The Department of Clinical Development and Medical Affairs, Pfizer Oncology, New London, CT 06320, USA.
Br J Cancer. 2011 Jan 4;104(1):68-74. doi: 10.1038/sj.bjc.6605972. Epub 2010 Nov 23.
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.
抗胰岛素样生长因子-1 受体（IGF-1R）抗体 figitumumab（F）的 III 期临床试验最近因无效而在未经选择的非小细胞肺癌（NSCLC）患者中停止。在这里，我们研究了游离 IGF-1（fIGF-1）作为 F 治疗临床获益的潜在预测生物标志物的作用。
在一项单独给予紫杉醇和卡铂（PC）或联合给予 F 10 或 20mg/kg（PCF10、PCF20）的 II 期研究中，检测了 110 名晚期 NSCLC 患者的治疗前循环 fIGF-1 水平。
Cox 比例风险模型相互作用在 0.5-0.9ng/ml(-1)范围内的 fIGF-1 标准为 2.5 到 3.5。高于每个标准的患者在 PCF20 相关的 PC 治疗中无进展生存期显著改善。fIGF-1 与 IGF 结合蛋白 1（IGFBP-1，ρ=-0.295，P=0.005）呈负相关，治疗前胰岛素与 IGFBP-1 的比值也可预测 F 的临床获益。此外，fIGF-1 水平与肿瘤波形蛋白表达呈正相关（ρ=0.594，P=0.021），与 E-钙粘蛋白呈负相关（ρ=-0.389，P=0.152），提示 fIGF-1 可能在肿瘤去分化中起作用。
游离 IGF-1 可能有助于确定从 F 治疗中获益的 NSCLC 患者亚组。
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