title: KRAS mutations affect prognosis of non-small-cell lung cancer patients treated with first-line platinum containing chemotherapy.
abstract: KRAS mutations seem to indicate a poor outcome in Non-Small-Cell Lung Cancer (NSCLC) but such evidence is still debated. The aim of this planned ancillary study within the TAILOR trial was to assess the prognostic value of KRAS mutations in advanced NSCLC patients treated with platinum-based first-line chemotherapy. Patients (N = 540), enrolled in the study in 52 Italian hospitals, were centrally genotyped twice in two independent laboratories for EGFR and KRAS mutational status.Of these, 247 patients were eligible and included in the present study. The primary endpoint was overall survival (OS) according to KRAS mutational status in patients harboring EGFR wild-type.Sixty (24.3%) out of 247 patients harbored KRAS mutations. Median OS was 14.3 months and 10.6 months in wild-type and mutated KRAS patients, respectively (unadjusted Hazard Ratio [HR]=1.41, 95%Confidence Interval [CI]: 1.03-1.94 P = 0.032; adjusted HR=1.39, 95%CI: 1.00-1.94 P = 0.050). This study, with all consecutive patients genotyped, indicates that the presence of KRAS mutations has a mild negative impact on OS in advanced NSCLC patient treated with a first-line platinum-containing regimen.
  
  
  BACKGROUND
  clinicaltrials.gov identifierNCT00637910.
authors.affiliation: Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Marabese
authors.affiliation: Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Ganzinelli
authors.affiliation: Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Marina C
authors.initials: MC
authors.lastname: Garassino
authors.affiliation: Princess Margaret Cancer Center, University of Toronto, Toronto, Canada.
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.affiliation: Oncology Department, Ospedale Fatebenefratelli e Oftalmico, Milan, Italy.
authors.forename: Sheila
authors.initials: S
authors.lastname: Piva
authors.affiliation: Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Caiola
authors.affiliation: Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Macerelli
authors.affiliation: Oncology Department, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bettini
authors.affiliation: Molecular Pathology Unit, Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan, Italy.
authors.forename: Calogero
authors.initials: C
authors.lastname: Lauricella
authors.affiliation: Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Floriani
authors.affiliation: Oncology Department, Ospedale Fatebenefratelli e Oftalmico, Milan, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Farina
authors.affiliation: Medical Oncology, Policlinico Umberto I, Rome, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Longo
authors.affiliation: Oncology Department, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Bonomi
authors.affiliation: Ospedale Belcolle, Viterbo, Italy.
authors.forename: M Agnese
authors.initials: MA
authors.lastname: Fabbri
authors.affiliation: Molecular Pathology Unit, Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Veronese
authors.affiliation: Clinical Trials Coordination Unit, Institute for Cancer Research and Treatment, IRCCS, Candiolo, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Marsoni
authors.affiliation: Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Broggini
authors.affiliation: Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Rulli
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010984:Platinum / Q000627:therapeutic use*; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; D010984:Platinum; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRAS; NSCLC; first-line; platinum