title: Predictive biomarkers in patients with resected non-small cell lung cancer treated with perioperative chemotherapy.
abstract: 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.
authors.affiliation: 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.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bergot
authors.forename: Guénaëlle
authors.initials: G
authors.lastname: Levallet
authors.forename: Karine
authors.initials: K
authors.lastname: Campbell
authors.forename: Fatéméh
authors.initials: F
authors.lastname: Dubois
authors.forename: Emmanuèle
authors.initials: E
authors.lastname: Lechapt
authors.forename: Gérard
authors.initials: G
authors.lastname: Zalcman
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011013:Pneumonectomy; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor