Abstract
<h3>Introduction/Background</h3> The identification of a robust immunohistochemical marker to predict the response to bevacizumab in ovarian cancer is of high clinical interest. VEGF-A, the molecular target of bevacizumab, is expressed as multiple isoforms with pro- or anti-angiogenic properties, of which VEGF-A<sub>165</sub>b is the most dominant anti-angiogenic isoform. The balance of VEGF-A isoforms is closely related to the angiogenic capacity of a tumor and may define its vulnerability to anti-angiogenic therapy. We investigated, whether expression of VEGF-A<sub>165</sub>b is a predictive biomarker for bevacizumab treatment in advanced ovarian cancer. <h3>Methodology</h3> Formalin-fixed paraffin-embedded (FFPE) tissues from 413 patients of the ICON7 multicenter phase III trial, treated with standard platinum-based chemotherapy with or without bevacizumab, were probed for VEGF-A<sub>165</sub>b expression by immunohistochemistry. <h3>Results</h3> In patients with low VEGF-A<sub>165</sub>b expression, the addition of bevacizumab to standard platinum-based chemotherapy significantly improved progression-free (HR: 0.727, 95%CI=0.538 – 0.984; p=0.039) and overall survival (HR: 0.662, 95%CI=0.458 – 0.958; p=0.029). Multivariate analysis showed that the addition of bevacizumab in low VEGF-A<sub>165</sub>b expressing patients conferred significant improvements in progression-free survival (HR: 0.610, 95%CI=0.446 – 0.834; p=0.002) and overall survival (HR: 0.527, 95%CI=0.359 – 0.775; p=0.001), independently from established risk factors. <h3>Conclusion</h3> We demonstrate for the first time that immunohistochemical expression of the anti-angiogenic VEGF-A isoform, VEGF-A<sub>165</sub>b, is an independent predictor for bevacizumab treatment in ovarian cancer patients. We envision that this marker could be implemented into routine diagnostics in ovarian cancer and may guide clinical decisions related to bevacizumab treatment.
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