1 European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium.
2 University Groningen, Groningen, the Netherlands.
J Clin Oncol. 2019 May 1;37(13):1102-1110. doi: 10.1200/JCO.18.01100. Epub 2019 Mar 12.
The mode of action of targeted cancer agents (TCAs) differs from classic chemotherapy, which leads to concerns about the role of RECIST in evaluating tumor response in trials with TCAs. We investigated the performance of RECIST using a pooled database from 50 clinical trials with at least one TCA.
We examined the impact of the number of target lesions (TLs) on within-patient variability of tumor response. The prognostic effect of TL response (at 12 weeks or on study on the basis of a maximum five TLs) on survival was studied through landmark and time-dependent Cox models adjusted for baseline tumor load, occurrence of new lesions, or unequivocal progression of nontarget disease.
Data were obtained from 23,259 patients with cancer (36% lung, 28% colorectal, 11% breast, and 25% other); 15,620 received TCAs, predominantly transduction or angiogenesis inhibitors, as a single agent (37%), combined with other TCAs (7%), or as chemotherapy (56%); 28% received chemotherapy only; and 5% received best supportive care or placebo. A total of 17,222 patients contributed to the analyses. Within-patient variability decreased with increasing number of TLs, similarly for TCAs (with/without chemotherapy) and chemotherapy only. Mixed responses occurred proportionally in all treatment classes. Landmark analyses showed an ordinal relationship between percentage change from baseline to 12 weeks and overall survival, and demonstrated a clear distinction between tumor shrinkage and progressive disease according to RECIST. Time-dependent analysis showed no marked improvement in the ability to predict survival on the basis of TL tumor growth compared with nontarget progression or new lesion occurrence, regardless of treatment. Similar results were seen for major tumor types and different classes of TCAs.
This work reinforces that RECIST version 1.1 perform well for response assessment of TCAs.
靶向抗癌药物（TCA）的作用模式与传统化疗不同，这引发了人们对 RECIST 在 TCA 试验中评估肿瘤反应的作用的担忧。我们通过至少包含一种 TCA 的 50 项临床试验的汇总数据库来研究 RECIST 的性能。
我们研究了靶病变（TL）数量对肿瘤反应患者内变异性的影响。通过基于最大 5 个 TL 的 12 周时或研究时的 TL 反应和基于基线肿瘤负荷、新病变发生或非目标疾病明确进展的 landmark 和时依 Cox 模型，研究 TL 反应对生存的预后影响。
该研究纳入了 23259 名癌症患者（36%为肺癌，28%为结直肠癌，11%为乳腺癌，25%为其他癌种）的数据；15620 名患者接受了 TCA 单药治疗（37%）、联合其他 TCA（7%）或联合化疗（56%），或接受了化疗（28%），还有 5%接受了最佳支持治疗或安慰剂。共有 17222 名患者参与了分析。TL 数量的增加与患者内变异性的降低有关，TCA（有/无化疗）和单纯化疗的情况均如此。所有治疗组中均有混合反应发生。 landmark 分析显示，从基线到 12 周的百分比变化与总生存之间存在有序关系，根据 RECIST 显示肿瘤缩小和疾病进展之间有明显区别。时间依赖性分析显示，无论治疗如何，TL 肿瘤生长与非目标进展或新病变发生相比，在预测生存方面的能力并无明显提高。在主要肿瘤类型和不同类别的 TCA 中也观察到了类似的结果。
这项研究强化了 RECIST 版本 1.1 可很好地评估 TCA 的反应。
