title: Effectiveness of erlotinib treatment in advanced KRAS mutation-negative lung adenocarcinoma patients: Results of a multicenter observational cohort study (MOTIVATE).
abstract: OBJECTIVE
  Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI), used for the treatment of non-small cell lung cancer. As the clinical significance of KRAS mutational status has not yet been clearly determined in this setting, our aim was to investigate the efficacy of erlotinib in advanced KRAS mutation-negative lung adenocarcinoma patients.
  
  
  METHODS
  MOTIVATE is an open-label, multicenter, observational trial with Tarceva(®) (erlotinib) monotherapy. Enrolled patients with advanced (stage IIIB/IV) KRAS wild type (WT) lung adenocarcinoma refractory to one or two courses of prior chemotherapy were treated with erlotinib at 150mg/day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and best tumor response rate (RR).
  
  
  CONCLUSIONS
  In total, 327 patients were included. Median PFS and OS were 3.3 and 14.4 months, respectively. Three patients (1.2%) had complete response, 51 patients (20.2%) had partial response and 123 patients (48.8%) had SD. Significantly longer median PFS and OS were observed in Eastern Oncology Cooperative Group Performance Status (ECOG PS) 0-1 patients, as compared to ECOG PS 2-3 patients. The longest median OS (20.5 months) was found in patients with ECOG PS 0-1 who received erlotinib as a second-line therapy. There was no difference in median OS in cohorts stratified to disease stage and smoking status. Female patients had both longer median PFS and OS. Disease control rate was 70.2%. Our results suggest that erlotinib represents a valid treatment option for patients with KRAS WT lung adenocarcinoma and, moreover, that KRAS mutation analysis could help to identify clinically relevant subgroups of NSCLC patients that may benefit from EGFR-TKI therapy.
authors.affiliation: Department of Respiratory Medicine, I. Internal Medicine, Medical University, Ifjúság út 13, 7624 Pécs, Hungary.
authors.forename: Veronika
authors.initials: V
authors.lastname: Sarosi
authors.affiliation: Department of Pulmonology, Semmelweis University, Diósárok utca 1/C, 1125 Budapest, Hungary.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Losonczy
authors.affiliation: National Koranyi Institute of TB and Pulmonology, Pihenő út 1, 1121 Budapest, Hungary.
authors.forename: Eva
authors.initials: E
authors.lastname: Francovszky
authors.affiliation: Klinik für Onkologie und Palliativmedizin, Helios-Klinikum-Aue, Gartenstr. 6, 08280 Aue Sachsen, Germany.
authors.forename: Edina
authors.initials: E
authors.lastname: Tolnay
authors.affiliation: National Koranyi Institute of TB and Pulmonology, Pihenő út 1, 1121 Budapest, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Torok
authors.affiliation: Department of Pulmonology, Semmelweis University, Diósárok utca 1/C, 1125 Budapest, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Galffy
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria; MTA-SE Tumor Progression Research Group, Hungarian Academy of Sciences, Üllői út 93, 1091 Budapest, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Hegedus
authors.affiliation: National Koranyi Institute of TB and Pulmonology, Pihenő út 1, 1121 Budapest, Hungary; Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria; Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Ráth György u. 7-9, 1122 Budapest, Hungary. Electronic address: balazs.dome@meduniwien.ac.at.
authors.forename: Balazs
authors.initials: B
authors.lastname: Dome
authors.affiliation: Department of Pulmonology, Semmelweis University, Diósárok utca 1/C, 1125 Budapest, Hungary. Electronic address: ostoros@koranyi.hu.
authors.forename: Gyula
authors.initials: G
authors.lastname: Ostoros
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D000069347:Erlotinib Hydrochloride; D005260:Female; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride
keywords: EGFR; Erlotinib; KRAS; Lung adenocarcinoma; Mutation status; Non-small cell lung cancer