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

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.