title: Prospective study of a molecular selection profile for RAS wild type colorectal cancer patients receiving irinotecan-cetuximab.
abstract: BACKGROUND
  The aim of our study was to evaluate whether a panel of biomarkers, prospectively analysed might be able to predict patients' clinical outcome more accurately than RAS status alone.
  
  
  METHODS
  K-RAS (exons 2, 3, 4) wild type colorectal cancer patients, candidates to second/third-line cetuximab with chemotherapy were prospectively allocated into 2 groups on the basis of their profile: favourable (BRAF and PIK3CA exon 20 wild type, EGFR GCN ≥ 2.6, HER-3 Rajkumar score ≤ 8, IGF-1 immunostaining < 2) or unfavourable (any of the previous markers altered or mutated). After the introduction of N-RAS status (exons 2, 3, 4) only RAS wild type patients were considered eligible. Primary aim was response rate (RR). To detect a difference in terms of RR among patients with an unfavourable profile (estimated around 25%) and patients with a favourable profile (estimated around 60%), with a probability alpha of 0.05 and beta of 0.05, required sample size was 46 patients. Secondary endpoints were progression free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  Forty-six patients were enrolled. Seventeen patients (37%) were allocated to the favourable and 29 patients (63%) to the unfavourable profile. RR in the favourable and unfavourable group was 11/17 (65%) and 2/29 (7%) (p = 0.007) respectively. The favourable group also showed an improved PFS (8 months vs. 3 months, p < 0.0001) and OS (15 months vs. 6 months, p < 0.0001).
  
  
  CONCLUSIONS
  Our results suggest that prospective selection of optimal candidates for cetuximab treatment is feasible and may be able to improve clinical outcome.
authors.affiliation: Department of Medical Oncology, University Hospital of Ancona, Polytechnic University of the Marche, Ancona, Italy. riccardo.giampieri81@gmail.com.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giampieri
authors.affiliation: Department of Pathology, University Hospital of Ancona, Polytechnic University of the Marche, Ancona, Italy. a.mandolesi@univpm.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mandolesi
authors.affiliation: Department of Medical Oncology, International Medical Center of Jeddah, Jeddah, KSA. KAbouelkhair@imc.med.sa.
authors.forename: Khaled M
authors.initials: KM
authors.lastname: Abouelkhair
authors.affiliation: Department of Medical Oncology, University Hospital of Ancona, Polytechnic University of the Marche, Ancona, Italy. c.loretelli@univpm.it.
authors.forename: Cristian
authors.initials: C
authors.lastname: Loretelli
authors.affiliation: Department of Medical Oncology, University Hospital of Ancona, Polytechnic University of the Marche, Ancona, Italy. micheladelprete@gmail.com.
authors.forename: Michela
authors.initials: M
authors.lastname: Del Prete
authors.affiliation: Department of Medical Oncology, University Hospital of Ancona, Polytechnic University of the Marche, Ancona, Italy. lucafaloppi@gmail.com.
authors.forename: Luca
authors.initials: L
authors.lastname: Faloppi
authors.affiliation: Department of Medical Oncology, University Hospital of Ancona, Polytechnic University of the Marche, Ancona, Italy. stellabia@virgilio.it.
authors.forename: Bianconi
authors.initials: B
authors.lastname: Maristella
authors.affiliation: Department of Medical Oncology, International Medical Center of Jeddah, Jeddah, KSA. Eibrahim@imc.med.sa.
authors.forename: Ezzeldin M
authors.initials: EM
authors.lastname: Ibrahim
authors.affiliation: Department of Pathology, University Hospital of Ancona, Polytechnic University of the Marche, Ancona, Italy. m.scarpelli@univpm.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Scarpelli
authors.affiliation: Department of Medical Oncology, University Hospital of Ancona, Polytechnic University of the Marche, Ancona, Italy. cascinu@yahoo.com.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: Department of Medical Oncology, Medical Oncology, University Hospital of Cagliari, University of Cagliari, Cagliari, Italy. marioscartozzi@gmail.com.
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068818:Cetuximab / Q000008:administration & dosage*; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism; D005091:Exons; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D000077146:Irinotecan; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011446:Prospective Studies; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D008565:Membrane Proteins; D007334:Insulin-Like Growth Factor I; D000077146:Irinotecan; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C581292:ERBB3 protein, human; D066246:ErbB Receptors; D020893:Receptor, ErbB-3; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab; D002166:Camptothecin