贝伐珠单抗在晚期非鳞非小细胞肺癌治疗中的相关血浆生物标志物研究被引量：3

The study on plasma biomarkers of bevacizumab in the treatment of advanced non-small cell lung cancer

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摘要目的旨在探讨生物标志物和贝伐珠单抗治疗晚期非鳞非小细胞肺癌有效率的相关性。方法使用贝伐珠单抗联合化疗治疗的晚期非鳞非小细胞肺癌可入组该研究。根据研究者的决定,化疗方案为培美曲赛单药或联合铂类。入组的患者在基线及2周期治疗后采取外.周血进行粒细胞集落刺激因子(G-CSF),血管内皮生长因子A(VEGF-A)和血管内皮生长因子受体-2(VEGFR-2)检测。生物标志物和有效率的相关性分析采用logistic回归模型。结果45例患者提供了基线外周血标本,37例患者提供了2周期治疗后的血标本。对于主要研究终点,发现基线低水平G-CSF比高水平的患者具有更高的有效率(P=0.046)。基线高水平VEGF-A比低水平的患者倾向于更高的有效率(P=0.061)。血浆标志物与无进展生存时间之间无显著相关性。VEGF-A水平在2周期治疗后比基线有显著性的升高(P<0.001)。结论在晚期非鳞非小细胞肺癌中使用贝伐珠单抗联合化疗时,基线G-CSF水平与疗效显著相关,然而基线VEGF-A和VEGFR-2与疗效无显著相关性。G-CSF可能是一个较好的预测贝伐珠单抗抵抗的标志物,有待进一步的研究。 Objective To investigate the crrelaions between biomarkers and overall response to bevacizumab plus chemotherapy for patients with advanced ns-NSCLC.Methods Patients with advanced ns-NSCLC,who were asigned to bevacizumab plus chemotherapy,were eligible.According to investigators'decisions,chemotherapy regimens were pemetrexed plus pltinum or pemetrexed alone.Peripheral blood samples were collected at baseline and after 2nd cycle of therapy to analysis granulocyte colony-stimulating factor(G-CSF),vascular endothelial growth factor A(VEGF-A)and VEGF reeptor-2(VEGFR-2).Coreations between biomarkers and overall response rate(ORR)were asesed by using a Logistic regression model.Results Baseline blood samples were available from 45 patients,while samples after 2nd cycle were obtained from 37 patients.For the primary analys,patients with low baseline plasma G-CSF levels showed an improved ORR versus patients with high levels(P=0.046).Patients with high baseline plasma VEGF-A levels showed a trend toward improved ORR versus patients with low levels(P=0.061).No significant correlations were observed between tumor biomarkers and progression-free survival.VEGF-A levels changed significantly higher at 2nd cycle compared with baseline(P<0.001).Conclusion Baseline plasma G-CSF correlates signifcantly with response in patients with advanced ns-NSCLC treated with bevacizumab plus chemotherapy,while VEGF-A and VEGFR-2 did not.G-CSF may be a good candidate marker of resistance to bevacizumab therapy,which supports further testing.