title: Panitumumab combined with irinotecan for patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy: a GERCOR efficacy, tolerance, and translational molecular study.
abstract: BACKGROUND
  The purpose of this study was to evaluate the combination of panitumumab and irinotecan in patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy (oxaliplatin, fluoropyrimidines-irinotecan and bevacizumab).
  
  
  METHODS
  KRAS status was first determined locally but subsequent validation of KRAS status and additional screenings (rare KRAS, NRAS, BRAF mutations and EGFR copy number) were centrally assessed. Patients received panitumumab (6 mg/kg) and irinotecan (180 mg/m²) every 2 weeks.
  
  
  RESULTS
  Sixty-five eligible patients were analyzed. The objective response rate (ORR) was 29.2% [95% confidence interval (95% CI) 18.2-40.3]. Median progression-free and overall survivals were 5.5 and 9.7 months, respectively. Most frequent grade 3/4 toxic effects were skin 32.3%, diarrhea 15.4% and neutropenia 12.3%. Tissue samples were available for 60 patients. For the confirmed KRAS wild-type population codon 12 or 13 mutation (n = 54), ORR was 35.2% (95% CI 22.4.1-47.9). Thirteen patients had a NRAS, a BRAF or a rare KRAS mutation, and no tumor response was observed in this subgroup when compared with 46.3% (95% CI 31.1-61.6) ORR in the subgroup of 41 patients with no identified mutation.
  
  
  CONCLUSIONS
  Panitumumab and irinotecan is an active third-line regimen in a well-defined population based on biomarkers. ClinicalTrials.gov Identifier NCT00655499.
authors.affiliation: Department of medical Oncology, Hôpital Saint-Antoine, Université Paris VI, Paris; Department of Clinical Research, GERCOR, Paris. Electronic address: thierry.andre@sat.aphp.fr.
authors.forename: T
authors.initials: T
authors.lastname: André
authors.affiliation: Université Paris Sorbonne Cité; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) - S775 Molecular Basis of Xenobiotics Response; Assistance Publique Hôpitaux de Paris Hôpital Européen Georges Pompidou, Paris.
authors.forename: H
authors.initials: H
authors.lastname: Blons
authors.affiliation: Department of Clinical Research, GERCOR, Paris; Department of medical Oncology,Hôpital Foch, Suresnes, France.
authors.forename: M
authors.initials: M
authors.lastname: Mabro
authors.affiliation: Department of medical Oncology, Hôpital Saint-Antoine, Université Paris VI, Paris; Department of Clinical Research, GERCOR, Paris.
authors.forename: B
authors.initials: B
authors.lastname: Chibaudel
authors.affiliation: Department of Clinical Research, GERCOR, Paris; Department of Hepato-Gastro-Enterology, Hôpital La Pitié Salpetrière, Paris.
authors.forename: J-B
authors.initials: JB
authors.lastname: Bachet
authors.affiliation: Department of medical Oncology, Hôpital Saint-Antoine, Université Paris VI, Paris; Department of Clinical Research, GERCOR, Paris.
authors.forename: C
authors.initials: C
authors.lastname: Tournigand
authors.affiliation: Department of Clinical Research, GERCOR, Paris; Department of medical Oncology, Institut Mutualiste Montsouris, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Bennamoun
authors.affiliation: Department of Clinical Research, GERCOR, Paris; Departement of Hepato-Gastro-Enterology, Hôpital Privé Jean Mermoz, Lyon, France.
authors.forename: P
authors.initials: P
authors.lastname: Artru
authors.affiliation: Department of medical Oncology, Centre Hospitalier de Beauvais, Beauvais, France.
authors.forename: S
authors.initials: S
authors.lastname: Nguyen
authors.affiliation: Department of medical Oncology, Hôpital Saint-Antoine, Université Paris VI, Paris.
authors.forename: C
authors.initials: C
authors.lastname: Ebenezer
authors.affiliation: Department of Clinical Research, GERCOR, Paris.
authors.forename: N
authors.initials: N
authors.lastname: Aissat
authors.affiliation: Biology and Tumor Pathology Department, Centre Jean-Perrin, Université d'Auvergne Equipe Associée EA4233 Centre Hospitalier Universitaire (CHU) Clermont-Ferrand.
authors.forename: A
authors.initials: A
authors.lastname: Cayre
authors.affiliation: Biology and Tumor Pathology Department, Centre Jean-Perrin, Université d'Auvergne Equipe Associée EA4233 Centre Hospitalier Universitaire (CHU) Clermont-Ferrand.
authors.forename: F
authors.initials: F
authors.lastname: Penault-Llorca
authors.affiliation: Université Paris Sorbonne Cité; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) - S775 Molecular Basis of Xenobiotics Response; Assistance Publique Hôpitaux de Paris Hôpital Européen Georges Pompidou, Paris.
authors.forename: P
authors.initials: P
authors.lastname: Laurent-Puig
authors.affiliation: Department of medical Oncology, Hôpital Saint-Antoine, Université Paris VI, Paris; Department of Clinical Research, GERCOR, Paris.
authors.forename: A
authors.initials: A
authors.lastname: de Gramont
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D000077544:Panitumumab; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D000077544:Panitumumab; D000077146:Irinotecan; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D002166:Camptothecin