title: Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): a randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX.
abstract: Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression.
  
  
  
  We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progression-free survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis.
  
  
  
  Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 [95% confidence interval (CI) 4.7-8.0] versus 4.5 months (95% CI 3.3-5.7); [hazard ratio (HR), 0.81; 95% CI 0.58-1.12; P = 0.19], respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm [median 6.9 (95% CI 5.5-8.2) versus 5.3 months (95% CI 3.7-6.9); HR, 0.56 (95% CI 0.33-0.94); P = 0.025]. There was a trend in better overall survival: median 23.7 [(95% CI 19.4-28.0) versus 19.8 months (95% CI 14.9-24.7); HR, 0.57 (95% CI 0.32-1.02); P = 0.056].
  
  
  
  Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials.
authors.affiliation: Medical Oncology, Department of Clinical and Experimental Medicine 'F. Magrassi', Second University of Naples, Naples. Electronic address: fortunato.ciardiello@unina2.it.
authors.forename: F
authors.initials: F
authors.lastname: Ciardiello
authors.affiliation: Cell Biology and Biotherapy Unit, National Cancer Institute 'Fondazione Giovanni Pascale', Naples.
authors.forename: N
authors.initials: N
authors.lastname: Normanno
authors.affiliation: Medical Oncology, Department of Clinical and Experimental Medicine 'F. Magrassi', Second University of Naples, Naples.
authors.forename: E
authors.initials: E
authors.lastname: Martinelli
authors.affiliation: Medical Oncology, Department of Clinical and Experimental Medicine 'F. Magrassi', Second University of Naples, Naples.
authors.forename: T
authors.initials: T
authors.lastname: Troiani
authors.affiliation: Medical Oncology, Hospital SS. Annunziata, Taranto.
authors.forename: S
authors.initials: S
authors.lastname: Pisconti
authors.affiliation: Medical Oncology, Department of Clinical and Experimental Medicine 'F. Magrassi', Second University of Naples, Naples.
authors.forename: C
authors.initials: C
authors.lastname: Cardone
authors.affiliation: Medical Oncology, Department of Clinical and Experimental Medicine 'F. Magrassi', Second University of Naples, Naples.
authors.forename: A
authors.initials: A
authors.lastname: Nappi
authors.affiliation: Medical Oncology, Hospital Garibaldi, Nesima, Catania.
authors.forename: A R
authors.initials: AR
authors.lastname: Bordonaro
authors.affiliation: Cell Biology and Biotherapy Unit, National Cancer Institute 'Fondazione Giovanni Pascale', Naples; Laboratory of Pharmacogenomics, Centro di Ricerche Oncologiche di Mercogliano (CROM)-National Cancer Institute 'Fondazione Giovanni Pascale', Naples.
authors.forename: M
authors.initials: M
authors.lastname: Rachiglio
authors.affiliation: Cell Biology and Biotherapy Unit, National Cancer Institute 'Fondazione Giovanni Pascale', Naples; Laboratory of Pharmacogenomics, Centro di Ricerche Oncologiche di Mercogliano (CROM)-National Cancer Institute 'Fondazione Giovanni Pascale', Naples.
authors.forename: M
authors.initials: M
authors.lastname: Lambiase
authors.affiliation: Medical Oncology, Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo (Foggia).
authors.forename: T P
authors.initials: TP
authors.lastname: Latiano
authors.affiliation: Medical Oncology, Hospital SS. Annunziata, Taranto.
authors.forename: G
authors.initials: G
authors.lastname: Modoni
authors.affiliation: Medical Oncology, Hospital Garibaldi, Nesima, Catania.
authors.forename: S
authors.initials: S
authors.lastname: Cordio
authors.affiliation: Medical Oncology, National Cancer Institute Giovanni Paolo II, Bari.
authors.forename: F
authors.initials: F
authors.lastname: Giuliani
authors.affiliation: Medical Oncology, Hospital 'A. Cardarelli', Naples.
authors.forename: M
authors.initials: M
authors.lastname: Biglietto
authors.affiliation: Medical Oncology, Hospital Monaldi- Azienda Ospedaliera dei Colli, Naples.
authors.forename: V
authors.initials: V
authors.lastname: Montesarchio
authors.affiliation: Medical Oncology, University Hospital A. Gemelli, Rome.
authors.forename: C
authors.initials: C
authors.lastname: Barone
authors.affiliation: Policlinico Universitario Campus Bio-Medico, Rome.
authors.forename: G
authors.initials: G
authors.lastname: Tonini
authors.affiliation: Medical Oncology, Hospital A. Perrino, Brindisi.
authors.forename: S
authors.initials: S
authors.lastname: Cinieri
authors.affiliation: Medical Oncology, Hospital Sacro Cuore di Gesù, Fatebenefratelli, Benevento.
authors.forename: A
authors.initials: A
authors.lastname: Febbraro
authors.affiliation: GOIM Trial Office, Bari, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Rizzi
authors.affiliation: Medical Oncology, Department of Clinical and Experimental Medicine 'F. Magrassi', Second University of Naples, Naples.
authors.forename: F
authors.initials: F
authors.lastname: De Vita
authors.affiliation: Medical Oncology, Department of Clinical and Experimental Medicine 'F. Magrassi', Second University of Naples, Naples.
authors.forename: M
authors.initials: M
authors.lastname: Orditura
authors.affiliation: Medical Oncology, National Cancer Institute Giovanni Paolo II, Bari.
authors.forename: G
authors.initials: G
authors.lastname: Colucci
authors.affiliation: Medical Oncology, Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo (Foggia).
authors.forename: E
authors.initials: E
authors.lastname: Maiello
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068818:Cetuximab / Q000008:administration & dosage* / Q000009:adverse effects; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007558:Italy; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016896:Treatment Outcome
chemical_list: C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil
keywords: FOLFOX; NGS; cetuximab; colorectal cancer