Clinical trial NCT06650423: Adherence to Aromatase Inhibitors ± Abemaciclib Treatment in Patients With Early-stage HER2-negative Breast Cancer
Official title: ONCO-ADHER: Adherence to Treatment With a Aromatase Inhibitors With or Without Abemaciclib in Patients With Early-stage, Endocrine-dependent, HER-2-negative Breast Cancer
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Early Breast Cancer
Hormone Receptor Positive Tumor
HER2-negative Breast Cancer
Keywords: breast cancer
medication adherence
CDK4/6
HR+
HER2-
aromatase inhibitor
quality of life
medication belief
Lead sponsor: Institute of Oncology Ljubljana
Sponsor class: OTHER
Collaborators: name: University of Ljubljana
First posted: 2024-10-21
Enrollment: 319
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Eligible adult women with early HR+ HER2- breast cancer patients.

Brief summary: Around 90% of breast cancer patients are diagnosed at an early stage and approximately 70%, are hormone receptor-positive and HER2-negative (HR+/HER2-). Despite advancements in adjuvant endocrine therapy, 20-30 % of early-stage BC patients relapse within the first decade post-surgery. Recent clinically meaningful therapeutic option for these patients has been cyclin-dependent kinases 4/6 inhibitors (CDK4/6 inhibitors). Abemaciclib and ribociclib, were assessed in the adjuvant setting, both showing improvement in IDFS. Abemaciclib has been approved by the FDA and EMA for HR+/HER2- early breast cancer at high risk of disease recurrence and is the first addition to Slovenian treatment regimen in routine clinical practice. Poor medication adherence can directly affect the effectiveness of treatment for early HR+/HER2- breast cancer. While adherence data in patients treated with aromatase inhibitors are available, the adherence rate in patients with early HR+/HER2- breast cancer taking abemaciclib is unclear. In this study, investigators hypothesize that patients receiving abemaciclib in combination with aromatase inhibitors will have a lower medication adherence and higher discontinuation rate compared to those receiving aromatase inhibitors alone. It is expected that patient with better quality of life, cognitive functioning and more positive attitude towards their therapy will demonstrate higher medication adherence rate. Adherence rate will also be affected by other factors, such as age and prior treatments.

Detailed description: Breast cancer (BC) is the most prevalent malignant tumour in women, with an estimated 2.308 million new cases and over 665,000 deaths globally in 2022. Around 90% of patients are diagnosed at an early stage and the majority of these cases, approximately 70%, are hormone receptor-positive and HER2-negative (HR+/HER2-). Despite advancements in adjuvant endocrine therapy that significantly lower recurrence and mortality rates, 20-30 % of early-stage BC patients experience relapse within the first decade post-surgery. Around 12% of patients with HR+/HER2- BC belong to high-risk population with 5-years invasive disease-free survival (IDFS) of 70.2% vs 90.0% in non-high-risk. The most recent clinically meaningful therapeutic option for these patients has been cyclin-dependent kinases 4/6 inhibitors (CDK4/6 inhibitors). Endocrine therapy combined with CDK4/6 inhibitors (abemaciclib, palbociclib, and ribociclib) is now the standard, most effective, and recommended treatment for these patients in the first or subsequent lines of treatment for advanced disease. Two CDK4/6 inhibitors, abemaciclib and ribociclib, have been assessed also for use in the adjuvant setting (MonarchE and NATALEE study). Both studies showed improvement in IDFS of combined endocrine therapy and CDK4/6 inhibitor vs endocrine therapy alone. Abemaciclib has been approved by both the FDA and EMA for patients with HR+/HER2- early breast cancer at high risk of disease recurrence and has therefore recently been added to Slovenian current regimen for this indication in routine clinical practice. Non-adherence to adjuvant therapy may compromise the efficacy of combined treatment in preventing disease recurrence and mortality. Some historical data report that only 60-70% of patients with early BC adhere to adjuvant therapy, making adherence a significant challenge. Key factors influencing adherence to cancer treatment include the perceived benefits of the treatment, the setting in which the treatment is administered (at home or in a hospital), the associated risks, the impact on quality of life, and the costs involved. Non-adherence often arises because patients do not experience the immediate benefits. With no visible or measurable signs of the disease and no physical symptoms of the disease, as is the case in patients receiving adjuvant treatment, and given that many would not have experienced a relapse even without adjuvant therapy, patients are much more likely to discontinue treatment if they experience adverse events/reactions (AE). Adherence to treatment with CDK4/6 inhibitors in combination with aromatase inhibitors differs from some other systemic treatments due to the continuous treatment regimen that lasts for several years without interruption. In early BC, it lasts two (abemaciclib) or three (ribociclib) years and is associated with some specific AEs. Aromatase inhibitors are associated with arthralgias, myalgias, and joint stiffness, whereas CDK4/6 inhibitors with myelotoxicity, hepatotoxicity and gastrointestinal symptoms (especially diarrhoea caused by abemaciclib). The duration of treatment, five or more vs two years (aromatase inhibitors as monotherapy vs abemaciclib in combination with aromatase inhibitors, respectively), may lead to different discontinuation rates. Despite the growing amount of real-world experiences with combined treatment with aromatase inhibitors and abemaciclib in the adjuvant setting, there is currently a lack of literature specifically exploring how patient adherence and attitudes are influenced by this combination. This gap underscores the need for further research to fully understand the impact of these therapies on medication adherence. Poor medication adherence can directly affect the effectiveness of treatment for early HR+/HER2- breast cancer. While data on medication adherence in patients taking aromatase inhibitors are available, the adherence rate in patients with early HR+/HER2- breast cancer taking abemaciclib remains unclear. Due to the differing characteristics of these treatment modalities, particularly their distinct safety profiles, medication adherence and persistence may vary between them. It is hypothesized that patients receiving abemaciclib in combination with aromatase inhibitors will have a lower medication adherence and higher discontinuation rate compared to those receiving aromatase inhibitors alone. It's also expected that patient with better quality of life, better cognitive functioning and more positive attitude towards their therapy will demonstrate higher medication adherence rate. Additionally, it's anticipated that other factors, such as age and prior treatments, will also contribute to adherence rates.

