Progression-free survival is a surrogate for survival in advanced colorectal cancer
Progression-free survival is a surrogate for survival in advanced colorectal cancer
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DOI：
10.1200/jco.2007.11.8836
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发表时间：
2007-11-20
影响因子：
45.3
通讯作者：
Piedbois, Pascal
中科院分区：
文献类型：
--
作者：
Buyse, Marc;Burzykowski, Tomasz;Piedbois, Pascal
评估晚期癌症一线化疗疗效的传统终点是总生存期（OS），但该终点需要长期随访，并可能受到二线治疗效果的混淆。我们研究了无进展生存期（PFS）是否可以被认为是晚期结直肠癌OS的有效替代指标。患者和方法个体患者数据来自10项历史性试验，比较了氟尿嘧啶（FU）+甲酰四氢叶酸（leucovorin）与单独FU（1，744例患者）或雷替曲塞（1，345例患者）和3项比较FU +甲酰四氢叶酸联合或不联合伊立替康或奥沙利铂的验证试验（1，263例患者）。在历史试验中估计PFS和OS终点之间以及对这些终点的治疗效果之间的相关系数。治疗对OS的影响进行了预测验证试验，并与观察到的effects.Results相比，在历史试验中，1,760例（57%）已进展或死亡，在6个月，1,622（52%）已死亡，在12个月。PFS和OS之间的等级相关系数等于0.82（95% CI，0.82 - 0.83）。当考虑所有试验时，治疗对PFS和OS的影响之间的相关系数范围为0. 99（95% CI，0. 94 - 1. 04），排除一项高度影响力的试验后为0. 74（95% CI，0. 44 - 1. 04）。在验证试验中，观察到的OS风险比在95%预测区间内。PFS的风险比为0.77或更低将预测OS的获益。结论PFS是晚期结直肠癌OS的可接受替代指标。
Purpose The traditional end point for assessing efficacy of first-line chemotherapies for advanced cancer is overall survival (OS), but this end point requires prolonged follow-up and is potentially confounded by the effects of second-line therapies. We investigated whether progression-free survival (PFS) could be considered a valid surrogate for OS in advanced colorectal cancer.Patients and Methods Individual patient data were available from 10 historical trials comparing fluouracil (FU) + leucovorin with either FU alone (1,744 patients) or with raltitrexed (1,345 patients) and from three validation trials comparing FU + leucovorin with or without irinotecan or oxaliplatin (1,263 patients). Correlation coefficients were estimated in historical trials between the end points of PFS and OS, and between the treatment effects on these end points. Treatment effects on OS were predicted in validation trials, and compared with the observed effects.Results In historical trials, 1,760 patients (57%) had progressed or died at 6 months, and 1,622 (52%) had died at 12 months. The rank correlation coefficient between PFS and OS was equal to 0.82 (95% Cl, 0.82 to 0.83). The correlation coefficient between treatment effects on PFS and on OS ranged from 0.99 (95% Cl, 0.94 to 1.04) when all trials were considered to 0.74 (95% Cl, 0.44 to 1.04) after exclusion of one highly influential trial. In the validation trials, the observed OS hazard ratios were within the 95% prediction intervals. A hazard ratio of 0.77 or lower in terms of PFS would predict a benefit in terms of OS.Conclusion PFS is an acceptable surrogate for OS in advanced colorectal cancer.