Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.
Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
Leuk Lymphoma. 2023 Feb;64(2):273-282. doi: 10.1080/10428194.2022.2136947. Epub 2022 Oct 25.
We systematically evaluated the primary and secondary endpoints used in acute myeloid leukemia (AML) phase III randomized controlled trials (RCTs). We included 238 phase III AML RCTs in the past 15 years that reported 279 primary endpoints and 657 secondary endpoints. Overall survival (OS), progression-free survival (PFS), event-free survival (EFS), and complete remission (CR) were primary endpoints in 120 (43%), 34 (12%), 30 (11%), and 41 (15%) studies, respectively. OS (12.5%), PFS (13.2%), CR (14%), safety (11%), and EFS (9%) were commonly reported secondary endpoints. Among primary endpoints, a higher use of OS (OR 2.03, 95%CI 1.10-3.75, = 0.023) and lower use of PFS (OR 0.25, 95%CI 0.12-0.52, < 0.001) was observed from 2014 to 2021 compared to 2006-2013; CR was frequently used in relapsed/refractory compared to frontline RCTs (OR 2.20, 95%CI 1.11-4.38, = 0.025); EFS was frequently used in frontline compared to relapsed/refractory AML RCTs (OR 10.11, 95%CI 1.34-76.34, = 0.025). A higher trend in the use of clinically meaningful and objective endpoint of OS over the last 15 years.
我们系统地评估了过去 15 年中用于急性髓系白血病（AML）III 期随机对照试验（RCT）的主要和次要终点。我们纳入了 238 项 III 期 AML RCT，这些研究报告了 279 个主要终点和 657 个次要终点。总生存期（OS）、无进展生存期（PFS）、无事件生存期（EFS）和完全缓解（CR）分别是 120 项（43%）、34 项（12%）、30 项（11%）和 41 项（15%）研究的主要终点。OS（12.5%）、PFS（13.2%）、CR（14%）、安全性（11%）和 EFS（9%）是常用的次要终点。在主要终点中，与 2006-2013 年相比，2014 年至 2021 年 OS（OR 2.03，95%CI 1.10-3.75， = 0.023）的使用频率更高，而 PFS（OR 0.25，95%CI 0.12-0.52， < 0.001）的使用频率更低；与复发/难治性 RCT 相比，CR 更常用于一线 RCT（OR 2.20，95%CI 1.11-4.38， = 0.025）；EFS 更常用于一线 AML RCT 相比复发/难治性 AML RCT（OR 10.11，95%CI 1.34-76.34， = 0.025）。在过去 15 年中，OS 这一具有临床意义和客观的终点的使用呈上升趋势。
