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

• Published in: Cancers 2023-01, Vol.15 (1), p.316
• Main Authors: Bandiera, Carole, Locatelli, Isabella, Courlet, Perrine, Cardoso, Evelina, Zaman, Khalil, Stravodimou, Athina, Dolcan, Ana, Sarivalasis, Apostolos, Zurcher, Jean-Philippe, Aedo-Lopez, Veronica, Dotta-Celio, Jennifer, Peters, Solange, Guidi, Monia, Wagner, Anna Dorothea, Csajka, Chantal, Schneider, Marie P
• Format: Article
• Language: English
• Subjects: Breast cancer; Cancer; Cancer therapies; Coronaviruses; Cyclin-dependent kinase 4; Cyclin-dependent kinases; Drug dosages; Drug therapy; Feedback; Leukocytes (neutrophilic); Metastases; Neutropenia; Oncology, Experimental; Oral administration; Patient compliance; Patients; Pharmacists; Pharmacodynamics; Pharmacokinetics; Sociodemographics; Toxicity
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15010316

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% (Δ1.95%, 95% CI 1.1−2.9%), respectively. The impact of the intervention was larger in patients diagnosed with MBC for >2 years (Δ3.6%, 95% CI 2.1−5.4%), patients who received >4 cycles before inclusion (Δ3.1%, 95% CI 1.7−4.8%) and patients >65 (Δ2.3%, 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.