VEGF-A splicing variant in plasma is a predictive potential biomarker of bevacizumab in advanced non-squamous non-small cell lung cancer

J Chemother. 2025 Dec 26:1-9. doi: 10.1080/1120009X.2025.2605782. Online ahead of print.

ABSTRACT

Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor-A (VEGF-A), a key mediator of tumor angiogenesis. Among VEGF-A splice variants, VEGF-A_xxxa has proangiogenic activity, whereas VEGF-A_xxxb exerts anti-angiogenic effects. Recent methodological advances have enabled accurate quantitative assessment of the plasma VEGF-A_xxxa, defined as the proportion of VEGF-A_xxxa relative to total VEGF-A. In this study, we evaluated the predictive potential of the VEGF-A_xxxa ratio for bevacizumab efficacy in patients with non-squamous non-small cell lung cancer treated with carboplatin and paclitaxel with or without bevacizumab. A higher VEGF-A_xxxa ratio (≥0.45) was associated with significantly longer progression-free survival and overall survival in the bevacizumab-treated group, with statistically significant treatment interactions. These results suggest that the plasma VEGF-A_xxxa ratio may serve as a minimally invasive biomarker with potential utility for predicting clinical benefit from bevacizumab.

PMID:41454602 | DOI:10.1080/1120009X.2025.2605782