Evaluation of Adherence to Cell Cycle Inhibitors Used as Adjuvant Therapy in Patients With Localized Breast Cancer at High Risk of Recurrence.

NCT07443774 | Not Yet Recruiting DMC

• 2 other identifiers: 38RC25.04032025-A02911-48
• Study Type: observational
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

Hormone receptor-positive (HR+) breast cancers represent the most common histological subtype of breast cancer, accounting for approximately 75% of cases, regardless of HER2 (human epidermal growth factor receptor 2) status (1). Adjuvant endocrine therapy (ET), including tamoxifen and aromatase inhibitors (AIs), is an effective pharmacological treatment for improving the prognosis of HR+ breast cancer, reducing the risk of recurrence by up to 50% (2-3-4-6). Despite its proven prognostic benefit, the full potential of endocrine therapy is not realized due to patient non-adherence (i.e., failure to comply with prescribed treatment). Adjuvant endocrine therapy is generally prescribed for a duration of 5 to 10 years. However, up to 40% of patients discontinue treatment prematurely, and 30% take the medication less frequently than prescribed. Poor adherence and low treatment persistence carry a substantial mortality burden: non-adherence is associated with a 49% increase in all-cause mortality. A retrospective analysis of a large database including more than 8,700 patients showed a 10-year survival rate of 80.7% among women who continued treatment, compared with 73.6% among those who discontinued adjuvant therapy prematurely (p \< 0.001). Among patients who continued treatment, the survival rate was 82% in those who were fully adherent, versus 78% in those who were only partially adherent (7-16). The literature has documented a wide range of risk factors associated with non-adherence to or discontinuation of long-term adjuvant endocrine therapy. Treatment-related adverse effects, including hot flashes, joint stiffness, and sexual dysfunction, are common and may lead to treatment discontinuation. Fear of side effects may also prevent some patients from initiating or maintaining endocrine therapy. Others may not be fully convinced of the necessity of adjuvant endocrine therapy, particularly in the absence of overt signs of cancer. In addition, supportive care required to manage side effects is often inadequately reimbursed, making low income-combined with broader socioeconomic factors-a potential barrier to optimal adherence. Some patients may also experience difficulties remembering to take their medication regularly. The relative importance and contribution of these factors to non-adherence may evolve over time. Other factors may also play a role, including sociodemographic characteristics (low income, living alone, or unemployment). Nevertheless, a residual risk of recurrence persists after five years of well-conducted standard endocrine therapy, extending up to two decades after diagnosis, particularly in patients with early-stage breast cancer stages II and III. In this higher-risk population, two phase III trials, monarchE and NATALEE, have recently evaluated the addition of a cell cycle inhibitor (CDK4/6 inhibitor) to standard adjuvant endocrine therapy and reported positive results with a reduction in the risk of relapse. In the NATALEE trial, quality of life was assessed in all patients in the ribociclib plus aromatase inhibitor group (n = 2,549) versus the aromatase inhibitor alone group (n = 2,552). Mean scores did not differ significantly from baseline for any of the analyzed domains. Similarly, no significant change from baseline was observed in either treatment group. However, it is important to note that 33.8% of patients discontinued ribociclib and 20% discontinued both endocrine therapy and ribociclib in the NATALEE trial, which is consistent with data from the literature. In the monarchE trial, 16.6% of patients discontinued abemaciclib, and 6% discontinued both abemaciclib and endocrine therapy, while only 0.8% discontinued endocrine therapy in the control group. These findings are not consistent with previously published data. To our knowledge, no real-world study has evaluated CDK4/6 inhibitors in combination with endocrine therapy in the adjuvant treatment of HR+/HER2-negative breast cancer. AdheRA is a prospective multicenter cohort study of patients with early-stage HR+/HER2-negative breast cancer at high risk of recurrence, eligible for a combination of endocrine therapy and a CDK4/6 inhibitor such as abemaciclib or ribociclib in the adjuvant setting, aiming to assess treatment adherence and the reasons for non-adherence.

