Predictive Biomarkers in Metastatic Colorectal Cancer Patients Treated With Bevacizumab: A Turkish Oncology Group (TOG) Study

Abstract

Efforts to improve outcomes for patients with metastatic colorectal cancer (mCRC) treated with bevacizumab are limited by the lack of validated predictive biomarkers. To overcome this challenge, our study prospectively assessed the combined prognostic and predictive significance of circulating angiogenic biomarkers and T-cell subsets. Eighty-eight patients with unresectable mCRC were prospectively enrolled. Pre-treatment serum levels of VEGF, bFGF, PDGF-B, and endothelin-1 (ET-1) were measured by ELISA, nitric oxide by colorimetric assay, and T-cell subsets by flow cytometry. Bevacizumab trough levels and anti-bevacizumab antibodies were assessed by ELISA. Higher baseline levels of proangiogenic factors, including VEGF, PDGF-B, and ET-1, were associated with improved survival. Based on these findings, we developed a novel Angiogenesis Index (AI) using the cut-off values for VEGF, PDGF-B, and ET-1. This AI was a significant predictor of efficacy for bevacizumab-based therapy for both PFS and OS. Furthermore, bevacizumab trough levels exceeding 25 mu g/mL on day 14 were associated with improved OS. Likewise, patients with lower baseline circulating FoxP3+ regulatory T cells (Treg) tended to have improved survival. The AI, bevacizumab trough levels, and baseline Treg levels are promising biomarkers for predicting efficacy and refining patient selection for bevacizumab therapy in mCRC.