2022-RA-211-ESGO Expression of the anti-angiogenic VEGF-A splice variant, VEGF-A₁₆₅b, as predictive biomarker for bevacizumab treatment in advanced ovarian cancer patients

Introduction/Background

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-A₁₆₅b 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-A₁₆₅b is a predictive biomarker for bevacizumab treatment in advanced ovarian cancer.

Methodology

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-A₁₆₅b expression by immunohistochemistry.

Results

In patients with low VEGF-A₁₆₅b 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-A₁₆₅b 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.

Conclusion

We demonstrate for the first time that immunohistochemical expression of the anti-angiogenic VEGF-A isoform, VEGF-A₁₆₅b, 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.