Model-Informed Development of a Cost-Saving Dosing Regimen for Sacituzumab Govitecan

Abstract

Background: The antibody-drug conjugate sacituzumab govitecan is approved for metastatic triple-negative breast cancer and has shown promising results in various other types of cancer. Its costs may limit patient access to this novel effective treatment modality.

Objective: The purpose of this study was to develop an evidence-based rational dosing regimen that results in targeted drug exposure within the therapeutic range while minimizing financial toxicity, to improve treatment access.

Patients and methods: Exposure equivalent dosing strategies were developed based on pharmacokinetic modeling and simulation by using the published pharmacokinetic model developed by the license holder. The alternative dose was based on the principle of using complete vials to prevent spillage and on the established non-linear relationship between body weight and systemic exposure. Equivalent exposure compared to the approved dosing regimen of 10 mg/kg was aimed for. Equivalent exposure was conservatively defined as calculated geometric mean ratios within the 0.9-1.11 boundaries for area under the concentration-time curve (AUC), trough concentration (C_trough) and maximum concentration (C_max) of the alternative dosing regimen compared to the approved dosing regimen. Since different vial sizes are available for the European Union (EU) and United States (US) market, because body weight distributions differ between these populations, we performed our analysis for both scenarios.

Results: Dosing regimens of sacituzumab govitecan for the EU (< 50 kg: 400 mg, 50-80 kg: 600 mg, and > 80 kg: 800 mg) and US population (< 40 kg: 360 mg, 40-65 kg: 540 mg, 65-90 kg: 720 mg, and > 90 kg: 900 mg) were developed, based on weight bands. The geometric mean ratios for all pharmacokinetic outcomes were within the predefined equivalence boundaries, while the quantity of drug used was 21.5% and 19.0% lower for the EU and US scenarios, respectively.

Conclusions: With the alternative dosing proposal, an approximately 20% reduction in drug expenses for sacituzumab govitecan can be realized while maintaining an equivalent and more evenly distributed exposure throughout the body weight range, without notable increases in pharmacokinetic variability.

Fig. 1

A Distribution body weight of studied population (EU). B Comparison of exposure metrics (C_trough 1st cycle) between registered dose and alternative dose. C C_trough at steady state distribution per body weight group registered dose. D C_trough at steady state distribution per body weight group alternative dose. E Comparison of exposure metrics (C_trough steady state) between registered dose and alternative dose. F Comparison of exposure metrics (AUC first cycle) between registered dose and alternative dose. AUC area under the concentration–time curve, C_min minimum blood plasma concentration, C_trough trough concentration, EU European Union

Fig. 2

A Distribution body weight of studied population (USA). B Comparison of exposure metrics (C_trough 1st cycle) between registered dose and alternative dose. C C_trough at steady state distribution per body weight group registered dose. D C_trough at steady state distribution per body weight group alternative dose. E Comparison of exposure metrics (C_trough steady state) between registered dose and alternative dose. F Comparison of exposure metrics (AUC 1st cycle) between registered dose and alternative dose. AUC area under the concentration–time curve, C_trough trough concentration, USA United States of America