Dose-finding designs for trials of molecularly targeted agents and immunotherapies.
Dose-finding designs for trials of molecularly targeted agents and immunotherapies.
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DOI：
10.1080/10543406.2017.1289952
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发表时间：
2017
影响因子：
1.1
通讯作者：
Lee SM
中科院分区：
文献类型：
--
作者：
Chiuzan C;Shtaynberger J;Manji GA;Duong JK;Schwartz GK;Ivanova A;Lee SM
最近，分子靶向药物（MTA）和免疫疗法的早期试验激增。与细胞毒性疗法相比，这些新疗法具有不同的毒性特征。MTA可以从新的试验设计中受益，这些设计允许纳入低级别毒性、迟发性毒性、增加疗效终点以及在指定目标毒性概率方面的灵活性。为了研究这些方法的采用程度，我们对2008年至2014年间发表的描述1期肿瘤学试验的文章进行了Web of Science搜索。试验根据使用的剂量探索设计和研究的药物类型进行分类。在符合我们标准的1，712项剂量探索试验中，1，591项（92.9%）采用了基于规则的设计，92项（5.4%;范围2.3%（2009年）至9.7%（2014年））采用了基于模型的设计或新型设计。超过一半的试验测试了MTA或免疫疗法。在MTA和免疫治疗试验中，5.8%使用基于模型的方法，而化疗或放疗试验分别为3.9%和8.3%。虽然自2007年以来，使用新型剂量探索设计的试验比例增加了两倍，但只有7.1%的试验使用了新型设计。
Recently, there has been a surge of early phase trials of molecularly targeted agents (MTAs) and immunotherapies. These new therapies have different toxicity profiles compared to cytotoxic therapies. MTAs can benefit from new trial designs that allow inclusion of low-grade toxicities, late-onset toxicities, addition of an efficacy endpoint, and flexibility in the specification of a target toxicity probability. To study the degree of adoption of these methods, we conducted a Web of Science search of articles published between 2008 and 2014 that describe phase 1 oncology trials. Trials were categorized based on the dose-finding design used and the type of drug studied. Out of 1,712 dose-finding trials that met our criteria, 1,591 (92.9%) utilized a rule-based design, and 92 (5.4%; range 2.3% in 2009 to 9.7% in 2014) utilized a model-based or novel design. Over half of the trials tested an MTA or immunotherapy. Among the MTA and immunotherapy trials, 5.8% used model-based methods, compared to 3.9% and 8.3% of the chemotherapy or radiotherapy trials, respectively. While the percentage of trials using novel dose-finding designs has tripled since 2007, only 7.1% of trials use novel designs.