title: BE-POSITIVE: Beyond progression after tyrosine kinase inhibitor in EGFR- positive non small cell lung cancer patients: Results from a multicenter Italian observational study.
abstract: OBJECTIVE
  Non-small-cell-lung-cancer (NSCLC) patients harbouring epidermal growth factor receptor (EGFR) mutations develop drug resistance after 9-12 months of EGFR tyrosine kinase inhibitors (TKIs) therapy pointing out the issue of the second-line treatment choice.
  
  
  METHODS
  From June 2009 until May 2013 patients affected by advanced NSCLC harbouring EGFR mutations receiving first-line TKI were collected mainly retrospectively in 24 Italian Centers. Primary objective was to describe the percentage of EGFR mutated patients receiving second-line therapy after progression to first-line EGFR-TKIs assessing the type, the activity in terms of objective response rate (ORR), efficacy in terms of progression free survival (PFS) and overall survival (OS), and safety of second-line treatment. Secondary objective was to describe the efficacy of first-line EGFR-TKIs.
  
  
  RESULTS
  312 patients were included. Most of them were females (203, 65.1%), never smokers (200, 64.1%), with adenocarcinoma histology (290, 92.9%). The most common mutations were EGFR exon 19 deletion and L858R, detected in 186 and 97 cases (59.6% and 31.1%), respectively. At data cut-off, 274 patients (95.1%) received any second-line treatment (including best supportive care or local treatments only). A total of 163 patients received second-line systemic therapy with an ORR of 20.9% (95% CI:14.62-27.10), a median PFS and OS of 4.7 (95% CI:3.81-5.26) and 24.5 (95% CI:21.65-27.37) months, respectively. Grade 3-4 hematological and non-hematological toxicities were reported in 9% and 6.3% of 144 patients treated with chemotherapy while non-hematological toxicity was reported in 4 cases of the 17 patients receiving second-line target agents.
  
  
  CONCLUSIONS
  BE-Positive is the first multicenter observational study reporting outcomes of therapies in a "real-life Caucasian EGFR-mutated population", highlighting the need of further researches about new treatment strategies in this setting.
authors.affiliation: Department of Oncology, University of Torino AOU San Luigi, Regione Gonzole 10, 10043 Orbassano (TO), Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Vavalà
authors.affiliation: Department of Oncology, University Hospital of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Follador
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, via Gramsci, 14, 43126 Parma, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tiseo
authors.affiliation: Medical Oncology Unit, Clinical Cancer Center Giovanni Paolo II, viale Orazio Flacco, 65, 70124 Bari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Galetta
authors.affiliation: Thoracic Medical Oncology, National Cancer Institute, Fondazione "G.Pascale", via Mariano Semmola 80131, Napoli, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morabito
authors.affiliation: Clinical Trials Unit, National Cancer Institute, Fondazione "G.Pascale", via Mariano Semmola, 80131 Napoli, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Maio
authors.affiliation: Medical Oncology, S.Giovanni-Addolorata Hospital, via di S. Stefano Rotondo 5a, 00184 Roma, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Martelli
authors.affiliation: Medical Oncology Unit, Santa Chiara Hospital, Largo Medaglie D'oro 9, 38122 Trento, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Caffo
authors.affiliation: Medical Oncology Unit, AO SS. Antonio Biagio e Cesare Arrigo, via S. Pio V 5, Alessandria, Italy.
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Piovano
authors.affiliation: Medical Oncology Unit, AOU San Gerardo, via Giambattista Pergolesi 33, 20900 Monza, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Cortinovis
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, Milano, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Zilembo
authors.affiliation: Medical Oncology Unit, Valduce Hospital, via Dante Alighieri 11, 22100 Como, Italy.
authors.forename: Clelia
authors.initials: C
authors.lastname: Casartelli
authors.affiliation: Division of Medical Oncology, AO Cannizzaro Hospital, via Messina 829, 95126 Catania, Italy.
authors.forename: Giuseppe Luigi
authors.initials: GL
authors.lastname: Banna
authors.affiliation: Medical Oncology Unit, A.Manzoni Hospital via dell'Eremo 9/11, 23900 Lecco, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ardizzoia
authors.affiliation: AOU San Giovanni di Dio e Ruggi d' Aragona c/o P.O. G. da Procida, largo Città di Ippocrate, 84131 Salerno, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Barzelloni
authors.affiliation: Department of Medical Oncology, National Institute for Cancer Research, via Franco Gallini 2, Aviano (PN), Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bearz
authors.affiliation: Department of Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), via Piero Maroncelli 40, 47014 Meldola, Italy.
authors.forename: Giovenzio
authors.initials: G
authors.lastname: Genestreti
authors.affiliation: Department of Oncological Medicine, Ramazzini Hospital, via Guido Molinari 2, 41012 Carpi (MO), Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mucciarini
authors.affiliation: UOC Medical Oncology, AO Luigi Sacco, via Giovanni Battista Grassi 74, 20157 Milano,Italy.
authors.forename: Virginio
authors.initials: V
authors.lastname: Filipazzi
authors.affiliation: Department of Oncology, University Hospital of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Menis
authors.affiliation: EORTC Headquarters, Avenue E. Mounier 83, 1200 Bruxelles, Belgium.
authors.forename: Elisa
authors.initials: E
authors.lastname: Rizzo
authors.affiliation: Department of Oncology and Hemathology, AOU of Modena, viale del pozzo 71, Modena, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Barbieri
authors.affiliation: Lung Cancer Unit, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132 Genova, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Rijavec
authors.affiliation: Medical Oncology Unit, University Hospital Careggi, Largo Brambilla 3, 50134 Firenze, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Cecere
authors.affiliation: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata di Verona, P.zza L. A. Scuro 10, 37134 Verona, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.affiliation: Division of Thoracic Oncology, European Institute of Oncology, via Ripamonti 435, 20141 Milano, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Spitaleri
authors.affiliation: Division of Medical Oncology, S.G. Moscati Hospital, Contrada Amoretta Avellino, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Department of Oncology, University of Torino AOU San Luigi, Regione Gonzole 10, 10043 Orbassano (TO), Italy. Electronic address: silvia.novello@unito.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D006801:Humans; D007558:Italy; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019233:Retreatment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: Acquired resistance; EGFR mutation; EGFR tyrosine kinase inhibitors; First line; Non small cell lung cancer; Second line