Service de Pneumologie et Oncologie Thoracique, CHU Côte de Nacre, Caen, 2 U1086 INSERM Cancers et Préventions, Faculty of Medicine de Caen, Caen, 3 Intergroupe Francophone de Cancérologie Thoracique (IFCT), Paris, and 4 Département d'Anatomie Pathologique et Laboratoire d'Histologie, CHU Côte de Nacre, Caen, France.
Eur Respir Rev. 2013 Dec;22(130):565-76. doi: 10.1183/09059180.00007113.
The aim of this article is to summarise the published data on prognostic and predictive biomarkers for early-stage non-small cell lung cancer (NSCLC), and discuss how to integrate them into clinical trials. Large phase III trials have been published in resected NSCLC with biomarkers identifying subsets of patients benefitting from perioperative chemotherapy. Initial findings of predictive implications for the DNA repair protein, ERCC1, were not confirmed in a larger series of patients due to the versatility of the commercially available monoclonal ERCC1 antibody. Prediction of survival by RRM1 tumour expression was not confirmed in a prospective phase III trial in 275 patients with stage IV disease, precluding its use in early-stage NSCLC. BRCA1 mRNA tumour content also failed to predict platinum resistance in 287 stage IV NSCLC patients included in a phase II trial, and the results of a similar trial in early-stage patients are still pending. Of the several cDNA gene expression studies in early-stage NSCLC with non-overlapping prognostic signatures, few have been replicated in independent cohorts for prognostic value, and none received external validation for predictive value. Therefore, use of biomarkers predicting chemotherapy efficacy still needs additional validation before becoming routine practice in oncogene-driven pan-negative NSCLC patients.
本文旨在总结早期非小细胞肺癌（NSCLC）的预后和预测生物标志物的已发表数据，并讨论如何将其纳入临床试验。在可切除的 NSCLC 中，已经发表了大型 III 期试验，生物标志物可确定从围手术期化疗中获益的患者亚组。由于商业上可获得的 ERCC1 单克隆抗体的多功能性，最初发现 ERCC1 等 DNA 修复蛋白具有预测意义的结果在更大系列的患者中未得到证实。在 275 例 IV 期疾病患者的前瞻性 III 期试验中，RRM1 肿瘤表达对生存的预测未得到证实，因此不能在早期 NSCLC 中使用。在 287 例 IV 期 NSCLC 患者的 II 期试验中，BRCA1 mRNA 肿瘤含量也未能预测铂类耐药，而早期患者的类似试验结果仍在等待中。在具有非重叠预后特征的早期 NSCLC 的几个 cDNA 基因表达研究中，很少有研究在独立队列中得到复制以验证其预后价值，也没有研究对预测价值进行外部验证。因此，预测化疗疗效的生物标志物在成为无致癌基因驱动的 pan-negative NSCLC 患者的常规治疗方法之前，仍需要进一步验证。
