Hematology and Oncology Department, Saarland University Hospital, Kirrberger Street 100, 66421, Homburg, Germany.
Oncology Service, Geneva University Hospital, 4 Gabrielle-Perret-Gentil Street, 1205, Geneva, Switzerland.
Eur J Cancer. 2024 May;202:114022. doi: 10.1016/j.ejca.2024.114022. Epub 2024 Mar 20.
Kaplan-Meier analysis hinges on the assumption that patients who are censored- lost to follow-up, or only recently enrolled on the study- are no different, on average, than patients who are followed. As such, censoring these patients- omitting their future information and taking the average of those who were followed- should not dramatically change the overall estimate. Yet, in a recent clinical trial, two sets of censoring rules- one favored by trialists and one favored by the US Food and Drug Administration- were applied to a progression-free survival (PFS) estimate. In response, the PFS estimate changed dramatically, increasing the median in the experimental arm from 32 to 43 months, while the control arm was essentially unchanged. In this commentary, we explore the reasons why PFS changed so dramatically. We provide a broad overview of censoring in oncology clinical trials, and suggestions to ensure that PFS is a more reliable endpoint.
Kaplan-Meier 分析取决于这样的假设,即被删失的患者——失访或仅最近入组研究——在平均水平上与被随访的患者没有区别。因此,对这些患者进行删失——忽略他们的未来信息并取随访患者的平均值——不应该显著改变总体估计。然而,在最近的一项临床试验中,两种删失规则——一种受到试验者的青睐,另一种受到美国食品和药物管理局的青睐——被应用于无进展生存期(PFS)估计。作为回应,PFS 估计发生了显著变化,使实验组的中位数从 32 个月增加到 43 个月,而对照组基本不变。在这篇评论中,我们探讨了 PFS 变化如此之大的原因。我们提供了肿瘤学临床试验中删失的广泛概述,并提出了确保 PFS 成为更可靠终点的建议。