title: Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  As suggested by in-vitro data, we hypothesize that subtypes of KRAS mutated non-small cell lung cancer (NSCLC) respond differently to chemotherapy regimens.
  
  
  METHODS
  Patients with advanced NSCLC and known KRAS mutation, treated with first-line platinum-based chemotherapy, were retrieved from hospital databases.
  
  
  OBJECTIVE
  to investigate overall response rate (ORR), progression free survival (PFS) and overall survival (OS) between different types of platinum-based chemotherapy per type of KRAS mutation.
  
  
  RESULTS
  464 patients from 17 hospitals, treated between 2000 and 2013, were included. The majority of patients had stage IV disease (93%), had a history of smoking (98%) and known with an adenocarcinoma (91%). Most common types of KRAS mutation were G12C (46%), G12V (20%) and G12D (10%). Platinum was combined with pemetrexed (n=334), taxanes (n=68) or gemcitabine (n=62). Patients treated with taxanes had a significant improved ORR (50%) compared to pemetrexed (21%) or gemcitabine (25%; p<0.01). Patients treated with bevacizumab in addition to taxanes (n=38) had the highest ORR (62%). The PFS was significantly improved in patients treated with taxanes compared to pemetrexed (HR=0.72, p=0.02), but not OS (HR=0.87, p=0.41). In patients with G12V, significantly improved ORR (p<0.01) was observed for taxanes, but not PFS or OS. Patients with G12C or G12D mutation had comparable ORR, PFS and OS in all treatment groups.
  
  
  CONCLUSIONS
  KRAS mutated NSCLC patients treated with taxane-based chemotherapy had best ORR. Response to chemotherapy regimens was different in types of KRAS mutation. Especially patients with G12V had better response to taxane treatment.
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Wouter W
authors.initials: WW
authors.lastname: Mellema
authors.affiliation: Department of Pulmonary Diseases, Jeroen Bosch hospital's-Hertogenbosch, Netherlands.
authors.forename: Lucie
authors.initials: L
authors.lastname: Masen-Poos
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, Netherlands. Electronic address: ef.smit@vumc.nl.
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.affiliation: Department of Pulmonary Diseases, Maastricht University Medical Center, Maastricht, Netherlands.
authors.forename: Lizza E L
authors.initials: LE
authors.lastname: Hendriks
authors.affiliation: Department of Pulmonary Diseases, Amphia hospital, Breda, Netherlands.
authors.forename: Joachim G
authors.initials: JG
authors.lastname: Aerts
authors.affiliation: Department of Pulmonary Diseases, Canisius Wilhemina hospital, Nijmegen, Netherlands.
authors.forename: Arien
authors.initials: A
authors.lastname: Termeer
authors.affiliation: Department of Pulmonary Diseases, Gelre hospital, Zutphen, Netherlands.
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: Goosens
authors.affiliation: Department of Pulmonary Diseases, Rijnstate hospital, Arnhem, Netherlands.
authors.forename: Hans J M
authors.initials: HJ
authors.lastname: Smit
authors.affiliation: Department of Thoracic Oncology, NKI-AvL, Amsterdam, Netherlands.
authors.forename: Michel M
authors.initials: MM
authors.lastname: van den Heuvel
authors.affiliation: Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Anthonie J
authors.initials: AJ
authors.lastname: van der Wekken
authors.affiliation: Department of Pulmonary Diseases, St Antonius hospital, Nieuwegein, Netherlands.
authors.forename: Gerarda J M
authors.initials: GJ
authors.lastname: Herder
authors.affiliation: Department of Pulmonary Diseases, Spaarne hospital, Hoofddorp, Netherlands.
authors.forename: Frans H
authors.initials: FH
authors.lastname: Krouwels
authors.affiliation: Department of Pulmonary Diseases, Isala clinics, Zwolle, Netherlands.
authors.forename: Jos A
authors.initials: JA
authors.lastname: Stigt
authors.affiliation: Department of Pulmonary Diseases, Catharina hospital, Eindhoven, Netherlands.
authors.forename: Ben E E M
authors.initials: BE
authors.lastname: van den Borne
authors.affiliation: Department of Pulmonary Diseases, Alkmaar Medical Center, Alkmaar, Netherlands.
authors.forename: Tjeerd J
authors.initials: TJ
authors.lastname: Haitjema
authors.affiliation: Department of Pulmonary Diseases, Ziekenhuis groep Twente, Almelo, Netherlands.
authors.forename: Agnes J
authors.initials: AJ
authors.lastname: Staal-Van den Brekel
authors.affiliation: Department of Pulmonary Diseases, Deventer hospital, Deventer, Netherlands.
authors.forename: Robbert C
authors.initials: RC
authors.lastname: van Heemst
authors.affiliation: Department of Pulmonary Diseases, Groene Hart hospital, Gouda, Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Pouw
authors.affiliation: Department of Pulmonary Diseases, Maastricht University Medical Center, Maastricht, Netherlands.
authors.forename: Anne-Marie C
authors.initials: AM
authors.lastname: Dingemans
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006147:Guanine / Q000008:administration & dosage; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011379:Prognosis; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D018631:ras Proteins / Q000235:genetics*; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D043823:Taxoids; D003841:Deoxycytidine; D006147:Guanine; D018631:ras Proteins; D000093542:Gemcitabine
keywords: Chemotherapy; KRAS mutation; Non-small cell lung cancer; Outcome; Type of KRAS mutation