OFS with patients in Cohort TAM who were treated with OFS. OS is defined as time from first start of adjuvant endocrine therapy until date of death due to any cause.
- Comparison of iDFS (TAM-OFS and AI+OFS) [First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years]
To compare patients of Cohort AI+OFS with patients in Cohort TAM, who were not treated with OFS with regard to iDFS. iDFS will be assessed as time to event. Events for iDFS include: Invasive Ipsilateral Breast Tumor Recurrence (IBTR), Local/Regional Invasive Recurrence, Distant Recurrence, Death from BC, Death from Non-BC Cause, Death From unknown cause, Invasive Contralateral BC, Second Primary Invasive Cancer (non-breast)
- Comparison of DDFS (TAM-OFS and AI+OFS) [First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years]
To compare patients of Cohort AI+OFS with patients in Cohort TAM, who were not treated with OFS with regard to DDFS. DDFS will be assessed as time to event. Events for DDFS include distant recurrence, death from breast cancer, death from non-breast cancer cause, death from unknown cause.
- Comparison of OS (TAM-OFS and AI+OFS) [First start of adjuvant endocrine therapy until date of death up to 5 years]
To compare patients of Cohort AI+OFS with patients in Cohort TAM who were not treated with OFS. OS is defined as time from first start of adjuvant endocrine therapy until date of death due to any cause.
- Influence of disease stage [Baseline until onset of disease progression or death up to 5 years]
To conduct multivariate analyses to estimate the influence of disease stage on prognosis.
- Risk Factors [Baseline until onset of disease progression or death up to 5 years]
To conduct subgroup analyses for the survival outcomes (iDFS, DDFS, OS) according to risk stratification (stage II and stage III)
- NATALEE Comparison [Baseline until onset of disease progression or death up to 5 years]
To compare patients who are matching the inclusion and exclusion criteria of the pivotal study NATALEE and who were treated in Cohort AI+OFS with patients matching the NATALEE population and who were treated in Cohort TAM.
Other Outcome Measures
- Therapy frequencies [Baseline]
To assess the frequency of the different therapies according to risk groups
- Adherence [End of Treatment/ Treatment termination up to 5 years]
Number of patients with specified reason for therapy termination (recurrence, side effects, patients' wishes etc.)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Female patients with a first primary diagnosis of hormone receptor-positive, HER2- negative unilateral early breast cancer for whom an endocrine treatment is indicated
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Patients must be at least 18 years of age but not older than 60
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Premenopausal defined as all statements must be true
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No oophorectomy before the diagnosis of breast cancer
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Women with uterus: Regular, physiological menses at the timepoint of therapy decision for anti-endocrine treatment in the absence of contraceptives and hormonal treatment
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Women without uterus and remaining ovaries: premenopausal hormone levels must be documented at the time of therapy decision for anti-endocrine treatment
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Patients with an intermediate or high-risk early-stage breast cancer defined as: At least one of the following must be fulfilled
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(Neo)adjuvant chemotherapy
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pT≥2cm at the timepoint of definitive surgery
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at least one positive lymph node at the time of definite surgery (pN+)
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Patient must be previously registered in and must have been documented as part of the certification process for a certified breast cancer center according to the Deutsche Krebsgesellschaft/Deutsche Gesellschaft für Senologie
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Breast Cancer must have been diagnosed between Jan 2016 and Jun 2019
Exclusion Criteria:
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Patients with a low recurrence risk (see inclusion criteria for definition)
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Locally advanced breast cancer or distant metastases at diagnosis
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Male biological sex
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Patients not treated in a certified breast cancer center
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Treatment with CDK4/6Previous diagnosis of invasive breast cancer or in situ breast cancer
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Concurrent invasive malignancy
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Bilateral breast cancer at the timepoint of diagnosis
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Previous diagnosis of invasive breast cancer or in situ breast cancer is not allowed
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Gynecology and Obstetrics, Erlangen University Hospital | Erlangen | Germany | 91054 |
Sponsors and Collaborators
- Institut fuer Frauengesundheit
- AGO Breast Study Group e.V.
- Novartis Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IFG-02-2022
- AGOB-059