文章：

无进展生存期作为骨髓瘤临床试验替代终点：不断演变的范式

Progression-free survival as a surrogate endpoint in myeloma clinical trials: an evolving paradigm

原文发布日期：2024-08-12

DOI: 10.1038/s41408-024-01109-4

类型: Review Article

开放获取: 是

英文摘要：

Measurement of overall survival (OS) remains the gold standard for interpreting the impact of new therapies for multiple myeloma in phase 3 trials. However, as outcomes have improved, it is increasingly challenging to use OS as the primary endpoint if timely approval of novel agents is to be ensured to enable maximum benefit for patients. Surrogate endpoints of OS, such as progression-free survival (PFS) and response to treatment, have contributed to approval decisions by the Food and Drug Administration (FDA) and European Medicines Agency as endpoints demonstrating clinical benefit, and the FDA has recently supported the use of minimal residual disease (MRD) as an accelerated approval endpoint in multiple myeloma. This review aims to address situations in which the use of PFS as a surrogate endpoint warrants careful interpretation especially for specific subgroups of patients and considers ways to ensure that studies can be designed to account for possible discordance between PFS and OS. The utility of subgroup analyses, including the potential for those not pre-specified, to identify target populations for new agents is also discussed.
 

摘要翻译： 

在3期临床试验中，总生存期（OS）的测量仍是评估新疗法对多发性骨髓瘤影响的金标准。然而，随着治疗效果的提升，若需确保新药及时获批以使患者获得最大获益，将OS作为主要终点正变得日益困难。OS的替代终点——如无进展生存期（PFS）和治疗反应——已被美国食品药品监督管理局（FDA）及欧洲药品管理局用于支持临床获益的审批决策；FDA近期还支持将微小残留病（MRD）作为多发性骨髓瘤的加速审批终点。本文旨在探讨在哪些情况下需谨慎解读以PFS作为替代终点的结果，尤其是针对特定患者亚群，并思考如何通过研究设计来协调PFS与OS可能存在的差异。文中还讨论了亚组分析（包括非预设亚组分析）在识别新药目标人群中的应用价值。

原文链接：

Progression-free survival as a surrogate endpoint in myeloma clinical trials: an evolving paradigm