根据模型开发节省成本的萨妥珠单抗戈维替康给药方案。

IF 4.4 3区 医学 Q2 ONCOLOGY
Targeted Oncology Pub Date : 2024-09-01 Epub Date: 2024-06-18 DOI:10.1007/s11523-024-01075-8
Dirk J A R Moes, Jeroen J M A Hendrikx, Henk-Jan Guchelaar, Ron H J Mathijssen, J L Bakker, Vincent O Dezentjé, Nikki de Rouw, Nielka P van Erp, Egbert F Smit, Michel M van den Heuvel, Thijs H Oude Munnink, Maartje van Kats, Sander Croes, Judith R Kroep, Juliette Zwaveling, Rob Ter Heine
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引用次数: 0

摘要

背景:抗体药物共轭物sacituzumab govitecan已被批准用于治疗转移性三阴性乳腺癌,并在其他各种癌症中显示出良好的疗效。其成本可能会限制患者使用这种新型有效的治疗方式:本研究的目的是开发一种以证据为基础的合理给药方案,使靶向药物暴露在治疗范围内,同时最大限度地减少经济毒性,以提高治疗的可及性:根据药代动力学建模和模拟,利用许可证持有人开发的已公布的药代动力学模型,制定了暴露等效剂量策略。替代剂量基于使用完整药瓶以防止溢出的原则,以及体重与全身暴露量之间已确立的非线性关系。与已批准的 10 毫克/千克剂量方案相比,目标是达到等效暴露量。保守的定义是,与已批准的给药方案相比,替代给药方案的浓度-时间曲线下面积(AUC)、谷浓度(Ctrough)和最大浓度(Cmax)的几何平均比值在 0.9-1.11 范围内。由于欧盟(EU)和美国(US)市场上有不同规格的药瓶,而且这些人群的体重分布也不相同,因此我们对两种情况都进行了分析:结果:根据体重带,我们为欧盟(80 千克:800 毫克)和美国(90 千克:900 毫克)人群制定了sacituzumab govitecan 的给药方案。所有药代动力学结果的几何平均比均在预定的等效范围内,而欧盟和美国方案的用药量分别降低了21.5%和19.0%:结论:采用替代给药方案,可以将萨西妥珠单抗-戈维替康的用药费用降低约20%,同时在整个体重范围内保持等效且分布更均匀的暴露量,而不会显著增加药代动力学变异性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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 (Ctrough) and maximum concentration (Cmax) 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.

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来源期刊
Targeted Oncology
Targeted Oncology 医学-肿瘤学
CiteScore
8.40
自引率
3.70%
发文量
64
审稿时长
>12 weeks
期刊介绍: Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes: Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches. Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways. Current Opinion articles that place interesting areas in perspective. Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations. Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement. Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.
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