HR+/HER2- aBC Undergoing 1L Treatment With CDK4/6i (Palbociclib, Abemaciclib or Ribociclib) and AI (Anastrozole or Letrozole)
Conditions
Brief summary
Many patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer in the first therapy line is endocrine sensitive. For these patients the established 1st line standard therapy is a combination of a CDK4/6 inhibitor and an aromatase inhibitor. This combination therapy is usually given until clinical progression. Recent studies suggest that a detection of a somatic ESR1 mutation in the ctDNA can be clinically used to prompt an earlier change from the aromatase inhibitor to a selective estrogen receptor degrader. For implementation in the clinical routine it is important to gain knowledge about the dynamics of ESR1 mutation in HR+/HER2- advanced breast cancer patients during their first line therapy. At the beginning of the first line therapy about 5-8% of patients show an ESR1 mutation. An identification of patients with resistance to aromatase inhibitors at that timepoint might not be feasible and cost-efficient. At the timepoint of clinical progression up to 30-40% of patients will have acquired an ESR1 mutation. Knowledge about the mutation frequencies at different timepoints will be very helpful to direct testing strategies for implementing testing broadly in a population. The aim of this study is to test ESR1 mutation frequencies in groups of patients (single time test per patient) with no clinical progression and different durations under first-line treatment with aromatase inhibitor and CDK4/4 inhibitor.
Interventions
DIAGNOSTIC_TESTESR1 testing
Study procedures comprise of a blood sample for ESR1 mutation testing and blood samples for translational research. ESR1 test results from a central testing facility are communicated back to the study site. Treatment of patients will continue as per discretion of the treating physician and will be documented during a single timepoint 3 months post inclusion.
Sponsors
Institut fuer Frauengesundheit
AGO Breast (Arbeitsgemeinschaft Gynäkologische Onkologie)
data4treat GmbH
BioMedStatistics GmbH
ClinSol GmbH & Co KG
Universitätsklinikum Erlangen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject must be female or male and aged ≥ 18 years on the day of signing informed consent 2. Patient has locally advanced or metastatic breast cancer not amenable to curative treatment 3. Patient has HER2- breast cancer confirmed by local laboratory, defined as a negative in situ hybridization test or an IHC status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required to confirm the HER2-negative status (based on the most recently analyzed tissue sample tested by a local laboratory) 4. Histologically confirmed ER-positive and/ or PgR-positive breast cancer determined by core biopsy according to local in-house standard 5. Patient has already initiated or is about to initiate first-line therapy with a CDK4/6 inhibitor (any CDK4/6i) in combination with an aromatase inhibitor (non-steroidal AI). Treatment must be intended as first-line systemic therapy for advanced or metastatic disease 6. Information about prior oncological therapies against the HR+/HER2- BC must be available 7. Data about histo-pathological report must be available, including hormone receptor status, tumor histology, tumor grading and HER2 immunohistochemistry 8. Inclusion in the study occurs as a single, one-time event for each patient, within one of the 9 defined cohorts
Exclusion criteria
1. Patients with an interruption of ongoing first-line CDK4/6i plus AI therapy exceeding 1 month for either CDK4/6i or AI 2. Patients receiving any other systemic anticancer therapy for HR+/HER2- aBC, except for LHRH agonists, bisphosphonates, or denosumab 3. Clinical evidence of progression at the timepoint of study inclusion 4. Patients have already completed ≥ 1L of systemic therapy for aBC
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PO1 | Day 1 | mutation frequency of ESR1 mutations as assessed in blood sample |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SO1 | Day 1 | ESR1 mutation frequencies according to age and BMI |
| SO2 | Day 1 | ESR1 mutation frequencies according to type of CDK4/6i therapy |
| SO3 | Day 1 | ESR1 mutation frequencies according to type of aromatase inhibitor |
| SO4 | Day 1 | ESR1 mutation frequencies according to HER2 status (HER2 0, HER2 ultralow, HER2 low) |
| SO5 | Day 1 | ESR1 mutation frequencies according to extent of estrogen and progesterone receptor expression |
| SO6 | Day 1 | ESR1 mutation frequencies according to tumor grading |
| SO7 | Day 1 | ESR1 mutation frequencies according to previous therapies (de novo patients vs. previous adjuvant therapy) |
Countries
Germany
Contacts
CONTACTSponsor's study office
STUDY_DIRECTORPeter Andreas Fasching, Prof. Dr.
AGO-B e.V. c/o Frauenklinik des Universitätsklinikums Erlangen
STUDY_CHAIRVolkmar Müller, Prof. Dr.
Universitätsklinikum Hamburg-Eppendorf; Klinik und Poliklinik für Gynäkologie
STUDY_CHAIRTanja Fehm, Prof. Dr.
Frauenklinik des Universitätsklinikums Düsseldorf
Outcome results
None listed