Ovarian cancer patients would greatly benefit from the discovery of a reliable IHC marker that could predict their response to the antiangiogenic drug bevacizumab. The angiogenesis inhibitor bevacizumab targets a molecule called VEGF-A , which is expressed as several isoforms with pro- and antiangiogenic characteristics, the most prominent of which is VEGF-A165b. Tumor susceptibility to antiangiogenic therapy may be defined by the equilibrium of VEGF-A isoforms, which is directly related to the tumor’s angiogenic capability.
Researchers analyzed the relationship between VEGF-A165b expression and the success of bevacizumab in treating patients with advanced ovarian cancer. VEGF-A165b expression was investigated using IHC in formalin-fixed paraffin-embedded tissues from 413 patients who participated in the ICON7 multicenter phase III study and who were treated with standard platinum-based chemotherapy with or without bevacizumab. Bevacizumab added to standard platinum-based chemotherapy significantly enhanced progression-free and overall survival in patients with low VEGF-A165b (HR: 0.727; 95% CI, 0.538-0.984; P = 0.039).
The addition of bevacizumab in patients with low VEGF-A165b expression improved 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), even after adjustment for known risk factors. Here, investigators showed for the first time that patients with advanced ovarian cancer who express low levels of VEGF-A165b, an antiangiogenic VEGF-A splice variation, may benefit more from treatment with bevacizumab than those who express higher levels of this splice variant. They expect that this unique biomarker may have direct clinical significance for guiding bevacizumab-related treatment decisions in advanced ovarian cancer patients and might be incorporated into regular diagnostics.
