Clinical and biomarker endpoint analysis in neoadjuvant endocrine therapy trials
Clinical and biomarker endpoint analysis in neoadjuvant endocrine therapy trials
复制标题
DOI：
10.1016/j.jsbmb.2005.04.017
复制
发表时间：
2005-05-01
影响因子：
4.1
通讯作者：
Ellis, M
中科院分区：
文献类型：
--
作者：
Tao, Y;Klause, A;Ellis, M
乳腺癌的新辅助内分泌治疗试验现在是肿瘤学合作组和制药公司研究计划广泛接受的研究方法。然而，关于这些研究最合适的终点仍存在相当大的不确定性，部分原因是短期临床、放射学或生物标志物缓解尚未完全验证为与长期乳腺癌结局密切相关的替代终点。在新辅助内分泌治疗可以用作旨在识别内分泌治疗“可治愈”疾病的患者的分诊策略之前，必须解决这一缺点。在本总结中，来自已发表研究的信息被用作评价临床试验设计的基础，并为未来的验证研究提出实验终点。新辅助内分泌治疗设计的三个方面被认为是：响应的确定;手术结果的评估;和生物标志物终点分析。来自来曲唑024（LET 024）试验的数据比较了来曲唑和他莫昔芬，用于说明整合临床和生物标志物信息的联合终点分析。此外，基于Ki 67分析，将“细胞周期应答”的概念作为一个简单的治疗后终点进行了探索，其可能具有与新辅助化疗试验中使用的病理学完全应答终点相似的性质。(c)2005爱思唯尔有限公司保留所有权利。
Neoadjuvant endocrine therapy trials for breast cancer are now a widely accepted investigational approach for oncology cooperative group and pharmaceutical company research programs. However, there remains considerable uncertainty regarding the most suitable endpoints for these studies, in part, because short-term clinical, radiological or biomarker responses have not been fully validated as surrogate endpoints that closely relate to long-term breast cancer outcome. This shortcoming must be addressed before neoadjuvant endocrine treatment can be used as a triage strategy designed to identify patients with endocrine therapy "curable" disease. In this summary, information from published studies is used as a basis to critique clinical trial designs and to suggest experimental endpoints for future validation studies. Three aspects of neoadjuvant endocrine therapy designs are considered: the determination of response; the assessment of surgical outcomes; and biomarker endpoint analysis. Data from the letrozole 024 (LET 024) trial that compared letrozole and tamoxifen is used to illustrate a combined endpoint analysis that integrates both clinical and biomarker information. In addition, the concept of a "cell cycle response" is explored as a simple post-treatment endpoint based on Ki67 analysis that might have properties similar to the pathological complete response endpoint used in neoadjuvant chemotherapy trials. (c) 2005 Elsevier Ltd. All rights reserved.