title: Value of KRAS as prognostic or predictive marker in NSCLC: results from the TAILOR trial.
abstract: BACKGROUND
  The prognostic and predictive role of KRAS mutations in advanced nonsmall-cell lung cancer (NSCLC) is still unclear. TAILOR prospectively assessed the prognostic and predictive value of KRAS mutations in NSCLC patients treated with erlotinib or docetaxel in second line.
  
  
  METHODS
  NSCLC patients from 52 Italian hospitals were genotyped for KRAS and EGFR mutational status in two independent laboratories. Wild-type EGFR patients (N = 218) received first-line platinum-based chemotherapy and were randomly allocated at progression to erlotinib or docetaxel. Overall survival (OS) according to KRAS mutational status was the primary end point.
  
  
  RESULTS
  KRAS mutations were present in 23% of TAILOR randomized cases. The presence of a KRAS mutation did not adversely affect progression-free (PFS) or overall (OS) survival [hazard ratio (HR) PFS = 1.01, 95% confidence interval (CI) 0.71-1.41, P = 0.977; OS = 1.24, 95% CI 0.87-1.77, P = 0.233], nor influenced treatment outcome (test for interaction: OS P = 0.965; PFS P = 0.417). Patients randomized to docetaxel treatment experienced longer survival independently from the KRAS mutational status of their tumors (HR: mutated KRAS 0.81, 95% CI 0.45-1.47; wild-type KRAS 0.79, 95% CI 0.57-1.10).
  
  
  CONCLUSIONS
  In TAILOR, KRAS was neither prognostic nor predictive of benefit for either docetaxel or erlotinib. Docetaxel remains superior independently from KRAS status for second-line treatment in EGFR wild-type advanced NSCLC patients.
  
  
  BACKGROUND
  NCT00637910.
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Milan.
authors.forename: E
authors.initials: E
authors.lastname: Rulli
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Milan.
authors.forename: M
authors.initials: M
authors.lastname: Marabese
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Milan.
authors.forename: V
authors.initials: V
authors.lastname: Torri
authors.affiliation: Department of Medical Oncology, Fatebenefratelli e Oftalmico Hospital, Milan.
authors.forename: G
authors.initials: G
authors.lastname: Farina
authors.affiliation: Department of Pathology, Niguarda Cancer Center, Ospedale Niguarda Cà Granda, Milan.
authors.forename: S
authors.initials: S
authors.lastname: Veronese
authors.affiliation: Department of Medical Oncology, Papa Giovanni XXIII Hospital, Bergamo.
authors.forename: A
authors.initials: A
authors.lastname: Bettini
authors.affiliation: Department of Medical Oncology, Università La Sapienza, Policlinico Umberto I, Rome.
authors.forename: F
authors.initials: F
authors.lastname: Longo
authors.affiliation: Department of Medical Oncology, Ospedale Belcolle, Viterbo.
authors.forename: L
authors.initials: L
authors.lastname: Moscetti
authors.affiliation: Thoracic Oncology Unit, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: M
authors.initials: M
authors.lastname: Ganzinelli
authors.affiliation: Department of Pathology, Niguarda Cancer Center, Ospedale Niguarda Cà Granda, Milan.
authors.forename: C
authors.initials: C
authors.lastname: Lauricella
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Milan.
authors.forename: E
authors.initials: E
authors.lastname: Copreni
authors.affiliation: Department of Medical Oncology, Papa Giovanni XXIII Hospital, Bergamo.
authors.forename: R
authors.initials: R
authors.lastname: Labianca
authors.affiliation: Department of Medical Oncology, Ospedale San Giovanni e Addolorata, Rome.
authors.forename: O
authors.initials: O
authors.lastname: Martelli
authors.affiliation: Clinical Trials Coordination Unit, Istituto di Candiolo-FPO, IRCCS, Candiolo, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Marsoni
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Milan massimo.broggini@marionegri.it.
authors.forename: M
authors.initials: M
authors.lastname: Broggini
authors.affiliation: Thoracic Oncology Unit, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: M C
authors.initials: MC
authors.lastname: Garassino
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000077143:Docetaxel; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D043823:Taxoids; D000077143:Docetaxel; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRAS; NSCLC; docetaxel; erlotinib