Response rate or time to progression as predictors of survival in trials of metastatic colorectal cancer or non-small-cell lung cancer: a meta-analysis
Response rate or time to progression as predictors of survival in trials of metastatic colorectal cancer or non-small-cell lung cancer: a meta-analysis
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DOI：
10.1016/s1470-2045(06)70800-2
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发表时间：
2006-09-01
期刊：
影响因子：
51.1
通讯作者：
Ward, Robyn L.
中科院分区：
文献类型：
--
作者：
Johnson, Kent R.;Ringland, Clare;Ward, Robyn L.
如果使用替代终点代替生存期，癌症临床试验的持续时间和成本可以减少。我们进行了一项荟萃分析，以评估肿瘤缓解和进展时间这两个替代指标在多大程度上预测转移性结直肠癌和非小细胞肺癌的死亡率。（至进展的中位时间，对治疗有反应的患者比例，和中位总生存期），这些数据来自结肠直肠癌（146项试验）和肺癌（191项试验）一线治疗的随机试验。提取数据并通过线性回归进行分析。我们使用250，500和750例患者的试验预测带，以确定替代阈值效应，将预测一个显着的差异survival.Findings治疗反应和进展时间与改善生存期肺癌（p < 0.0001和p=0.0003，分别）和结直肠癌（p < 0.0001）。为了预测结直肠癌试验中显著的生存率增加，在750例患者的试验中，治疗应答的患者数量需要增加20%，在500例患者的试验中增加到26%，在250例患者的试验中增加到38%。在肺癌试验中，同样的预测需要750例患者的反应差异为18%，500例患者为21%，250例患者为30%。对于两种癌症类型的进展时间，预测生存改善所需的增量增益的中位数为1.8个月，750例患者的试验，2.2个月为500例患者，和3.3个月为250 patients.Interpretation无论试验规模，肿瘤反应率的巨大差异需要预测一个显着的生存获益。如果在临床试验中选择替代物作为主要终点，则进展时间是优选的测量，因为为了显著的存活益处需要更适度和可实现的差异。转移性肺癌和结直肠癌的试验应将生存率作为其主要结局指标，除非替代结局差异预计超过阈值效应量。
Background The duration and cost of cancer clinical trials could be reduced if a surrogate endpoint were used in place of survival. We did a meta-analysis to assess the extent to which two surrogates, tumour response and time to progression, are predictive of mortality in metastatic colorectal cancer and non-small-cell lung cancer.Methods Summary data (median time to progression, proportion of patients responding to treatment, and median overall survival) from randomised trials of first-line treatment in colorectal cancer (146 trials) and lung cancer (191 trials) were identified. Data were extracted and analysed by linear regression. We used prediction bands for trials with 250, 500, and 750 patients to identify the surrogate threshold effect that would predict a significant difference in survival.Findings Response to treatment and time to progression correlated with improvement in survival for both lung cancer (p < 0.0001 and p=0.0003, respectively) and colorectal cancer (p < 0.0001 for both). To predict a significant survival gain in colorectal cancer trials, an improvement of 20% in the number of patients responding to treatment was required in trials with 750 patients, increasing to 26% in trials with 500 patients and 38% in trials with 250 patients. In lung cancer trials, the same prediction required differences in response of 18% for 750 patients, 21% for 500 patients, and 30% for 250 patients. For time to progression for both cancer types, the incremental gain needed to predict a survival improvement was a median of 1.8 months for trials with 750 patients, 2.2 months for 500 patients, and 3.3 months for 250 patients.Interpretation Irrespective of trial size, large differences in tumour response rate are needed to predict a significant survival benefit. if surrogates are chosen as the primary endpoint in a clinical trial, time to progression is the preferred measure because more modest and achievable differences are needed for a significant survival benefit. Trials in metastatic lung cancer and colorectal cancer should measure survival as their primary outcome unless the surrogate outcome difference is anticipated to exceed the threshold effect size.