Update of IGF-1 receptor inhibitor (ganitumab, dalotuzumab, cixutumumab, teprotumumab and figitumumab) effects on cancer therapy.
Update of IGF-1 receptor inhibitor (ganitumab, dalotuzumab, cixutumumab, teprotumumab and figitumumab) effects on cancer therapy.
复制标题
DOI：
10.18632/oncotarget.15704
复制
发表时间：
2017-04-25
期刊：
影响因子：
--
通讯作者：
Du J
中科院分区：
文献类型：
--
作者：
Qu X;Wu Z;Dong W;Zhang T;Wang L;Pang Z;Ma W;Du J
胰岛素样生长因子-1受体（IGF-1R）抑制剂在癌症治疗中的预后研究取得了令人鼓舞的结果，这表明IGF-1R信号传导在癌细胞生长中至关重要。然而，后来的临床试验的结论显示，IGF-1R抑制剂治疗癌症的前景黯淡。我们进行这项分析是为了弄清楚IGF-1R抑制剂在临床癌症治疗中的作用。我们检索了关于IGF-1R抑制剂单药或与其他实体肿瘤治疗联合的最新研究。涉及5种IGF-1R抗药。主要终点为无进展生存期（PFS）。次要终点是总生存期（OS）。纳入了17项研究。总生存率（I2=37.1%， P=0.080， HR=1.08, 95% CI=0.97-1.21）和无进展生存率（I2=0.0%， P=0.637， HR=1.05, 95% CI=0.98-1.12）均无统计学意义。达妥珠单抗的OS、乳腺癌、结直肠癌和前列腺癌的PFS甚至显示出有害的影响。到目前为止，抗igf - 1r单抗体对实体瘤的预后没有显著影响。相反，在dalotuzumab、乳腺癌、结直肠癌和前列腺癌亚组中显示出悲观的效果。IGF-1R抗药物的进一步研究是必要的，但没有根据预测性生物标志物在未选择的患者中进行。
Prognostic studies of insulin-like growth factor-1 receptor(IGF-1R) inhibitors in cancer therapy had promising results in infratests, which exhibited that IGF-1R signalling was crucial in cancer cells growth. However, the conclusion of later clinical trials revealed a dim future for IGF-1R inhibitors to treat cancer. We conducted this analysis to figure out how IGF-1R inhibitors acted in clinical cancer therapy. We searched up-to-date studies about the single agent of IGF-1R inhibitors or combination with other therapies in solid tumor. Five IGF-1R anti-agents were involved. The primary endpoint was progression-free survival (PFS). The secondary endpoint was overall survival (OS). 17studies were enrolled. The results was not significant in overall survival (I2=37.1%, P=0.080, HR=1.08, 95% CI=0.97-1.21) and in progression-free survival (I2=0.0%, P=0.637, HR=1.05, 95% CI=0.98-1.12). OS for dalotuzumab, breast cancer, colorectal cancer, and PFS for prostate cancer even indicated harmful effects. So far, anti-IGF-1R mono-antibodies did not make significant differences in solid tumor prognosis. On the contrary, pessimistic effects were shown in the dalotuzumab, breast cancer, colorectal cancer and prostate cancer subgroups. Further studies of IGF-1R anti-agents were needed, but unwarranted in unselected patients by predictive biomarkers.