Conditions

ER+ Breast Cancer; Breast Cancer; Early Breast Cancer; Endocrine Therapy; Abemaciclib; Ribociclib

Keywords

early breast cancer; celle cycle inhibitors; endocrine therapy; adjuvant setting

Outcome Measures

Primary Outcomes (1)

• The primary objective of this study is to evaluate adherence to iCDK4/6 treatment in patients with localized hormone receptor-positive breast cancer at high risk of recurrence, within a real-world setting.

  The percentage of early discontinuation of iCDK4/6 therapy will be assessed. Early discontinuation is defined as cessation of treatment prior to 20 months (of a planned 24-month duration) for abemaciclib or prior to 30 months (of a planned 36-month duration) for ribociclib.

  Early discontinuation is defined as cessation of treatment prior to 20 months (of a planned 24-month duration) for abemaciclib or prior to 30 months (of a planned 36-month duration) for ribociclib.

Secondary Outcomes (5)

• The objective is to estimate the proportion of patients who did not initiate iCDK4/6 therapy.

  From day 1 to 2 years for Abemaciclib or 3 years for Ribociclib

• To estimate the mean treatment completion rate for iCDK4/6 therapy and endocrine therapy.

  From day 1 to 2 years for Abemaciclib or 3 years for Ribociclib

• To estimate the proportion of dose modifications and to describe the reasons for these modifications.

  From day 1 to 2 years for Abemaciclib or 3 years for Ribociclib.

• To describe risk factors associated with non-adherence.

  From day 1 to 2 years for Abemaciclib or 3 years for Ribociclib

• To evaluate invasive disease-free survival.

  From day 1 to 2 years for Abemaciclib or 3 years for Ribociclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be selected from those with localized, high-risk, hormone receptor-positive, HER2-negative breast cancer who are treated at one of the two participating centers and receive adjuvant therapy between 2023 and 2028, and who are eligible for treatment with CDK4/6 inhibitors. Patients will be seen in dedicated consultations, according to international recommendations, at least every six months, to assess treatment adherence, tolerability, and risk of recurrence. Recruitment will therefore take place directly during these consultations. All patients for whom an indication for iCDK4/6 therapy is established will be eligible to participate in the study. This indication is determined during multidisciplinary tumor board meetings, which are standard practice in the patient care pathway. The end of the inclusion period has been arbitrarily set five years later, in order to obtain a sufficient number of patients.

You may qualify if:

• Male or female patients aged ≥18 years.
• Operable invasive breast carcinoma of no special type, hormone receptor-positive / HER2-negative (estrogen receptor expression \>10% with or without progesterone receptor expression \>10%; HER2-negative defined as score 0, 1+, or 2+ non-amplified).
• M0 disease according to the TNM 2018 classification.
• Having undergone curative surgery of the primary breast tumor.
• Having received adjuvant radiotherapy, if indicated.
• Indication for combined adjuvant endocrine therapy and iCDK4/6 therapy validated during a multidisciplinary tumor board meeting.
• Initiation of adjuvant endocrine therapy combined with a CDK4/6 inhibitor between June 2023 and June 2028.
• No objection to participation in the study.
• Affiliation with the national health insurance system.
• Medical, geographical, sociological, psychological, or legal conditions that could prevent the patient from completing the study or from providing informed non-opposition.
• Locally advanced, non-operable disease or metastatic disease not amenable to curative-intent treatment

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (1)

CHU Grenoble Alpes

Grenoble, 38043, France

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Emmanuelle JACQUET

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emmanuelle JACQUET, MD, PhD

CONTACT

33 0)476765451; ejacquet1@chu-grenoble.fr

Adrien MONARD, PhD

CONTACT

33 (0)4 76 70 70 22; adrien.monard@ghm-grenoble.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2026
• First Posted: March 2, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): December 1, 2031
• Last Updated: March 2, 2026

Record last verified: 2026-02

Locations

FR (1)