title: Contrasted outcomes to gefitinib on tumoral IGF1R expression in head and neck cancer patients receiving postoperative chemoradiation (GORTEC trial 2004-02).
abstract: OBJECTIVE
  Intermediate/high-risk operated patients with head and neck cancer may benefit from the addition of EGF receptor (EGFR) inhibitor gefitinib to chemoradiation. This study was designed to assess improved outcomes and identify predictive biomarkers.
  
  
  METHODS
  Patients provided informed consent for tumor biomarker analyses and, when eligible, were further enrolled in the therapeutic CARISSA multicenter randomized phase II trial of postoperative irradiation with cisplatin + gefitinib (GORTEC 2004-02-NCT00169221).
  
  
  RESULTS
  Seventy-nine patients were included in the biomarker study, whereas 27 did not meet prerequisites for randomization between gefitinib and placebo. Two-year disease-free survival (DFS) rate was 65.0% and did not differ between randomized patients treated with gefitinib or placebo (P = 0.85). The similarity of DFS curves between nonrandomized patients (n = 27), randomized patients without gefitinib (n = 27), and randomized patients receiving gefitinib (n = 25), and similar histoclinical parameter distributions for all groups, allowed us to conduct statistical analyses on the entire population. On multivariate analysis, elevated expression of PAK1 by Western blotting, CD31 and membranous insulin-like growth factor 1 receptor (IGF1R) both by immunohistochemistry was significantly associated with shorter DFS. There was a significant interaction between IGF1R and gefitinib. Gefitinib abolished the prognostic discriminative power of high IGF1R expression; patients with elevated IGF1R expression benefited from gefitinib whereas those with low IGF1R fared worse.
  
  
  CONCLUSIONS
  Gefitinib treatment affords no significant clinical benefit on DFS in an unselected population of patients with head and neck cancer. Our results point to the potential advantage of personalizing treatment for gefitinib based on tumoral IGF1R expression. This should foster confirmatory analyses in trials involving EGFR-targeting agents.
authors.affiliation: University of Nice-Sophia Antipolis, Department of Pathology, Centre Antoine Lacassagne - Institut Universitaire de la Face et du Cou (IUFC), Centre Antoine Lacassagne, Nice, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Thariat
authors.forename: René-Jean
authors.initials: RJ
authors.lastname: Bensadoun
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Etienne-Grimaldi
authors.forename: Dominique
authors.initials: D
authors.lastname: Grall
authors.forename: Frédérique
authors.initials: F
authors.lastname: Penault-Llorca
authors.forename: Olivier
authors.initials: O
authors.lastname: Dassonville
authors.forename: Francois
authors.initials: F
authors.lastname: Bertucci
authors.forename: Anne
authors.initials: A
authors.lastname: Cayre
authors.forename: Dominique
authors.initials: D
authors.lastname: De Raucourt
authors.forename: Lionnel
authors.initials: L
authors.lastname: Geoffrois
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.forename: Philippe
authors.initials: P
authors.lastname: Giraud
authors.forename: Séverine
authors.initials: S
authors.lastname: Racadot
authors.forename: Sylvain
authors.initials: S
authors.lastname: Morinière
authors.forename: Anne
authors.initials: A
authors.lastname: Sudaka
authors.forename: Ellen
authors.initials: E
authors.lastname: Van Obberghen-Schilling
authors.forename: Gérard
authors.initials: G
authors.lastname: Milano
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011184:Postoperative Period; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D017526:Receptor, IGF Type 1; D000077156:Gefitinib