title: Clinical outcome with platinum-based chemotherapy in patients with advanced nonsquamous EGFR wild-type non-small-cell lung cancer segregated according to KRAS mutation status.
abstract: BACKGROUND
  We hypothesized that KRAS mutations function as a marker of poor sensitivity to first-line platinum-based chemotherapy in patients with advanced nonsquamous EGFR wild-type (WT) non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Consecutive advanced nonsquamous EGFR WT NSCLCs treated at the Medical Oncology of Perugia with simultaneous assessment of KRAS mutation status were eligible. Anaplastic lymphoma kinase (ALK) gene status was known in roughly half of the patients who had KRAS WT.
  
  
  RESULTS
  Two hundred four patients were included. Among them, the 77 individuals carrying a KRAS-mutant phenotype experienced a significantly inferior outcome in terms of response rate (P = .04), disease control rate (P = .05), and progression-free survival (PFS) (P = .05) compared with the EGFR WT/KRAS WT population. The association between KRAS mutation and shorter PFS remained statistically significant at multivariate analysis (hazard ratio [HR], 1.45). In addition, patients with KRAS mutations reported a significantly shorter overall survival (OS) compared with patients with EGFR WT/KRAS WT/ALK negativity (n = 64) (P = .02). Among patients with KRAS mutations, those harboring a mutation at codon 13 (n = 12) performed worse than those with a mutation at codon 12 (n = 62) in terms of both PFS and OS (P = .09 for both).
  
  
  CONCLUSIONS
  KRAS mutation appears to negatively affect sensitivity to first-line platinum-based chemotherapy in patients with advanced nonsquamous EGFR WT NSCLC. Studies on larger case series are needed to address differences in clinical outcome according to the type of mutation.
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy. Electronic address: giulio.metro@yahoo.com.
authors.forename: Giulio
authors.initials: G
authors.lastname: Metro
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Chiari
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bennati
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Cenci
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
authors.forename: Biagio
authors.initials: B
authors.lastname: Ricciuti
authors.affiliation: Department of Thoracic Surgery, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Puma
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Flacco
authors.affiliation: Department of Diagnostic Imaging, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rebonato
authors.affiliation: Biostatistics and Data Management Core, Regina Elena Cancer Institute, Rome, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
authors.forename: Vienna
authors.initials: V
authors.lastname: Ludovini
authors.affiliation: Department of Pathology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Bellezza
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Ferolla
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Minotti
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Crinò
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D015331:Cohort Studies; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D010984:Platinum / Q000008:administration & dosage; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D010984:Platinum; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: ALK; EGFR; KRAS; Non–small-cell lung cancer; Platinum-based chemotherapy