Eligibility criteria: Inclusion Criteria:

* Female,
* Early HR+/HER-2- BC,
* Patient is receiving adjuvant therapy with an aromatase inhibitor (letrozole, anastrozole or exemestane), with or without a CDK4/6 inhibitor abemaciclib, for no more than 18 months,
* Treatment of BC is being conducted at OIL,
* Patient has mandatory health insurance through Health Insurance Institute of Slovenia,
* Patient understands Slovenian language, and
* Patient agrees to participate in the study and provides written informed consent.

Exclusion Criteria:

* Metastatic HR+/HER-2- BC
* Previous treatment for BC with an aromatase inhibitor, with or without a CDK4/6 inhibitor, due to BC.

Primary outcomes:
measure: Medication adherence in proportion of days covered (PDC)
timeFrame: Month 3 after starting dose
measure: Medication adherence in proportion of days covered (PDC)
timeFrame: Month 6 after starting dose
Secondary outcomes:
measure: Quality of life, assessed with QLQ-C30, affecting medication adherence
timeFrame: Baseline visit
measure: Quality of life, assessed with QLQ-C30, affecting medication adherence
timeFrame: Month 3
measure: Quality of life, assessed with QLQ-C30, affecting medication adherence
timeFrame: Month 6
measure: Quality of life, assessed with QLQ-BR23, affecting medication adherence
timeFrame: Baseline visit
measure: Quality of life, assessed with QLQ-BR23, affecting medication adherence
timeFrame: Month 3
measure: Quality of life, assessed with QLQ-BR23, affecting medication adherence
timeFrame: Month 6
measure: Belief about medications affecting medication adherence
timeFrame: Baseline visit
measure: Belief about medications affecting medication adherence
timeFrame: Month 3
measure: Belief about medications affecting medication adherence
timeFrame: Month 6
measure: Cognitive functioning affecting medication adherence
timeFrame: Baseline visit
measure: Cognitive functioning affecting medication adherence
timeFrame: Month 3
measure: Cognitive functioning affecting medication adherence
timeFrame: Month 6
measure: Previous treatment affecting medication adherence
timeFrame: Baseline visit
measure: Adverse events affecting medication adherence
timeFrame: Baseline visit
measure: Adverse events affecting medication adherence
timeFrame: Month 3
measure: Adverse events affecting medication adherence
timeFrame: Month 6
Other outcomes:
Locations:
Study officials:
affiliation: Institute of Oncology Ljubljana, Slovenia
name: Erika Matos, PhD
role: PRINCIPAL_INVESTIGATOR
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