Low pre-therapeutic serum Ang-2 levels reduced the hazard of progression by 63% (HR 0.37) in metastatic colorectal cancer patients treated with bevacizumab-containing therapy.
Cohort (n=123)
Yes
Does low pre-therapeutic serum Ang-2 predict better clinical outcomes in metastatic colorectal cancer patients treated with bevacizumab-containing therapy?
Serum Ang-2 is a promising predictive biomarker for clinical outcomes in patients with metastatic colorectal cancer receiving bevacizumab-containing therapy.
Effect estimate: HR 0.37 (95% CI 0.17-0.80)
Absolute Event Rate: 14.1% vs 8.5%
p-value: p=0.01
BACKGROUND: The combination of chemotherapy with the vascular endothelial growth factor (VEGF) antibody bevacizumab is a standard of care in advanced colorectal cancer (CRC). However, biomarkers predicting outcome of bevacizumab-containing treatment are lacking. As angiopoietin-2 (Ang-2) is a key regulator of vascular remodelling in concert with VEGF, we investigated its role as a biomarker in metastatic CRC. METHODS: Serum Ang-2 levels were measured in 33 healthy volunteers and 90 patients with CRC. Of these, 34 had metastatic disease and received bevacizumab-containing therapy. To determine the tissue of origin of Ang-2, quantitative real-time PCR was performed on microdissected cryosections of human CRC and in a murine xenograft model of CRC using species-specific amplification. RESULTS: Ang-2 originated from the stromal compartment of CRC tissues. Serum Ang-2 levels were significantly elevated in patients with metastatic CRC compared with healthy controls. Amongst patients receiving bevacizumab-containing treatment, low pre-therapeutic serum Ang-2 levels were associated with a significant better response rate (82 vs 31%; P<0.01), a prolonged median progression-free survival (14.1 vs 8.5 months; P<0.01) and a reduction of 91% in the hazard of death (P<0.05). CONCLUSION: Serum Ang-2 is a candidate biomarker for outcome of patients with metastatic CRC treated with bevacizumab-containing therapy, and it should be further validated to customise combined chemotherapeutic and anti-angiogenic treatment.
Goede et al. (Fri,) conducted a cohort in Colorectal cancer (n=123). Low serum Angiopoietin-2 (<3.5 ng/ml) vs. High serum Angiopoietin-2 (≥3.5 ng/ml) was evaluated on Progression-free survival (months) (HR 0.37, 95% CI 0.17-0.80, p=0.01). Low pre-therapeutic serum Ang-2 levels reduced the hazard of progression by 63% (HR 0.37) in metastatic colorectal cancer patients treated with bevacizumab-containing therapy.
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