Pre-treatment levels of circulating free IGF-1 identify NSCLC patients who derive clinical benefit from figitumumab
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Post-publication record
- Nature
- Retraction
- Reason
- Unreliable Results and/or Conclusions;
- Date
- 12/4/2012 0:00
- Flagged by OpenAlex?
- Yes
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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.
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The record
- Venue
- British Journal of Cancer
- Topic
- Growth Hormone and Insulin-like Growth Factors
- Field
- Medicine
- Canadian institutions
- McGill University
- Funders
- National Institute of Environmental Health SciencesNational Institutes of HealthPfizer
- Keywords
- MedicineInternal medicineBiomarkerOncologyLung cancerProportional hazards modelCarboplatinProgression-free survivalClinical trialnon-small cell lung cancer (NSCLC)ChemotherapyBiologyCisplatin
- Has abstract in OpenAlex
- yes