Tang Patricia A, Bentzen Søren M, Chen Eric X, Siu Lillian L
Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, Canada.
J Clin Oncol. 2007 Oct 10;25(29):4562-8. doi: 10.1200/JCO.2006.08.1935. Epub 2007 Sep 17.
Our aims were to determine the correlations between progression-free survival (PFS), time to progression (TTP), and response rate (RR) with overall survival (OS) in the first-line treatment of metastatic colorectal cancer (MCRC), and to identify a potential surrogate for OS.
Randomized trials of first-line chemotherapy in MCRC were identified, and statistical analyses were undertaken to evaluate the correlations between the end points.
Thirty-nine randomized controlled trials were identified containing a total of 87 treatment arms. Among trials, the nonparametric Spearman rank correlation coefficient (r(s)) between differences (Delta) in surrogate end points (DeltaPFS, DeltaTTP, and DeltaRR) and DeltaOS were 0.74 (95% CI, 0.47 to 0.88), 0.52 (95% CI, 0.004 to 0.81), 0.39 (95% CI, 0.08 to 0.63), respectively. The r(s) for DeltaPFS was not significantly different from the r(s) DeltaTTP (P = .28). Linear regression analysis was performed using hazard ratios for PFS and OS. There was a strong relationship between hazard ratios for PFS and OS; the slope of the regression line was 0.54 +/- 0.10, indicating that a novel therapy producing a 10% risk reduction for PFS will yield an estimated 5.4% +/- 1% risk reduction for OS.
In first-line chemotherapy trials for MCRC, improvements in PFS are strongly associated with improvements in OS. In this patient population, PFS may be an appropriate surrogate for OS. As a clinical end point, PFS offers increased statistical power at a given time of analysis and a significant lead time advantage compared with OS.
我们的目的是确定转移性结直肠癌（MCRC）一线治疗中无进展生存期（PFS）、疾病进展时间（TTP）和缓解率（RR）与总生存期（OS）之间的相关性，并确定一个潜在的OS替代指标。
识别MCRC一线化疗的随机试验，并进行统计分析以评估终点之间的相关性。
识别出39项随机对照试验，共包含87个治疗组。在这些试验中，替代终点差异（DeltaPFS、DeltaTTP和DeltaRR）与DeltaOS之间的非参数Spearman等级相关系数（r(s)）分别为0.74（95%CI，0.47至0.88）、0.52（95%CI，0.004至0.81）、0.39（95%CI，0.08至0.63）。DeltaPFS的r(s)与DeltaTTP的r(s)无显著差异（P = 0.28）。使用PFS和OS的风险比进行线性回归分析。PFS和OS的风险比之间存在很强的关系；回归线的斜率为0.54±0.10，表明一种使PFS风险降低10%的新疗法将使OS风险估计降低5.4%±1%。
在MCRC一线化疗试验中，PFS的改善与OS的改善密切相关。在该患者群体中，PFS可能是OS的一个合适替代指标。作为一个临床终点，与OS相比，PFS在给定的分析时间提供了更高的统计效力和显著的提前期优势。
