DOSABEMA-Pharmacokinetic model of abemaciclib: correlation with severe diarrhea as the primary toxicity endpoint in patients with hormone receptor-positive localized breast cancer

Condition studied

HR+, HER2- breast cancer at high risk of recurrence

Investigational medicinal product(s)

Eligibility

Primary endpoint

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.

Endpoint detail

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., Validation of the mixed-effects PK/PD model using standard diagnostic tools (diagnostic plots of data fit, visual predictive checks, estimation precision, shrinkage)., 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.