Department of Regulatory Science, Faculty of Pharmacy, Meiji Pharmaceutical University, Kiyose-city, Tokyo, Japan.
Biostatistics Group, Data Science Department, Astellas Pharma Global Development, Inc, Northbrook, Illinois, USA.
Cancer Rep (Hoboken). 2021 Jun;4(3):e1334. doi: 10.1002/cnr2.1334. Epub 2021 Jan 17.
The purpose of this study was to investigate the correlation between overall survival (OS) and other clinical outcomes in patients with prostate cancer. Further, we conducted subgroup analysis in the correlation of OS.
This study intended to investigate potential surrogate endpoints of OS for prostate cancer by examining the correlation between OS and the other endpoints.
We performed a systematic review through a literature search by computer-based searches of the Medline database (January 1965 and May 2014).
The contents of 115 studies with endpoint as OS were analyzed in our study. Our results showed that 47.8% (55/115) of the studies used progression-free survival as an endpoint besides OS, followed by time to progression (43.5% [50/115]) and PSA response (40.9% [47/115]). Also, the relationship between OS and each surrogate endpoint was examined using the hazard ratio (HR) by a Bayesian hybrid model for random effect multivariate meta-analysis. Our results showed that the endpoint that had the highest correlation with OS was progression-free survival (PFS) with an estimated marginal correlation of 0.939 (95%CI: 0.900, 0.967). Furthermore, our stratified analysis identified PFS in castration-resistant prostate cancer patients (0.937), in sensitive patients (0.932), in none of chemotherapy patients (0.929), in first line of the chemotherapy (0.948), in patients who received no Docetaxel previously (0.942), in both symptomatic and asymptomatic patients (0.950), in patients who received only chemotherapy (0.956), and in phase III (0.960), time to progression (TTP) in castration-resistant prostate cancer (CRPC) patients (0.942), in metastasis patients (0.948), in both symptomatic and asymptomatic patients (0.953), in patients who received only chemotherapy (0.938), and in Phase III (0.927) as endpoints, which showed a lower limit for 95% CI of estimated marginal correlation ≥0.850 with overall survival.
Our study suggests that PFS is a potential surrogate endpoint of OS in clinical trials for patients with prostate cancer. It also suggests potential surrogate endpoints for CRPC and locally advanced prostate cancer.
本研究旨在探讨前列腺癌患者总生存（OS）与其他临床结局的相关性。此外，我们还对 OS 的相关性进行了亚组分析。
本研究通过探讨 OS 与其他终点的相关性，旨在寻找前列腺癌 OS 的潜在替代终点。
我们通过计算机检索 Medline 数据库（1965 年 1 月至 2014 年 5 月）进行系统评价。
本研究共分析了 115 项以 OS 为终点的研究内容。结果显示，47.8%（55/115）的研究除 OS 外还使用无进展生存期作为终点，其次是进展时间（43.5%[50/115]）和 PSA 反应（40.9%[47/115]）。此外，还使用贝叶斯混合模型进行随机效应多变量荟萃分析，通过危害比（HR）来检验 OS 与每个替代终点之间的关系。结果表明，与 OS 相关性最高的终点是无进展生存期（PFS），其估计边缘相关性为 0.939（95%CI：0.900，0.967）。此外，我们的分层分析确定了无进展生存期在去势抵抗性前列腺癌患者（0.937）、敏感患者（0.932）、无化疗患者（0.929）、一线化疗患者（0.948）、未接受多西他赛治疗的患者（0.942）、有症状和无症状患者（0.950）、仅接受化疗的患者（0.956）以及 III 期患者（0.960）中是与 OS 相关性最高的终点；在进展时间（TTP）中，去势抵抗性前列腺癌（CRPC）患者（0.942）、转移患者（0.948）、有症状和无症状患者（0.953）、仅接受化疗的患者（0.938）和 III 期患者（0.927）中是与 OS 相关性最高的终点，这些终点的估计边缘相关性的 95%CI 下限≥0.850。
本研究表明，PFS 是前列腺癌临床试验中 OS 的潜在替代终点，同时也为 CRPC 和局部晚期前列腺癌提供了潜在的替代终点。
Zotero 插件
