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nature portfolio privacy policy research nature middle line represents advertising thermo scientific body mass index social media author information authors 0/ reprints italy assessing her2/neu amplification assessing k-ras mutations drug development full size image author correspondence eml4-alk gene fusion eml4-alk fusion gene open-label open label rabbit anti-pan-cytokeratin small-cell lung cancer pre-treatment circulating levels receiver-operating characteristic total alanine-scanning mutagenesis growth factor-binding proteins kaplan–meier curves plasma concentration–time curve low e-cadherin expression anti-igf-ir therapy high pre-treatment levels f-ihc aqua scores pre-treatment biomarker tests pre-treatment figf-1 levels binding protein-3-selective insulin chemotherapy-naïve stage iiib mouse anti-e-cadherin long-term clinical benefit tumour e-cadherin/vimentin ratio patients received pc significant biomarker/treatment interaction pre-treatment figf-1 criteria permissions small sample size egf receptor family progression-free survival clinical development dolled-filhart mp higher baseline levels

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