TDM-Based Tailored Dosing of Durvalumab in Lung Cancer Patients: A Comprehensive Population Pharmacokinetic-Pharmacoeconomic Evaluation

BACKGROUND: The increasing use of immune checkpoint inhibitors, such as durvalumab, places a significant financial burden on healthcare systems, strains hospital capacities, and contributes to environmental concerns.

OBJECTIVE: We aimed to develop alternative dosing strategies to optimize durvalumab administration, reduce unnecessary drug use, and ensure sustainable cancer care without sacrificing efficacy.

METHODS: Using the population pharmacokinetic model developed by the licensing holder, we designed two alternative dosing strategies for non-small cell lung cancer based on therapeutic drug monitoring. Adjustments were made to the dose or administration interval, following regulatory standards for in silico dose optimization. A pharmacoeconomic evaluation was conducted to estimate potential cost savings from a medical perspective.

RESULTS: Both alternative strategies achieved high exposure levels, with 98.1-99.0% of patients exceeding a predefined efficacy target, surpassing the 95.4% predicted by the license holder for the approved 10 mg/kg 2-weekly regimen. They also reduced overall drug exposure by 7-24% and eliminated drug wastage, resulting in an average annual cost reduction of €25,163 (22.9%) per patient.

CONCLUSION: Therapeutic drug monitoring-guided adjustments for durvalumab offer a potentially cost-saving way to optimize drug use, reduce healthcare burdens, and lessen environmental impact while ensuring adequate patient exposure. Our proposal's evidence provides a solid basis for a non-inferiority study.