Pharmacokinetic Boosting of Osimertinib

Osimertinib is a new targeted agent registered for the treatment of patients with EGFR-mutated NSCLC. However, the costs of those new treatments are extremely high. Osimertinib is mainly metabolized by CYP3A4, and partially by CYP3A5. Combination of osimertinib with a strong CYP3A4-inhibitor may result in a smaller first-pass effect and a decreased clearance of osimertinib, thereby increasing the exposure to osimertinib. Cobicistat is a strong CYP3A4-inhibitor, this mechanism may be used to boost osimertinib, as is done for other drugs, mainly drugs used to treat HIV-infected patients. Using this personalized treatment approach and combining the concepts of therapeutic drug monitoring (TDM) and pharmacokinetic boosting, osimertinib therapy could become much more cost-effective. By reducing the necessary dose of osimertinib, this strategy may ultimately result in a significant reduction in drug costs, as the additional expenditure for the CYP3A4 inhibitor and blood sample analysis are negligible compared to the price of osimertinib.