Individualized regimens and dosing of targeted therapies in oncology

Abstract

Over the past decades, targeted therapies have transformed the landscape of cancer treatment. This thesis focuses on further improving treatment and treatment regimens of targeted therapy within medical oncology. The first part focuses on enhancing therapeutic drug monitoring. A method was developed for the home-based measurement of cabozantinib levels, which can be immediately implemented in clinical practice. Additionally, the importance of assessing intra-patient variability in patients taking pazopanib is described; patients exhibiting high variability in pazopanib exposure experienced poorer clinical outcomes. Regarding afatinib, the development of a model in order to predict the optimal dose for each patient is described. The second part focuses on adjusting treatment regimens to optimize the complex balance between efficacy, toxicity, cost-effectiveness, and patient-reported outcomes. For patients treated with cabozantinib, it was found that taking cabozantinib with breakfast rather than on an empty stomach resulted in equivalent drug exposure—a finding that can be directly applied in clinical practice. Finally, an alternative treatment regimen was developed for enfortumab vedotin (a drug for bladder cancer) that achieves equivalent exposure at a lower cost. Through effective collaboration among medical oncologists, pharmacists, and other stakeholders, the findings of this thesis can lead to further improvements in care.