...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cancer chemotherapy and pharmacology. >Application of time-dependent modeling for the exposure-efficacy analysis of ceritinib in untreated ALK-rearranged advanced NSCLC patients
【24h】

Application of time-dependent modeling for the exposure-efficacy analysis of ceritinib in untreated ALK-rearranged advanced NSCLC patients

机译：时间依赖性建模在未处理的ALK重新安置高级NSCLC患者中Ceritinib曝光效果分析的应用

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Purpose Ceritinib 750 mg/day was approved for the treatment of patients with untreated anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) based on ASCEND-4 study. The objective of this article is to introduce the use of time-dependent modeling approach in the updated exposure-efficacy analysis of ceritinib for the first-line indication. Methods Exposure-efficacy analyses, including data from 156 patients, were first conducted using time-independent logistic regression model for response of complete or partial response and Cox regression model for progression-free survival (PFS). The exposure measure used was average C-trough, which is defined as the geometric mean of all evaluable C-trough for each patient. To further investigate the impact of exposure measure on exposure-efficacy analyses, a time-dependent modeling approach was used, where exposure at different time intervals was associated with the corresponding response endpoints in a longitudinal manner. Results With exposure measure being average C-trough, it was observed that higher exposure was associated with reduced efficacy in terms of response (odds ratio = 0.77) and PFS [hazard ratio (HR) = 1.12]. These time-independent models do not account for the impact of time-varying concentration due to dose modifications. Subsequently, a new time-dependent modeling approach was used, where exposure and efficacy were associated longitudinally in the analyses. The results showed that the odds ratio of response became 1.07, and the HR of PFS became 1.04, indicating no apparent reverse relationship between exposure and efficacy across the exposure range studied. Conclusion The drug effect on efficacy in clinical trials could be better characterized using time-dependent exposure-response models.
机译：目的，Ceritinib 750mg /天被批准用于治疗未处理的促进性淋巴瘤激酶（ALK） - 基于Ascend-4研究的非小细胞肺癌（NSCLC）。本文的目的是在Ceritinib的更新曝光效能分析中引入使用时间依赖性建模方法，以进行一线指示。方法采用时间无关的逻辑回归模型，首先使用时间无关的逻辑回归模型进行156名患者的曝光效率分析，以进行无进展生存（PFS）的完整或部分响应和COX回归模型的响应。使用的曝光措施是平均C-槽，其被定义为每个患者的所有评估C槽的几何平均值。为了进一步研究曝光措施对暴露效率分析的影响，使用了时间依赖性建模方法，其中不同时间间隔的暴露与相应的响应端点以纵向方式相关联。接触措施的结果是平均c-槽，观察到，在响应（差异= 0.77）和PFS [危险比（HR）= 1.12]中，较高的曝光与降低的疗效相关。这些时间无关的模型不考虑由于剂量修饰引起的时变浓度的影响。随后，使用新的时间依赖性建模方法，其中纵向地在分析中纵向接触和疗效。结果表明，响应的差异比为1.07，PFS的HR变为1.04，表明在研究的曝光范围内的暴露和功效没有明显的反向关系。结论使用时间依赖性暴露 - 反应模型，可以更好地表征临床试验中对临床试验的疗效的药物影响。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号