Relationship between effects on time-to-disease progression and overall survival in studies of metastatic breast cancer
Relationship between effects on time-to-disease progression and overall survival in studies of metastatic breast cancer
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DOI：
10.1038/sj.bjc.6604759
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发表时间：
2008-11-11
影响因子：
8.8
通讯作者：
Cuzick, J.
中科院分区：
文献类型：
--
作者：
Sherrill, B.;Amonkar, M.;Cuzick, J.
总生存期（OS）与疾病进展终点之间的关系已在结直肠癌、结肠癌和非小细胞肺癌中得到证实。我们评估了转移性乳腺癌（MBC）研究中OS与进展时间（TTP）或无进展生存期（PFS）之间的关系。文献检索检索了1994年以来所有报道有OS和TTP或PFS的MBC患者的随机对照试验。总结试验数据和患者特征。研究效应大小由中位进展（或生存）时间的比值得出，该比值近似于风险比。在按样本量加权的回归分析中，效应以零为中心。67项研究（17,081例患者）采用了多种治疗方法。模型显示进展和生存之间的结果呈正相关（R-2=0.30），斜率为0.32 (P < 0.001)，截距无显著性。因此，治疗对TTP/ PFS的影响转化为对OS的一致影响，但效应大小减弱。在子集模型和敏感性分析中也发现了类似的结果。这些结果表明，在MBC试验中，治疗对进展终点的影响预计会导致OS的治疗差异较小，但在同一方向上保持一致。
The relationship between overall survival ( OS) and disease progression end points has been demonstrated in colorectal, colon, and non-small cell lung cancers. We assessed the association between OS and time-to-progression (TTP) or progression-free survival (PFS) in metastatic breast cancer (MBC) studies. A literature search retrieved all randomised controlled trials since 1994 in patients with MBC in which OS and either TTP or PFS were reported. Summary data on trial and patient characteristics were abstracted. Study effect sizes were derived as the ratio of median progression ( or survival) times, which approximates the hazard ratio. Effects were centred at zero for regression analyses weighted by sample size. Numerous treatments were represented in 67 studies ( 17 081 patients). Modeling showed a positive association between outcomes for progression and survival (R-2=0.30) with a slope of 0.32 (P < 0.001) and a non-significant intercept. Thus, a treatment effect on TTP/ PFS translated into a concordant effect on OS, but with attenuated effect size. Similar results were found in models of subsets and sensitivity analyses. These results demonstrate that treatment effects on progression end points in MBC trials are expected to result in treatment differences on OS that are smaller yet consistently in the same direction.