title: Necitumumab in the treatment of advanced non-small cell lung cancer: translation from preclinical to clinical development.
abstract: BACKGROUND
  Treatment outcomes in unselected patients with advanced NSCLC remain disappointing with platinum-based chemotherapy. The addition of monoclonal antibodies targeting EGFR to standard first-line therapy is a validated strategy and has been associated with statistically significant survival advantage in advanced NSCLC. Necitumunab is a fully human IgG1 monoclonal antibody targeting EGFR, having the potential benefit of lower hypersensitivity reaction risk as compared with cetuximab and also equivalent antibody-dependent cell-mediated cytotoxicity.
  
  
  METHODS
  This paper reviews literature on preclinical and early clinical development of necitumumab that is available in PubMed and published abstracts from conferences, as well as ongoing trials as specified by clinicaltrials.gov. Recently, the Phase III clinical trial evaluating the addition of necitumumab to pemetrexed and cisplatin in non-squamous NSCLC was prematurely closed due to concerns about the increased risk of thromboembolic events in the experimental arm. Accrual in the Phase III trial of necitumumab in combination with gemcitabine and cisplatin in squamous NSCLC is ongoing.
  
  
  CONCLUSIONS
  Results of the ongoing large randomized trials will be instrumental in determining the drug's clinical significance and, with the analysis of potential molecular predictive factors, are expected to bring valuable additions to future therapeutic strategies in NSCLC.
authors.affiliation: Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Molecular Therapeutic Research Unit, Medical Oncology Service, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Dienstmann
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Felip
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000628:therapy*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C527969:necitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors