Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
Department of Biomedical Engineering, University of California Davis, Davis, CA, USA.
Ann Surg Oncol. 2017 Aug;24(8):2371-2378. doi: 10.1245/s10434-017-5826-2. Epub 2017 Apr 10.
Overall survival (OS) has traditionally been the primary end point in studies evaluating the clinical benefit of first-line chemotherapy in metastatic, locally advanced, or unresectable pancreatic cancer (MLAUPC). Given the prolonged follow-up assessment required to obtain OS and its potential to be confounded by second-line treatments, this study sought to determine whether progression-free survival (PFS), response rate (RR), or disease control rate (DCR) can serve as a reliable surrogate for OS.
A systematic review and meta-analysis was performed including all phase 3 clinical trials for MLAUPC, with gemcitabine as the control arm of the trial. The hazard ratios (HRs) for OS and PFS and odds ratios (ORs) for RR and DCR were recorded. A weighted Pearson correlation coefficient was estimated for the association between OS and the other outcomes. The primary analysis used a random effects weighting model, whereas the secondary analyses used a fixed effects- or sample size-weighted approach.
For the study, 24 randomized controlled trials were identified. The Pearson correlation coefficient between OS and PFS was 0.86 (95% confidence interval [CI] 0.67-0.94; p < 0.001). Sensitivity analysis of the studies with little to no crossover further showed a correlation coefficient of 0.91 (95% CI 0.76-0.97; p < 0.001). The correlation coefficient between OS and RR was 0.45 (95% CI 0.07-0.72; p = 0.02) and between OS and DCR was 0.74 (95% CI 0.38-0.90; p < 0.001).
First-line chemotherapy trials for MLAUPC show a robust correlation between OS and PFS, affirming its role as a surrogate of OS.
在评估转移性、局部晚期或不可切除的胰腺癌（MLAUPC）一线化疗的临床获益的研究中，总生存期（OS）一直是主要终点。鉴于获得 OS 需要进行长期随访评估，并且可能会受到二线治疗的影响，本研究旨在确定无进展生存期（PFS）、缓解率（RR）或疾病控制率（DCR）是否可以作为 OS 的可靠替代指标。
进行了一项系统评价和荟萃分析，纳入了所有以吉西他滨为试验对照臂的 MLAUPC 三期临床试验。记录 OS 和 PFS 的风险比（HR）以及 RR 和 DCR 的优势比（OR）。使用加权 Pearson 相关系数估计 OS 与其他结局之间的关联。主要分析使用随机效应加权模型，而次要分析使用固定效应或样本量加权方法。
研究共纳入 24 项随机对照试验。OS 与 PFS 之间的 Pearson 相关系数为 0.86（95%置信区间 [CI] 0.67-0.94；p<0.001）。对几乎没有交叉的研究进行敏感性分析，进一步显示相关系数为 0.91（95% CI 0.76-0.97；p<0.001）。OS 与 RR 之间的相关系数为 0.45（95% CI 0.07-0.72；p=0.02），OS 与 DCR 之间的相关系数为 0.74（95% CI 0.38-0.90；p<0.001）。
MLAUPC 的一线化疗试验中，OS 与 PFS 之间存在很强的相关性，证实了 PFS 作为 OS 替代指标的作用。
