RETRACTED: Pre-treatment levels of circulating free IGF-1 identify NSCLC patients who derive clinical benefit from figitumumab (Retracted article. See vol. 107, pg. 2024, 2012)

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 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, rho = -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 (rho = 0.594, P = 0.021) and inversely with E-cadherin (rho = -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. British Journal of Cancer (2011) 104, 68-74. doi:10.1038/sj.bjc.6605972 www.bjcancer.com Published online 23 November 2010 (C) 2011 Cancer Research UK