The clinical viewpoint: definitions, limitations of RECIST, practical considerations of measurement.
The clinical viewpoint: definitions, limitations of RECIST, practical considerations of measurement.
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DOI：
10.1158/1078-0432.ccr-12-2935
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发表时间：
2013-05-15
期刊：
影响因子：
--
通讯作者：
Socinski MA
中科院分区：
文献类型：
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作者：
Villaruz LC;Socinski MA
在临床试验设计中选择终点时，重要的是要考虑该终点是可靠测量的且具有临床意义。因此，总生存期（OS）传统上被认为是临床试验设计中最具临床相关性和说服力的终点，只要它伴随着生活质量的保护。然而，由于可行性问题（样本量较小和随访时间较短），无进展生存期（PFS）在临床试验设计中越来越突出。PFS的优点是不仅考虑了缓解性疾病，还考虑了稳定性疾病，这是复发性和难治性背景下特别重要的问题，其中治疗通常与最小至零缓解相关，但仍可能带来生存优势。最后，PFS在分子选择的人群中具有显著优势，在这些人群中，由于交叉效应，OS优势难以检测。通过了解PFS作为主要终点引入的局限性和偏倚，我们认为PFS不仅是一种可行的，而且是OS在分子定义的癌症人群中评估选定新型靶向治疗疗效的必要替代方案。最终，临床试验终点的选择不应基于一刀切的方法;相反，它应基于正在测试的治疗策略和研究人群的具体情况。
In selecting an endpoint in clinical trial design, it is important to consider that the endpoint is both reliably measured and clinically meaningful. As such, overall survival (OS) has traditionally been considered the most clinically relevant and convincing endpoint in clinical trial design as long as it is accompanied by preservation in quality of life. However, progression-free survival (PFS) is increasingly more prominent in clinical trial design because of feasibility issues (smaller sample sizes and shorter follow-up). PFS has the advantage of taking into account not only responsive disease, but stable disease as well, an issue of particular importance in the relapsed and refractory setting in which therapies are often associated with a minimal to nil response but may still confer a survival advantage. Finally, PFS has a significant advantage in molecularly selected populations, in whom OS advantages are difficult to detect due to the effects of crossover. With an understanding of the limitations and biases that are introduced with PFS as a primary endpoint, we believe that PFS is not only a viable but also a necessary alternative to OS in assessing the efficacy of selected novel-targeted therapies in molecularly defined cancer populations. Ultimately, the selection of a clinical trial endpoint should not be based on a one-size-fits all approach; rather, it should be based on the specifics of the therapeutic strategy being tested and the population under study.