MODEL-informed nivolumab less frequent dosing using virtual patients with solid tumors

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Less frequent nivolumab dosing has been assessed for more efficient dosing, but there is no conclusive evidence. In this research, we suggested an appropriate model-informed drug dosing using virtual patients collected from the results of multiple clinical studies to provide a rationale for less frequent dosing. A pharmacokinetic model was developed using a virtual solid tumor cohort generated through simulation from final models of previous nivolumab pharmacokinetic studies. Simulations were performed for regimens ranging from standard doses to extended intervals of up to 8 weeks, specifically 12 mg/kg and 960 mg. The primary analysis focused on the attainment of a minimum effective concentration at steady state. Here we show that nivolumab clearance increases as body weight increases, and that a higher clearance is observed in female patients and/or patients with greater physical restriction (baseline performance status ≥ 1). Volume of distribution also increases with body weight and is higher in female patients. The predicted steady-state trough concentrations remain well above the minimum effective concentration of 2.5 μg/mL across all evaluated scenarios, including the maximally extended 8-week intervals. The pooled population pharmacokinetic analysis using virtual patients provides evidence supporting the pharmacokinetic feasibility of extending the nivolumab dosing interval up to 8 weeks. These findings suggest that less frequent dosing regimens maintain therapeutic drug exposure while potentially reducing the treatment burden on patients and healthcare systems. Nivolumab is a common cancer treatment usually given every two or four weeks. This study aimed to see if patients could safely receive the drug less often to make treatment more convenient. We used computer programs to create a group of 288 virtual patients and simulated how the drug stays in their bodies when given at longer intervals. We found that even when the time between doses was stretched to eight weeks, the amount of medicine in the blood remained high enough to be effective. This means that many patients may only need treatment once every two months instead of every two weeks. This change could greatly reduce hospital visits and improve the daily lives of patients without losing the benefits of the medicine. Lee et al. conduct a model-informed pharmacokinetic simulation using a virtual solid tumor cohort to evaluate the feasibility of extending nivolumab dosing intervals. They demonstrate that predicted trough concentrations remain above the minimum effective threshold across all scenarios, supporting the extension of dosing intervals up to eight weeks.

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