title: Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer.
abstract: BACKGROUND
  Selumetinib (AZD6244, ARRY-142886)+docetaxel increases median overall survival (OS) and significantly improves progression-free survival (PFS) and objective response rate (ORR) compared with docetaxel alone in patients with KRAS mutant, stage IIIB/IV non-small-cell lung cancer (NSCLC; NCT00890825).
  
  
  METHODS
  Retrospective analysis of OS, PFS, ORR and change in tumour size at week 6 for different sub-populations of KRAS codon mutations.
  
  
  RESULTS
  In patients receiving selumetinib+docetaxel and harbouring KRAS G12C or G12V mutations there were trends towards greater improvement in OS, PFS and ORR compared with other KRAS mutations.
  
  
  CONCLUSIONS
  Different KRAS mutations in NSCLC may influence selumetinib/docetaxel sensitivity.
authors.affiliation: Lowe Center for Thoracic Oncology and the Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Jänne
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield SK10 4TF, UK.
authors.forename: I
authors.initials: I
authors.lastname: Smith
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield SK10 4TF, UK.
authors.forename: G
authors.initials: G
authors.lastname: McWalter
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield SK10 4TF, UK.
authors.forename: H
authors.initials: H
authors.lastname: Mann
authors.affiliation: AstraZeneca, Gatehouse Park, Waltham, MA 02451, USA.
authors.forename: B
authors.initials: B
authors.lastname: Dougherty
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield SK10 4TF, UK.
authors.forename: J
authors.initials: J
authors.lastname: Walker
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield SK10 4TF, UK.
authors.forename: M C M
authors.initials: MC
authors.lastname: Orr
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield SK10 4TF, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Hodgson
authors.affiliation: Department of Medicine, Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, MA 02114, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Shaw
authors.affiliation: Instituto Brasileiro de Cancerologia Torácica, Rua Dr. Martinico Prado, 26/101, Higienópolis, Sao Paulo 01224-010, Brazil.
authors.forename: J R
authors.initials: JR
authors.lastname: Pereira
authors.affiliation: Department of Pneumology, Hôpital Gabriel Montpied, 58 Rue Montalembert, 63000 Clermont-Ferrand, France.
authors.forename: G
authors.initials: G
authors.lastname: Jeannin
authors.affiliation: Department of Pneumology, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Vansteenkiste
authors.affiliation: Department of Medicine, PUCRS School of Medicine, Padre Chagas 66, 203, Porto Alegre RS 90 570 080, Brazil.
authors.forename: C H
authors.initials: CH
authors.lastname: Barrios
authors.affiliation: CACON, Hospital de Caridade de Ijuí, Avenida David José Martins, 152-Centro, Ijuí RS 98700-000, Brazil.
authors.forename: F A
authors.initials: FA
authors.lastname: Franke
authors.affiliation: Department of Oncology, University Medical School Perugia, Piazza Università 1, 06123 Perugia, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Crinò
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield SK10 4TF, UK.
authors.forename: P
authors.initials: P
authors.lastname: Smith
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D003062:Codon; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D018631:ras Proteins / Q000235:genetics*
chemical_list: C517975:AZD 6244; D001562:Benzimidazoles; D003062:Codon; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D043823:Taxoids; D000077143:Docetaxel; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins