VEGF-C serum level is associated with response to bevacizumab maintenance therapy in primary ovarian cancer patients

Abstract

Objective At present, maintenance therapy with the antiangiogenic agent bevacizumab or with PARPinhibitors represent two options for BRCA-wildtype ovarian cancer patients, after platinumbased first line chemotherapy. The identification of molecular markers to predict patient response to different maintenance therapies remains a major challenge. In the present study we analyzed the predictive potential of vascular endothelial growth factor C (VEGF-C) to identify ovarian cancer patients that might benefit from an antiangiogenic therapy. Methods 101 patients with primary epithelial ovarian cancer were analyzed for serum levels of VEGFA,- C and CA-125 by ELISA. Serum levels were compared between patients with low pTstage (pT1a-pT2c n = 11), healthy individuals (n = 27) and patients with higher pT-stage (> = pT3 n = 90). Adjusted ROC curves and an adjusted logistic regression model were carried out to evaluate the potential impact of VEGF-A and -C, as well as CA-125 serum level concentration on bevacizumab-therapy response, under consideration of covariates such as FIGO, pM, pN and residual tumor after surgery. Results A patient which has in comparison twice the VEGF-C concentration in serum, has a significant increased chance of response to bevacizumab by a factor of 2.79. Further, only VEGF-C serum levels were significantly higher in the group of patients with lower pTstage compared to healthy individuals, whereas VEGF-A or CA-125 serum levels could not discriminate between healthy individuals and patients with ovarian cancer at low pTstages. Conclusion VEGF-C serum level might serve as as a biomarker to evaluate treatment response under bevacizumab.