Impact of Prior Bevacizumab Treatment on VEGF-A and PlGF Levels and Outcome Following Second-Line Aflibercept Treatment: Biomarker Post Hoc Analysis of the VELOUR Trial
Impact of Prior Bevacizumab Treatment on VEGF-A and PlGF Levels and Outcome Following Second-Line Aflibercept Treatment: Biomarker Post Hoc Analysis of the VELOUR Trial
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既往贝伐珠单抗治疗对 VEGF-A 和 PlGF 水平以及二线阿柏西普治疗后结果的影响：VELOR 试验的生物标志物事后分析
DOI：
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发表时间：
2019
影响因子：
11.5
通讯作者：
J. Tabernero
中科院分区：
文献类型：
--
作者：
E. Van Cutsem;C. Paccard;M. Chiron;J. Tabernero
目的：afLibercept是一种靶向抗血管内皮生长因子疗法，用于治疗奥沙利铂方案进展后的转移性结直肠癌(MCRC)患者。这项特别的研究在天鹅绒III期试验中评估了先前的贝伐单抗治疗和生长因子水平对与afLibercept相关的患者预后的影响。实验设计：采用基于微珠的多重分析方法测量基线生物标记物的血浆浓度。根据既往贝伐单抗治疗、二线治疗和血清生物标记物浓度对患者进行分组，并分析总生存期(OS)和无进展生存期(PFS)。结果：有553名患者可获得血浆样本(安慰剂n=265；安慰剂n=288)，其中169人以前接受贝伐单抗治疗。9个与血管生成或贝伐单抗耐药有关的生物标记物与先前的贝伐单抗治疗相关。与未接受贝伐单抗治疗的患者相比，接受贝伐单抗治疗的患者中，血管内皮生长因子-A和胎盘生长因子(PlGF)的升高最为显著。在安慰剂组中，与基线水平较低的患者(9.6个月比12.9个月)相比，基线水平较高的血管内皮生长因子-A(>；144 pg/ml)患者的OS和PFS更差。这也见于接受安慰剂并有较高基线PlGF的患者(>；8pg/ml；9.7个月对11.7个月)。在afLibercept组，无论基线VEGF-A或PlGF水平如何，OS和PFS均延长。结论：血清中高水平的VEGF-A和PlGF可能是mCRC患者对贝伐单抗产生耐药性的原因。无论基线的血管内皮生长因子-A和平台生长因子水平如何，afLibercept都能保持其活性，并且可能是贝伐单抗诱导耐药患者的有效二线治疗方法。
Purpose: Aflibercept is a targeted anti-VEGF therapy used to treat patients with metastatic colorectal cancer (mCRC) following progression on oxaliplatin-based regimens. This post hoc study evaluated the effect of prior bevacizumab treatment and growth factor levels on patient outcomes associated with aflibercept in the VELOUR phase III trial. Experimental Design: Baseline biomarker plasma concentrations were measured using a bead-based multiplex assay. Patients were grouped according to prior bevacizumab treatment, second‐line treatment, and serum biomarker concentrations, and analyzed for overall survival (OS) and progression-free survival (PFS). Results: Plasma samples were available for 553 patients (placebo n = 265; aflibercept n = 288), of which 169 had received prior bevacizumab. Nine biomarkers implicated in angiogenesis or bevacizumab resistance correlated with prior bevacizumab therapy. VEGF-A and placental growth factor (PlGF) were the most significantly increased in patients who had received prior bevacizumab compared with those who had not received prior bevacizumab. In the placebo group, patients with high VEGF-A (>144 pg/mL) levels at baseline had worse OS and PFS compared with patients with lower levels at baseline (9.6 vs. 12.9 months). This was also seen in patients who received placebo and had high baseline PlGF (>8 pg/mL; 9.7 vs. 11.7 months). In the aflibercept group, prolonged OS and PFS were observed regardless of baseline VEGF-A or PlGF levels. Conclusions: High VEGF-A and PlGF serum levels may underlie development of resistance to bevacizumab in patients with mCRC. Aflibercept retains its activity regardless of baseline VEGF-A and PlGF levels and may be an effective second-line treatment for patients with bevacizumab-induced resistance.
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影响因子：
--
作者：
Gonzalez-Pons M;Cruz-Correa M
通讯作者：
Cruz-Correa M
影响因子：
8.8
作者：
Schiffmann LM;Fritsch M;Gebauer F;Günther SD;Stair NR;Seeger JM;Thangarajah F;Dieplinger G;Bludau M;Alakus H;Göbel H;Quaas A;Zander T;Hilberg F;Bruns CJ;Kashkar H;Coutelle O
通讯作者：
Coutelle O
影响因子：
45.3
作者：
Kopetz, Scott;Hoff, Paulo M.;Heymach, John V.
通讯作者：
Heymach, John V.
影响因子：
45.3
作者：
Willett, Christopher G.;Duda, Dan G.;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.
影响因子：
158.5
作者：
Yang, JC;Haworth, L;Rosenberg, SA
通讯作者：
Rosenberg, SA