title: Pre-treatment levels of circulating free IGF-1 identify NSCLC patients who derive clinical benefit from figitumumab.
abstract: BACKGROUND
  Phase III trials of the anti-insulin-like growth factor type 1 receptor (IGF-IR) antibody figitumumab (F) in unselected non-small-cell lung cancer (NSCLC) patients were recently discontinued owing to futility. Here, we investigated a role of free IGF-1 (fIGF-1) as a potential predictive biomarker of clinical benefit from F treatment.
  
  
  METHODS
  Pre-treatment circulating levels of fIGF-1 were tested in 110 advanced NSCLC patients enrolled in a phase II study of paclitaxel and carboplatin given alone (PC) or in combination with F at doses of 10 or 20 mg kg(-1) (PCF10, PCF20).
  
  
  RESULTS
  Cox proportional hazards model interactions were between 2.5 and 3.5 for fIGF-1 criteria in the 0.5-0.9 ng ml(-1) range. Patients above each criterion had a substantial improvement in progression-free survival on PCF20 related to PC alone. Free IGF-1 correlated inversely with IGF binding protein 1 (IGFBP-1, ρ=-0.295, P=0.005), and the pre-treatment ratio of insulin to IGFBP-1 was also predictive of F clinical benefit. In addition, fIGF-1 levels correlated with tumour vimentin expression (ρ=0.594, P=0.021) and inversely with E-cadherin (ρ=-0.389, P=0.152), suggesting a role for fIGF-1 in tumour de-differentiation.
  
  
  CONCLUSIONS
  Free IGF-1 may contribute to the identification of a subset of NSCLC patients who benefit from F therapy.
authors.affiliation: The Department of Clinical Development and Medical Affairs, Pfizer Oncology, New London, CT 06320, USA. antonio.gualberto@mpi.com
authors.forename: A
authors.initials: A
authors.lastname: Gualberto
authors.forename: M L
authors.initials: ML
authors.lastname: Hixon
authors.forename: D D
authors.initials: DD
authors.lastname: Karp
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Green
authors.forename: M
authors.initials: M
authors.lastname: Dolled-Filhart
authors.forename: L G
authors.initials: LG
authors.lastname: Paz-Ares
authors.forename: S
authors.initials: S
authors.lastname: Novello
authors.forename: J
authors.initials: J
authors.lastname: Blakely
authors.forename: C J
authors.initials: CJ
authors.lastname: Langer
authors.forename: M N
authors.initials: MN
authors.lastname: Pollak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D015820:Cadherins / Q000097:blood; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016756:Immunoglobulins, Intravenous; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D015820:Cadherins; D016756:Immunoglobulins, Intravenous; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D016190:Carboplatin; D017239:Paclitaxel; C525021:figitumumab