瘤剂量选择在随后的指示:我们可以从FDA批准的瘤药物中学到什么?
Huy X Ngo1, Elise Oh1, Chunze Li1
1Department of Clinical Pharmacology, Genentech, Inc., South San Francisco, California, USA.
Clinical therapeutics
|September 20, 2024
概括
大多数瘤学药物保持初始剂量方案,以适应新的适应症. 新型瘤药物的剂量变化主要是由安全性和耐受性问题驱动的,影响治疗策略.
科学领域:
- 瘤学 药物开发 药物开发
- 药理学 药理学是指药理学的学科.
- 临床试验设计 临床试验设计
背景情况:
- 癌症药物开发的景观已经超越了传统的细胞毒性化疗.
- 瘤学药物通常会获得随后的批准,用于额外的指示,如单疗法或组合治疗.
- 缺乏对这些后续适应症的剂量选择策略的系统审查.
研究的目的:
- 审查FDA批准的瘤药物的后续指示的剂量选择策略.
- 分析如何为新型瘤药物新指标建立剂量方案.
主要方法:
- 利用Drugs@FDA数据库识别2010年至2023年间批准的新分子实体 (NME).
- 包括在分析中获得超过一个批准的适用症的NME.
- 评估了67种新瘤药物的剂量方案,这些新瘤药物已被批准用于多种适应症.
主要成果:
- 72%的NME在随后的指示中保留了相同或临床相当的剂量方案.
- 在28%的NME中,剂量方案被改变,安全性和耐受性是变化的主要驱动因素.
- 影响剂量变化的其他因素包括瘤生物学,疾病负担,药理动力学和益处风险概况.
结论:
- 最初选择安全,耐受和有效的剂量方案至关重要,因为次于最佳的选择可能需要在以后的指示中进行更改.
- 利用临床前和临床数据可以阐明适应症之间的药理动力学和药理动力学差异,有助于随后的剂量选择.
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