Adherence to the CDK 4/6 Inhibitor Palbociclib and Omission of Dose Management Supported by Pharmacometric Modelling as Part of the OpTAT Study

Simple Summary Medication adherence to CDK4/6 inhibitors such as palbociclib, prescribed as a cyclic oral anticancer therapy in women diagnosed with advanced breast cancer, may be suboptimal. We evaluated adherence to palbociclib and its impact on pharmacokinetic and pharmacodynamic (PK-PD) profiles. Patients included in the OpTAT study used an electronic monitor to register each drug intake event and were randomized into the intervention (i.e., interprofessional medication adherence program) or control group (i.e., usual care). Patients in the intervention group (n = 19) had a higher and more stable adherence than control patients (n = 19). The intervention had a larger effect on patients older than 65 and in patients with longer treatment and disease experience. The PK-PD analysis showed that catching up on a missed dose at the end of the cycle increases the risk of severe neutropenia in the next cycle. The interprofessional healthcare team should closely monitor patients' cycle management to improve prescriptions and decrease toxicity. The cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) palbociclib is administered orally and cyclically, causing medication adherence challenges. We evaluated components of adherence to palbociclib, its relationship with pharmacokinetics (PK), and drug-induced neutropenia. Patients with metastatic breast cancer (MBC) receiving palbociclib, delivered in electronic monitors (EM), were randomized 1:1 to an intervention and a control group. The intervention was a 12-month interprofessional medication adherence program (IMAP) along with monthly motivational interviews by a pharmacist. Implementation adherence was compared between groups using generalized estimating equation models, in which covariates were included. Model-based palbociclib PK and neutrophil profiles were simulated under real-life implementation scenarios: (1) optimal, (2) 2 doses omitted and caught up at cycle end. At 6 months, implementation was slightly higher and more stable in the intervention (n = 19) than in the control (n = 19) group, 99.2% and 97.3% (Delta 1.95%, 95% CI 1.1-2.9%), respectively. The impact of the intervention was larger in patients diagnosed with MBC for >2 years (Delta 3.6%, 95% CI 2.1-5.4%), patients who received >4 cycles before inclusion (Delta 3.1%, 95% CI 1.7-4.8%) and patients >65 (Delta 2.3%, 95% CI 0.8-3.6%). Simulations showed that 25% of patients had neutropenia grade >= 3 during the next cycle in scenario 1 versus 30% in scenario 2. Education and monitoring of patient CDK4/6i cycle management and adherence along with therapeutic drug monitoring can help clinicians improve prescription and decrease toxicity.