Pre-treatment levels of circulating free IGF-1 identify NSCLC patients who derive clinical benefit from figitumumab

Br J Cancer. 2011 Jan 4;104(1):68-74. doi: 10.1038/sj.bjc.6605972. Epub 2010 Nov 23.

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.

Materials and method: 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.

Conclusion: Free IGF-1 may contribute to the identification of a subset of NSCLC patients who benefit from F therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood
  • Cadherins / blood
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Clinical Trials, Phase II as Topic
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulins, Intravenous
  • Insulin / blood
  • Insulin-Like Growth Factor Binding Protein 1 / blood
  • Insulin-Like Growth Factor I / metabolism*
  • Lung Neoplasms / blood*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Neoplasm Staging
  • Paclitaxel / administration & dosage
  • Randomized Controlled Trials as Topic
  • Survival Rate
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • Cadherins
  • Immunoglobulins, Intravenous
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor I
  • Carboplatin
  • Paclitaxel
  • figitumumab