Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab‐based treatment response in metastatic colorectal cancer

Abstract

Carcinoembryonic antigen (CEA) affects tumorigenesis by enhancing tumor cell survival and by inducing tumor angiogenesis. This study aimed to evaluate baseline CEA serum levels to predict bevacizumab-based therapy effect and survival in patients with metastatic colorectal cancer (mCRC). Two hundred and ninety eight mCRC patients receiving chemotherapy plus either bevacizumab or cetuximab were analyzed in a retrospective study. Disease control (DC), progression-free survival (PFS), and overall survival were assessed and related to pretreatment CEA serum levels. Patients with baseline CEA serum levels below the statistical median of 26.8 ng/mL (group I) were compared with patients with higher CEA levels (group II). The cetuximab-based treatment cohort was analyzed for specificity assessment of CEA to predict the anti-vascular endothelial growth factor effect in mCRC. Baseline CEA serum levels inversely correlated with therapeutic response in patients receiving bevacizumab-based treatment (disease control rate, 84% vs 60%), inversely correlated with median PFS leading to a median PFS benefit of 2.1 months for patients in group I when compared with group II, as well as inversely correlated with median overall survival (37.5 months vs 21.4 months). In an independent cohort of 129 patients treated with cetuximab-based therapy, no association of therapeutic response or PFS with CEA serum levels was found. As expected, baseline CEA levels were prognostic for mCRC. These data give first evidence that baseline serum CEA levels might constitute an important predictor for the efficacy of first-line bevacizumab-based therapy in patients with mCRC.Previously, we found that CEA induces angiogenesis independent of VEGF. The data presented here now give first evidence that baseline serum CEA levels in patients might constitute an important predictor for the efficacy of first-line bevacizumab-based therapy for metastatic colorectal cancer.

Baseline carcinoembryonic antigen as a predictive factor of ramucirumab efficacy in RAISE, a second-line metastatic colorectal carcinoma phase III trial

“…Although the RAISE clinical trial demonstrated that ramucirumab improves median PFS and OS, not all patients benefited from ramucirumab-FOLFIRI therapy. Because recent reports have found evidence that baseline levels of CEA may be prognostic for patient survival and predictive of VEGFR-inhibitor treatment outcome [9,10], we explored CEA data from the RAISE trial.…”

“…Evidence compiled over several years indicates that elevated baseline serum CEA is an independent negative prognostic factor for mCRC [8]. More recent evidence suggests that baseline CEA inversely correlates with progression-free survival (PFS) and overall survival (OS) in patients undergoing first-line treatment [9,10]. Although the RAISE-predefined CEA subgroups did not exhibit any difference in efficacy results, ad hoc analyses were undertaken to explore other cutoff thresholds.…”

Avoiding hepatic metastasis naturally: Lessons from the cotton top tamarin (Saguinus oedipus)

“…Others have also suggested a relationship between CEA and angiogenesis though they did not establish it as causal or identify potential mechanisms [45,46] . Recently, however they showed that secreted (soluble) CEA can directly activate endothelial cells via integrin β3 signaling [24,47] . We suggest that an alternate mechanism may also exist involving the relationship between CEA and its receptor CEAR.…”

Molecular Markers Predictive of Chemotherapy Response in Colorectal Cancer

“…Recently, retrospective studies have suggested an association between carcinoembryonic antigen (CEA) levels and response to bevacizumab-based chemotherapy. Lower baseline CEA levels suggest a higher likelihood of treatment response and longer median PFS and OS [46, 47]. Prager et al assessed baseline CEA levels in a cohort of patients receiving first-line therapy with chemotherapy (FOLFOX, XELOX, FOLFIRI, or XELIRI) and bevacizumab and compared them to patients who received a cetuximab-based regimen.…”