Overall Response Rate, Progression-Free Survival, and Overall Survival With Targeted and Standard Therapies in Advanced Non-Small-Cell Lung Cancer: US Food and Drug Administration Trial-Level and Patient-Level Analyses
Overall Response Rate, Progression-Free Survival, and Overall Survival With Targeted and Standard Therapies in Advanced Non-Small-Cell Lung Cancer: US Food and Drug Administration Trial-Level and Patient-Level Analyses
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DOI：
10.1200/jco.2014.59.0489
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发表时间：
2015-03-20
影响因子：
45.3
通讯作者：
Pazdur, Richard
中科院分区：
文献类型：
--
作者：
Blumenthal, Gideon M.;Karuri, Stella W.;Pazdur, Richard
目的探讨晚期非小细胞肺癌（NSCLC）试验中总缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）在试验水平和患者水平上的相关性。方法：我们收集了自2003年以来提交给美国食品和药物管理局的14项晚期NSCLC治疗试验（N = 12567）。只纳入了150名以上患者的随机、主动对照试验。使用加权线性回归模型分析试验水平PFS风险比（HR）、OS HR和ORR比值比之间的关系。使用来自所有研究的汇总数据，对有和无客观反应的患者的PFS和OS进行患者级反应分析。结果在试验水平分析中，PFS与ORR之间有很强的相关性（R-2 = 0.89; 95% CI, 0.80 ~ 0.98）。OS与ORR （R-2 = 0.09; 95% CI, 0 ~ 0.33）、OS与PFS （R-2 = 0.08; 95% CI, 0 ~ 0.31）之间无关联。在患者水平的应答者分析中，与无应答者相比，获得应答的患者具有更好的PFS和OS （PFS: HR, 0.40; 95% CI， 0.38至0.42;OS: HR, 0.40; 95% CI， 0.38至0.43）。结论在试验水平上，ORR和PFS之间存在很强的相关性。ORR和OS之间以及PFS和OS之间的关联尚未确定，可能是因为靶向治疗和一线试验进展后的交叉和更长的生存期。患者水平分析显示，与无应答者相比，应答者有更好的PFS和OS。对ORR有较大影响的晚期NSCLC治疗可能具有较大的PFS效应。(C) 2015年由美国临床肿瘤学会出版
PurposeTo conduct analyses exploring trial-level and patient-level associations between overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) trials.MethodsWe identified 14 trials (N = 12,567) submitted to US Food and Drug Administration since 2003 of treatments for advanced NSCLC. Only randomized, active-controlled trials with more than 150 patients were included. Associations between trial-level PFS hazard ratio (HR), OS HR, and ORR odds ratio were analyzed using a weighted linear regression model. Patient-level responder analyses comparing PFS and OS between patients with and without an objective response were performed using pooled data from all studies.ResultsIn the trial-level analysis, the association between PFS and ORR was strong (R-2 = 0.89; 95% CI, 0.80 to 0.98). There was no association between OS and ORR (R-2 = 0.09; 95% CI, 0 to 0.33) and OS and PFS (R-2 = 0.08; 95% CI, 0 to 0.31). In the patient-level responder analyses, patients who achieved a response had better PFS and OS compared with nonresponders (PFS: HR, 0.40; 95% CI, 0.38 to 0.42; OS: HR, 0.40; 95% CI, 0.38 to 0.43).ConclusionOn a trial level, there is a strong association between ORR and PFS. An association between ORR and OS and between PFS and OS was not established, possibly because of cross-over and longer survival after progression in the targeted therapy and first-line trials. The patient-level analysis showed that responders have a better PFS and OS compared with nonresponders. A therapy in advanced NSCLC with a large magnitude of effect on ORR may have a large PFS effect. (C) 2015 by American Society of Clinical Oncology