Haematology-Oncology Department, Basil Hetzel Institute,The Queen Elizabeth Hospital, Woodville, SA, Australia.
Int J Cancer. 2014 Aug 1;135(3):731-41. doi: 10.1002/ijc.28698. Epub 2014 Jan 24.
Tumor biomarkers to more accurately predict a patient's response to a given therapy are much needed in oncology practice. For metastatic colorectal cancer the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab is now commonly included in first-line therapy regimens and has led to modest but significant improvements in patient outcomes compared with chemotherapy. Given the modest gains there is a pressing need for predictive biomarkers to better identify patients who would benefit from this targeted therapy. We used a multiplex protein assay to determine the tumor expression levels of the proangiogenic proteins IL-6, IL-8, bFGF, PDGF-BB and VEGF-A in formalin-fixed paraffin-embedded tumors from the MAX clinical trial patients with available tissue samples. Patients were dichotomized into "low" vs. "high" expression subgroups based on median baseline levels to correlate with objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). "Low" tumor VEGF-A level was predictive of better ORR for bevacizumab [ORR (low) 53% vs. (high) 19%, interaction p = 0.03] but not for PFS [hazard ratio, HR (low) 0.73 vs. (high) 0.62, interaction p = 0.68] in the comparison of capecitabine (C) versus C and bevacizumab (CB) and CB plus mitomycin (M). When analyzed as a dichotomized variable, "high" VEGF-A was prognostic for shorter PFS (unadjusted HR 1.34, p = 0.06; adjusted HR 1.55, p = 0.008). The other four proteins were neither predictive of bevacizumab benefits nor prognostic for ORR, PFS or OS. "Low" tumor VEGF-A was associated with longer PFS after adjustment for other baseline factors. Proangiogenic proteins were not predictive of benefit with bevacizumab for PFS.
在肿瘤学实践中，非常需要肿瘤标志物来更准确地预测患者对特定治疗的反应。对于转移性结直肠癌，抗血管内皮生长因子（VEGF）单克隆抗体贝伐珠单抗现在通常包含在一线治疗方案中，与化疗相比，患者的预后有了适度但显著的改善。鉴于这种适度的获益，迫切需要预测性生物标志物来更好地识别那些将从这种靶向治疗中获益的患者。我们使用多重蛋白检测法来确定 MAX 临床试验中可获得组织样本的患者的福尔马林固定石蜡包埋肿瘤中的促血管生成蛋白 IL-6、IL-8、bFGF、PDGF-BB 和 VEGF-A 的肿瘤表达水平。根据基线中位数将患者分为“低”和“高”表达亚组，以与客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）相关联。肿瘤 VEGF-A 水平低与贝伐珠单抗的更好 ORR 相关（ORR（低）为 53%，而（高）为 19%，交互 p = 0.03），但与 PFS 无关（风险比，HR（低）为 0.73，而（高）为 0.62，交互 p = 0.68），在卡培他滨（C）与 C 和贝伐珠单抗（CB）和 CB 加丝裂霉素（M）的比较中。当作为二分类变量进行分析时，“高”VEGF-A 是 PFS 较短的预后因素（未调整 HR 为 1.34，p = 0.06；调整 HR 为 1.55，p = 0.008）。其他四种蛋白既不能预测贝伐珠单抗的获益，也不能预测 ORR、PFS 或 OS。在调整其他基线因素后，肿瘤 VEGF-A 水平低与 PFS 延长相关。促血管生成蛋白与贝伐珠单抗的 PFS 获益无关。
