title: Phase II study of necitumumab plus modified FOLFOX6 as first-line treatment in patients with locally advanced or metastatic colorectal cancer.
abstract: BACKGROUND
  This single-arm phase II study investigated the EGFR monoclonal antibody necitumumab plus modified FOLFOX6 (mFOLFOX6) in first-line treatment of locally advanced or metastatic colorectal cancer (mCRC).
  
  
  METHODS
  Patients received 800-mg intravenous necitumumab (day 1; 2-week cycles), followed by oxaliplatin 85 mg m(-2), folinic acid 400 mg m(-2), and 5-fluorouracil (400 mg m(-2) bolus then 2400 mg m(-2) over 46 h). Radiographic evaluation was performed every 8 weeks until progression. Primary endpoint was objective response rate.
  
  
  RESULTS
  Forty-four patients were enrolled and treated. Objective response rate was 63.6% (95% confidence interval 47.8-77.6); complete response was observed in four patients; median duration of response was 10.0 months (7.0-16.0). Median overall survival (OS) and progression-free survival (PFS) were 22.5 (11.0-30.0) and 10.0 months (7.0-12.0), respectively. Clinical outcome was better in patients with KRAS exon 2 wild type (median OS 30.0 months (23.0-NA); median PFS 12.0 (8.0-20.0)), compared with KRAS exon 2 mutant tumours (median OS 7.0 months (5.0-37.0); median PFS 7.0 (4.0-18.0)). The most common grade ⩾3 adverse events were neutropenia (29.5%), asthenia (27.3%), and rash (20.5%).
  
  
  CONCLUSIONS
  First-line necitumumab+mFOLFOX6 was active with manageable toxicity in locally advanced or mCRC; additional evaluation of the impact of tumour RAS mutation status is warranted.
authors.affiliation: Vall d'Hebron Institute of Oncology Barcelona, Spain and Universitat Autònoma de Barcelona, 08035 Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Elez
authors.affiliation: Institut Jules Bordet, 1000 Brussels, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Hendlisz
authors.affiliation: Centres Hospitaliers Jolimont, 7100 Haine Saint-Paul, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Delaunoit
authors.affiliation: Hospital Universitario San Carlos, 28040 Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Sastre
authors.affiliation: Biomedical Research Institute INCLIVA, University of Valencia, 46010 Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Cervantes
authors.affiliation: Eli Lilly and Company, 28108 Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Varea
authors.affiliation: Eli Lilly and Company, 08807 Bridgewater, NJ, USA.
authors.forename: G
authors.initials: G
authors.lastname: Chao
authors.affiliation: Eli Lilly and Company, 16973 Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Wallin
authors.affiliation: Vall d'Hebron Institute of Oncology Barcelona, Spain and Universitat Autònoma de Barcelona, 08035 Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Tabernero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C527969:necitumumab; D016283:Proto-Oncogene Proteins p21(ras); D002955:Leucovorin; D005472:Fluorouracil