An evaluation of cetuximab dosing strategies using pharmacokinetics and cost analysis.

OBJECTIVES: Cetuximab dosing is based on body surface area (BSA), an approach that is associated with significant wastage due to available vial sizes. NHS England recently introduced an alternative strategy for cetuximab dosing based on dose banding. The aim of this work was to investigate approaches to cetuximab dosing to improve its cost-effectiveness. METHODS: A simulation study using a population pharmacokinetic model was used to assess the performance of dosing strategies using exposure, probability of target attainment and cost. Two dosage regimens (500 and 400/250 mg/m2 ) were investigated; 5% and 10% dose banding, fixed and optimised dosing strategies were evaluated and compared to BSA strategy. KEY FINDINGS: The percentage of the total cost associated with wastage for the 400/250 mg/m2 regimen were 8.75%, 5.13%, 3.61%, 9.2% and 0% for BSA; 5 and 10% bands; fixed and optimal strategies, respectively. Similar results were obtained for 500 mg/m2 regimen. In comparison with BSA strategy, other strategies have comparable or improved performance. Optimised strategy showed consistent performance and ensures equal exposure and probability of target attainment. CONCLUSIONS: Cost-effectiveness of cetuximab treatment can be improved with alternative strategies by reducing wastage without compromising exposure.

Dose Rationalization of Pembrolizumab and Nivolumab Using Pharmacokinetic Modeling and Simulation and Cost Analysis.

Pembrolizumab and nivolumab are highly selective anti-programmed cell death 1 (PD-1) antibodies approved for the treatment of advanced malignancies. Variable exposure and significant wastage have been associated with body size dosing of monoclonal antibodies (mAbs). The following dosing strategies were evaluated using simulations: body weight, dose banding, fixed dose, and pharmacokinetic (PK)-based methods. The relative cost to body weight dosing for band, fixed 150 mg and 200 mg, and PK-derived strategies were -15%, -25%, + 7%, and -16% for pembrolizumab and -8%, -6%, and -10% for band, fixed, and PK-derived strategies for nivolumab, respectively. Relative to mg/kg doses, the median exposures were -1.0%, -4.6%, + 27.1%, and +3.0% for band, fixed 150 mg, fixed 200 mg, and PK-derived strategies, respectively, for pembrolizumab and -3.1%, + 1.9%, and +1.4% for band, fixed 240 mg, and PK-derived strategies, respectively, for nivolumab. Significant wastage can be reduced by alternative dosing strategies without compromising exposure and efficacy.