Advanced Breast Cancer
Conditions
Brief summary
This is a multicountry, multicenter, observational study in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer receiving first-line endocrine-based therapy with an aromatase inhibitor in combination with a CDK4/6 inhibitor. The study aims to describe the prevalence of ESR1 mutations at baseline and the emergence of ESR1 mutations over time using circulating tumor DNA testing in routine clinical practice. Patients receiving first-line treatment for at least 6 months and no more than 18 months, without evidence of disease progression at study entry, may undergo baseline ESR1 mutation testing. Patients with a negative baseline result may undergo longitudinal monitoring approximately every 3 months, for up to 18 months or 6 testing timepoints, to assess emergence of ESR1 mutations. The study will also describe mutation subtypes, testing methods used in routine practice, selected clinical characteristics, and treatment patterns across participating countries.
Detailed description
This is a multicountry, multicenter, observational study designed to determine the prevalence of ESR1 mutations at baseline and to assess the emergence of ESR1 mutations during longitudinal surveillance in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- aBC) receiving first-line treatment with an aromatase inhibitor (AI) in combination with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. Eligible patients are adults with histologically or cytologically confirmed HR+/HER2- advanced breast cancer who have been receiving first-line AI plus CDK4/6 inhibitor therapy for at least 6 months and no more than 18 months, without evidence of disease progression according to investigator assessment, and who are willing and able to provide blood samples for circulating tumor DNA (ctDNA) testing at predefined intervals. Following informed consent, baseline data will be collected in electronic case report forms and will include sociodemographic characteristics, clinical and tumor history, testing methods, and treatment patterns. A baseline blood sample will be collected for ctDNA-based ESR1 mutation testing using testing methods applied in routine clinical practice, including but not limited to quantitative polymerase chain reaction (qPCR), digital polymerase chain reaction (dPCR), and next-generation sequencing (NGS), according to local availability and site capability. Testing will be performed in validated laboratories in accordance with local standard operating procedures. Patients who are negative for ESR1 mutation at baseline will undergo longitudinal ctDNA monitoring approximately every 12 weeks (+/-4 weeks), for up to 18 months or 6 testing time points from initial testing, whichever occurs first. Patients who test positive for ESR1 mutation at baseline or during follow-up will discontinue further study surveillance and will continue to receive routine clinical care as determined by the treating physician. The date of first ESR1 mutation detection will be recorded. The primary objectives are to determine the prevalence of ESR1 mutations at baseline and the emergence rate and time to emergence of ESR1 mutations during the surveillance period among patients who are ESR1 negative at initial testing. Secondary objectives include assessment of ESR1 mutation frequency by duration of first-line therapy and by testing method, distribution of specific ESR1 mutation subtypes, co-mutations with other clinically relevant biomarkers when available, patient clinical and sociodemographic characteristics, testing and treatment patterns, and associations between ESR1 mutation status and relevant patient or treatment factors. Approximately 3,000 patients are planned to be enrolled at about 30 sites in 15 countries across Asia, Latin America, and the Middle East and Africa. The estimated recruitment period is 12 months.
Interventions
OTHERBlood sampling
Blood sampling for ctDNA-based ESR1 mutation testing, which are associated with minimal additional risk and burden compared with routine clinical practice
Sponsors
AstraZeneca
Food and Drug Administration (FDA)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older at the time of informed consent and willing and able to provide informed consent before any study-related procedures. * Histologically- or cytologically-confirmed hormone receptor-positive (ER- and/or progesterone receptor-positive), human epidermal growth factor receptor 2-negative (HER2-negative) advanced breast cancer. * Receiving first-line therapy with an aromatase inhibitor in combination with a CDK4/6 inhibitor for at least 6 months and no more than 18 months, with no evidence of disease progression at study entry, as assessed by the investigator. * Able and willing to provide a blood sample for circulating tumour DNA testing for ESR1 mutation assessment at approximately quarterly intervals.
Exclusion criteria
* Evidence of disease progression during first-line aromatase inhibitor plus CDK4/6 inhibitor therapy, based on investigator assessment. * Known ESR1 mutation status at study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of ESR1 mutations in circulating tumour DNA | At baseline, approximately 3, 6, 9, 12, 15, and 18 months after initial testing | Number and proportion of patients with at least one ESR1 mutation |
| Emergence of ESR1 mutations during longitudinal ctDNA surveillance | At approximately 3, 6, 9, 12, 15, and 18 months after initial testing | Number and proportion of patients who are detected with ESR1 mutation |
| Time to first detection of an ESR1 mutation | From first-line AI plus CDK4/6 inhibitor initiation to first ESR1 mutation detection | Time in months from initiation of first-line treatment with AI and CDK4/6 inhibitors to first detection of ESR1mutation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of ESR1 mutations by duration of ongoing first-line AI plus CDK4/6 inhibitor therapy | At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing | Number and proportion of participants with ESR1 mutations by duration of ongoing first-line therapy with an aromatase inhibitor plus a CDK4/6 inhibitor |
| Frequency of ESR1 mutation-positive results by testing method | At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing | Number and proportion of participants with ESR1 mutation-positive results according to the circulating tumour DNA testing method used. |
| Distribution of ESR1 mutation subtypes and allele frequency | At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing | Number and proportion of participants with specific ESR1 mutation subtypes detected by circulating tumour DNA testing. |
| Frequency of additional co-mutations among ESR1 mutation-positive participants | At baseline and approximately every 3 months through study completion, up to approximately 18 months after initial ESR1 testing | Number and proportion of participants with ESR1 mutations who have at least 1 additional clinically relevant co-mutation detected, where available. |
| Baseline and follow-up characteristics of the study population | At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing | Summary of selected sociodemographic, clinical, tumour, and testing characteristics of the study population. |
| Relationship between ESR1 mutation status and selected participant and treatment characteristics | At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing | Assessment of the relationship between ESR1 mutation status and selected participant, disease, testing, and treatment characteristics. |
| Treatment patterns for advanced breast cancer | From enrolment through study completion, up to approximately 18 months after initial ESR1 testing | Summary of first-line treatment regimens for advanced breast cancer, including endocrine therapy and CDK4/6 inhibitor use, and duration of therapy. |
| Prior treatment patterns for early-stage breast cancer | At baseline | Summary of prior therapies received for early-stage breast cancer in participants who later developed advanced breast cancer, including duration of therapy and reasons for discontinuation, where available. |
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed