Relevance of baseline carcinoembryonic antigen for first-line treatment against metastatic colorectal cancer with FOLFIRI plus cetuximab or bevacizumab (FIRE-3 trial)
2019
PURPOSE: 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. EXPERIMENTAL DESIGN: FIRE-3 evaluated first-line
FOLFIRIplus
cetuximab(
FOLFIRI/Cet) versus
FOLFIRIplus
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. RESULTS: Of 400 patients, 356 (89.0%) were evaluable for CEA. High CEA (\textgreater10 ng/ml; N = 237) compared to low CEA (\textless/=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 {\textless} 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). CONCLUSION: 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
bevacizumabarm, while this was not the case when
cetuximabwas applied. Comparison of OS and objective response rate according to treatment arms indicated that
cetuximabwas greatly superior to
bevacizumabin patients with elevated CEA, while this effect was markedly lower and lost statistical significance in patients with low CEA.
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