The Institute of Cancer Research, London, UK.
The Royal Marsden Hospital NHS Foundation Trust, London, UK.
Blood Cancer J. 2024 Aug 12;14(1):134. doi: 10.1038/s41408-024-01109-4.
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.
总生存期（OS）的测量仍然是解释 3 期试验中新疗法对多发性骨髓瘤影响的金标准。然而，随着结果的改善，如果要及时批准新的药物，以确保为患者带来最大的益处，那么将 OS 作为主要终点使用越来越具有挑战性。OS 的替代终点，如无进展生存期（PFS）和治疗反应，已被美国食品和药物管理局（FDA）和欧洲药品管理局（EMA）作为显示临床获益的终点纳入批准决策，FDA 最近还支持将微小残留病（MRD）作为多发性骨髓瘤的加速批准终点。本综述旨在讨论在何种情况下将 PFS 作为替代终点使用需要特别谨慎解释，尤其是对于特定亚组患者，并考虑如何确保可以设计研究以解决 PFS 和 OS 之间可能存在的差异。还讨论了亚组分析的效用，包括潜在的非预先指定的亚组分析，以确定新药物的目标人群。
