title: The comparison of outcomes from tyrosine kinase inhibitor monotherapy in second- or third-line for advanced non-small-cell lung cancer patients with wild-type or unknown EGFR status.
abstract: BACKGROUND
  Second-line treatment for advanced non-small-cell lung cancer (NSCLC) patients includes monotherapy with a third-generation cytotoxic drug (CT) or a tyrosine kinase inhibitor (TKI). These options are the actual standard for EGFR wild-type (WT) status, as patients with EGFR mutations achieve greater benefit by the use of TKI in first-line treatment. Some clinical trials and meta-analyses investigated the comparison between CT and TKI in second-line, but data are conflicting.
  
  
  METHODS
  We designed a retrospective trial to gather information about TKI sensitivity in comparison with CT. We selected from clinical records patients treated with at least 1 line of CT and at least 1 line of TKI. We collected data about age, sex, performance status, comorbidity, smoking status, histotype, metastatic sites, EGFR status, treatment schedule, better response and time-to-progression (TTP) for each line of treatment and overall survival (OS).
  
  
  RESULTS
  93 patients met selection criteria. Mean age 66,7 (range: 46-84). M/F ratio is 3:1. 39 EGFR-WT and 54 EGFR-UK. All patients received erlotinib or gefitinib as second-line treatment or erlotinib as third-line treatment. No TTP differences were observed for both second-line (HR:0,91; p = 0,6333) and third-line (HR:1.1; p = 0,6951) treatment (TKI vs CT). A trend of a benefit in OS in favor of 3rd-line TKI (HR:0,68; p = 0,11).
  
  
  CONCLUSIONS
  This study explores the role of TKIs in EGFR non-mutated NSCLC patients. OS analysis highlights a trend to a benefit in patients who received TKI in third-line, even if this result is statistically non-significant. Further analysis are needed to find an explanation for this observation.
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bronte
authors.affiliation: Medical Oncology Unit-AOOR Papardo-Piemonte, Messina and Department of Human Pathology, University of Messina, Messina, Italy.
authors.forename: Tindara
authors.initials: T
authors.lastname: Franchina
authors.affiliation: Medical Oncology Unit, A.R.N.A.S. Civico, Palermo, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Alù
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sortino
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Celesia
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Passiglia
authors.affiliation: Medical Oncology Unit, A.R.N.A.S. Civico, Palermo, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Savio
authors.affiliation: Medical Oncology Unit, A.R.N.A.S. Civico, Palermo, Italy.
authors.forename: Agata
authors.initials: A
authors.lastname: Laudani
authors.affiliation: Medical Oncology Unit-AOOR Papardo-Piemonte, Messina and Department of Human Pathology, University of Messina, Messina, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Russo
authors.affiliation: Medical Oncology Unit-AOOR Papardo-Piemonte, Messina and Department of Human Pathology, University of Messina, Messina, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Picone
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rizzo
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio", Chieti, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: De Tursi
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio", Chieti, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gambale
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Bazan
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio", Chieti, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Natoli
authors.affiliation: Medical Oncology Unit, A.R.N.A.S. Civico, Palermo, Italy.
authors.forename: Livio
authors.initials: L
authors.lastname: Blasi
authors.affiliation: Medical Oncology Unit-AOOR Papardo-Piemonte, Messina and Department of Human Pathology, University of Messina, Messina, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Adamo
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use; D005260:Female; D000077156:Gefitinib; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: EGFR; chemotherapy; non-small-cell lung cancer; tyrosine kinase inhibitor