Department of Internal Medicine III, Comprehensive Cancer Center Munich, University Hospital Grosshadern, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377 Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich and German Cancer Research Centre (DKFZ), Heidelberg, Germany.
Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377 Munich, Germany.
Eur J Cancer. 2019 Jan;106:115-125. doi: 10.1016/j.ejca.2018.10.001. Epub 2018 Nov 27.
Increased baseline carcinoembryonic antigen (CEA) serum level is associated with inferior overall survival (OS) in metastatic colorectal cancer (mCRC). However, limited data exist on its predictive relevance for targeted therapies. Therefore, we analysed its relevance in FIRE-3, a randomised phase III study.
FIRE-3 evaluated first-line FOLFIRI plus cetuximab (FOLFIRI/Cet) versus FOLFIRI plus bevacizumab (FOLFIRI/Bev) in mCRC patients with RAS-WT tumour (i.e. wild-type in KRAS and NRAS exons 2-4). Herein, the impact of CEA on patient outcome was investigated.
Of 400 patients, 356 (89.0%) were evaluable for CEA. High CEA (>10 ng/ml; N = 237) compared to low CEA (≤10 ng/ml; N = 119) was associated with shorter OS in the FOLFIRI/Bev arm (hazard ratio [HR] = 1.50; P = 0.036), while no significant OS difference was observed in the FOLFIRI/Cet arm (HR = 1.07; P = 0.74). In patients with high CEA, FOLFIRI/Cet compared to FOLFIRI/Bev showed a greater OS benefit (HR = 0.56; P < 0.001) than in patients with low CEA (HR = 0.78; P = 0.30). Furthermore, FOLFIRI/Cet exhibited significantly superior objective response rate in patients with high CEA (odds ratio = 2.21; P = 0.006) in contrast to patients with low CEA (odds ratio = 0.90; P = 0.85).
In patients with RAS-WT mCRC receiving first-line chemotherapy with FOLFIRI/Cet versus FOLFIRI/Bev, elevated CEA was associated with inferior survival in the bevacizumab arm, while this was not the case when cetuximab was applied. Comparison of OS and objective response rate according to treatment arms indicated that cetuximab was greatly superior to bevacizumab in patients with elevated CEA, while this effect was markedly lower and lost statistical significance in patients with low CEA.
基线癌胚抗原（CEA）血清水平升高与转移性结直肠癌（mCRC）患者总生存期（OS）降低相关。然而，针对其靶向治疗预测价值的数据有限。因此，我们分析了 FIRE-3 研究中的相关性。
FIRE-3 评估了一线 FOLFIRI 联合西妥昔单抗（FOLFIRI/Cet）与 FOLFIRI 联合贝伐珠单抗（FOLFIRI/Bev）在 RAS-WT 肿瘤（即 KRAS 和 NRAS 外显子 2-4 野生型）mCRC 患者中的疗效。在此，研究了 CEA 对患者结局的影响。
在 400 例患者中，356 例（89.0%）可评估 CEA。高 CEA（>10ng/ml；N=237）与低 CEA（≤10ng/ml；N=119）相比，贝伐珠单抗组 OS 更短（风险比[HR]为 1.50；P=0.036），而西妥昔单抗组无显著 OS 差异（HR=1.07；P=0.74）。在高 CEA 患者中，FOLFIRI/Cet 与 FOLFIRI/Bev 相比，OS 获益更大（HR=0.56；P<0.001），而在低 CEA 患者中，OS 获益相似（HR=0.78；P=0.30）。此外，与低 CEA 患者相比（比值比[OR]为 0.90；P=0.85），高 CEA 患者接受 FOLFIRI/Cet 治疗的客观缓解率（OR=2.21；P=0.006）显著更高。
在接受一线 FOLFIRI/Cet 或 FOLFIRI/Bev 化疗的 RAS-WT mCRC 患者中，CEA 升高与贝伐珠单抗组的生存降低相关，而在应用西妥昔单抗时则不然。根据治疗臂比较 OS 和客观缓解率表明，在 CEA 升高的患者中，西妥昔单抗明显优于贝伐珠单抗，而在 CEA 较低的患者中，这种效果显著降低且失去统计学意义。
