title: Clinical and molecular features in patients with advanced non-small-cell lung carcinoma refractory to first-line platinum-based chemotherapy.
abstract: Most of the cases of non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage and are treated with platinum-doublet chemotherapy. However, some patients are refractory to this treatment. The aim of this study was to identify the clinical and molecular characteristics of patients with refractory disease. All consecutive patients between 2003 and 2006, who received a platinum-doublet chemotherapy as first-line treatment for stage IIIb-IV NSCLC, were included. Refractory patients were defined as early progressive disease (PD) at the first evaluation of chemotherapy according to WHO criteria. The clinical, histo-pathological, and molecular characteristics (EGFR: exon 19, 20, 21 and KRAS: exon 2 by PCR sequencing; ALK by immunohistochemistry) and survival of refractory patients with initial PD (r-patients) and controlled disease (c-patients) were compared by univariate analyses. Factors that differed between the two groups (p-value <0.25 in univariate analyses) were entered into multivariate analysis. In this study, 178 patients were included. The first tumor assessment was carried out after a median of three cycles (range 1-4). Forty-six (25.8%) patients were refractory. Clinical presentation was similar between r- and c-patients. The sarcomatoid histological subtype was more common in r-patients than c-patients (10.9% vs. 1.5%, respectively; p=0.057). The proportion of EGFR (5.2% vs. 9.6%, p=0.224) and KRAS mutations (11.1% vs. 5.7%, p=0.357), and the expression of ALK (6.3% vs. 2.5%, p=0.327) did not differ significantly between the two groups. In multivariate analysis, sarcomatoid histological subtype was the only factor associated with early PD (OR=7.50; 95%CI: 1.02-55.45; p=0.048). r-Patients had significantly shorter survival than c-patients (median 5 months (IQR 3.2-9.9) vs. 15.4 months (IQR 9.9-22.5), respectively; p<0.0001). In conclusion, patients with early PD under platinum-doublet chemotherapy had shorter survival than c-patients. Sarcomatoid histological subtype was the only independent factor associated with early PD.
authors.affiliation: Equipe de Recherche 2, "Interactions des cellules tumorales et leur environnement et résistance aux agents anticancéreux", GRC Université Paris 6 Pierre et Marie Curie Theranoscan, Hôpital Tenon - APHP, 4 rue de la Chine, 75970 Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Giroux Leprieur
authors.forename: M
authors.initials: M
authors.lastname: Antoine
authors.forename: T
authors.initials: T
authors.lastname: Vieira
authors.forename: M
authors.initials: M
authors.lastname: Duruisseaux
authors.forename: V
authors.initials: V
authors.lastname: Poulot
authors.forename: N
authors.initials: N
authors.lastname: Rabbe
authors.forename: L
authors.initials: L
authors.lastname: Belmont
authors.forename: V
authors.initials: V
authors.lastname: Gounant
authors.forename: A
authors.initials: A
authors.lastname: Lavolé
authors.forename: B
authors.initials: B
authors.lastname: Milleron
authors.forename: R
authors.initials: R
authors.lastname: Lacave
authors.forename: J
authors.initials: J
authors.lastname: Cadranel
authors.forename: M
authors.initials: M
authors.lastname: Wislez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics; D005091:Exons; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D017239:Paclitaxel / Q000008:administration & dosage; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D018631:ras Proteins / Q000235:genetics; D000093542:Gemcitabine
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine