评估代理终点和瘤学临床试验的整体存活率之间的相关性
Guotao Chu1, Xiaochen Zhu1, Jiaju Wu1
1Global Biometrics & Data Sciences, Bristol Myers Squibb, Princeton, New Jersey, USA.
Clinical pharmacology and therapeutics
|February 27, 2025
概括
在癌症试验中,无进展生存率 (PFS) 是一个比客观反应率 (ORR) 更可靠的替代终点,用于总生存率 (OS). 免疫瘤疗法和一线治疗显示出更强的相关性.
科学领域:
- 在瘤学瘤学.
- 临床试验 临床试验
- 生物统计学 生物统计学
背景情况:
- 像PFS和ORR这样的替代终点加速了瘤学药物开发.
- 它们在预测整体存活率 (OS) 上的有效性需要严格的验证.
- 来自布里斯托尔·迈尔斯·斯奎布 (Bristol Myers Squibb) 的综合数据集被用于全面分析.
研究的目的:
- 评估代用终点 (PFS,ORR) 和OS之间的相关性.
- 评估各种癌症类型,治疗和治疗线的终点可靠性.
- 为了比较替代终点验证的患者级和试验级的相关性.
主要方法:
- 来自布里斯托尔·迈尔斯·斯奎布的综合数据集的分析.
- 在患者和试验层面评估PFS,ORR和OS之间的相关性.
- 检查不同癌症类型,治疗 (化疗与IO) 和治疗线 (第一线与后一线) 的相关性.
主要成果:
- 患者层面:PFS与OS的相关性比最佳整体反应 (BOR) 更强.
- 黑色素瘤患者的OS-BOR相关性最高;IO治疗患者的相关性比化疗更强.
- 与后来的线路相比,第一线治疗患者在BOR,PFS和OS之间表现出更强的相关性.
- 试验水平:PFS危险比率 (HR) 和ORR差异 (∆ORR) 显示出最强的相关性.
- 黑色素瘤和IO治疗研究表明了一致和显著的相关性.
结论:
- 在瘤学试验中,PFS似乎是OS的更可靠的替代终点,而不是BOR.
- 相关性受癌症类型,治疗方式 (IO与化疗) 和治疗线的影响.
- 对PFSHR和∆ORR的试验级分析提供了替代终点有效性的强有力的验证.
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