ABEMACICLIB for Hormone receptor-positive, HER2-negative breast cancer at high risk of recurrence

Inclusion criteria

• {"criterion_text":"- Women aged ≥ 18 with breast cancer of any histology\n- Must be affiliated to the social security system or benefit from it through a third party\n- Have signed the consent form for the study after reading the information note\n- Type Luminous A or B with positive hormone receptors (>10% expression for oestrogen receptor and/or progesterone receptor) and negative or low HER2 epidermal growth factor receptor (as defined by GEFPICS1)\n- Stage 2 or stage 3 according to the international classification, translated into the SENORIF recommendation\n- Who have undergone complete excision surgery (R0 on the invasive tumour and/or on the ductal entity in situ) after neoadjuvant or non-neoadjuvant chemotherapy;\n- Defined as being at high risk of recurrence according to the Monarch-E study, at the initial diagnosis of the disease: either ≥ 4 axillary nodes involved (involvement ≥N2), or 1-3 axillary nodes involved (involvement ≥N1) associated with an Elston Ellis grade 3 or a tumour ≥ 5 cm\n- Initiation of adjuvant abemaciclib therapy combined with hormone therapy\n- Patient ECOG performans status between 0 ≤2\n- Patient with a PNN count defined as normal prior to the first dose of abemaciclib, i.e. an absolute PNN count ≥ 1500/mm3 (≥ 1.5 x 109/L) without GCSF injection within 15 days prior to the biological work-up, as well as a platelet count ≥ 100 000/mm3 and a haemoglobin level ≥ 8g/dL.\n- Patient with the psychological and mental capacity to understand the protocol and sign the consent form alone"}

Exclusion criteria

• {"criterion_text":"- Previous treatment with an anti-CDK4/6 (palbociclib, ribociclib, abemaciclib) for any indication.\n- History of invasive cancer of any histology in the last 2 years, with the exception of superficial skin tumours, not considered to be in complete remission.\n- Presence of functional or inflammatory colorectal disease (Crohn's disease, ulcerative colitis) causing chronic diarrhoea (as defined by the WHO as at least 3 bowel movements per day and/or liquid stools for at least 1 month).\n- Patients who have undergone total gastrectomy or suffer from short bowel syndrome\n- Patients unable to sign the consent form for social reasons (illiteracy) or physical reasons (central nervous system disease).\n- Persons benefiting from enhanced protection, namely minors, persons deprived of their liberty by judicial or administrative decision, persons staying in a health or social care institution, adults under legal protection and, finally, patients in emergency situations.\n- Pregnant or breastfeeding women, women of childbearing age who are not using highly effective contraception (e.g., double-barrier contraception) during treatment and for at least 3 weeks after stopping treatment (The duration of contraception required for concomitant treatments, if any, should also be taken into account.)\n- Hypersensitivity to any of the excipients listed in section 6.1 of the abemaciclib (Verzenios) summary of product characteristics."}

Primary endpoints

• {"endpoint_text":"- The probability of severe diarrhoea (grades 2, 3 and 4 according to CTCAE v5.0) occurring as a result of exposure to abemaciclib and its metabolites will be characterised by a mixed-effects joint model, combining longitudinal, pharmacokinetic (continuous) and toxicity (survival) data.","definition_or_measurement_approach":"Severe diarrhoea defined as CTCAE v5.0 grades 2-4; characterised by a mixed-effects joint PK/PD model combining longitudinal pharmacokinetic concentration data for abemaciclib and metabolites and toxicity (survival-type) data to model probability of event."}

Secondary endpoints

• {"endpoint_text":"- The probability of severe neutropenia (grades 3 and 4 according to the current CTCAE) occurring as a result of exposure to abemaciclib and its metabolites will be characterised by a mixed-effects joint model, combining longitudinal pharmacokinetic data pharmacokinetic (continuous type) and pharmacodynamic (neutrophil concentration, continuous type) data.","definition_or_measurement_approach":"Severe neutropenia defined as CTCAE grades 3-4; characterised using a mixed-effects joint PK/PD model combining longitudinal PK concentrations and continuous neutrophil counts."}
• {"endpoint_text":"- Validation of the mixed-effects PK/PD model using standard diagnostic tools (diagnostic plots of data fit, visual predictive checks, estimation precision, shrinkage).","definition_or_measurement_approach":"Model validation using diagnostic plots, Visual Predictive Checks, assessment of estimation precision and shrinkage."}
• {"endpoint_text":"- The ‘fu’ of abemaciclib concentrations will be modelled within the mixed-effects PK/PD model, and any correlation with clinical and biological covariates will be evaluated.","definition_or_measurement_approach":"Free fraction ('fu') of abemaciclib concentrations will be modelled in the PK/PD model and correlations with clinical/biological covariates assessed."}

France

Earliest CTIS Part Ii Submission Date

10-11-2025

Latest Decision Or Authorization Date

06-01-2026

Processing Time Days

57

Number Of Sites

4

Number Of Participants

235

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Poitiers

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France