Abstract
BackgroundVascular endothelial growth factor (VEGF)-targeted therapy is effective in patients with ovarian cancer. Whether adipose tissue (AT) could predict the efficacy of VEGF receptor (VEGFR) inhibitors in ovarian cancer is unknown. We aimed to evaluate the ability of distinct AT depots to predict the efficacy of apatinib, a VEGFR inhibitor, in recurrent ovarian cancers included in the AEROC trial.MethodsThe AEROC was a single-arm phase 2 trial of apatinib and oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer. Apatinib was administered continuously, and oral etoposide was administered every 21 days for a maximum of six cycles. This was a post hoc study based on the AEROC trial. Areas of visceral AT (VAT), subcutaneous AT (SAT), and intermuscular AT (IMAT) were measured using computed tomography scan at baseline to assess their association with the objective response rate, progression-free survival, and overall survival.ResultsOf the 35 treated patients, 31 patients with at least one post-baseline efficacy assessment by computed tomography scan were included in this study. After adjusting for apatinib exposure, high VAT (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.03–0.90, P = 0.037) and SAT (OR, 0.16; 95% CI, 0.03–0.87, P = 0.034) were significantly associated with a higher objective response rate. Further, decreased risks of disease progression and death were associated with high VAT (hazard ratio [HR], 0.39; 95% CI, 0.17–0.92, P = 0.031, and HR, 0.12; 95% CI, 0.04–0.40, P < 0.001, respectively), SAT (HR, 0.35; 95% CI, 0.15–0.83, P = 0.027, and HR, 0.24; 95% CI, 0.08–0.67, P = 0.007, respectively), and IMAT (HR, 0.20; 95% CI, 0.06–0.74, P = 0.016, and HR, 0.13; 95% CI, 0.03–0.62, P = 0.011, respectively).ConclusionsHigh areas of VAT, SAT, and IMAT were significantly associated with better outcomes in patients with platinum-resistant or platinum-refractory ovarian cancer who received VEGFR inhibitors. AT assessments may be valuable as patient-specific imaging biomarkers for predicting response to VEGFR inhibitors.Trial registrationClinicalTrials.gov identifier: NCT02867956.
Highlights
Vascular endothelial growth factor (VEGF)-targeted therapy is effective in patients with ovarian cancer
High areas of visceral AT (VAT), subcutaneous AT (SAT), and intermuscular AT (IMAT) were significantly associated with better outcomes in patients with platinum-resistant or platinum-refractory ovarian cancer who received VEGF receptor (VEGFR) inhibitors
adipose tissue (AT) assessments may be valuable as patient-specific imaging biomarkers for predicting response to VEGFR inhibitors
Summary
Vascular endothelial growth factor (VEGF)-targeted therapy is effective in patients with ovarian cancer. Whether adipose tissue (AT) could predict the efficacy of VEGF receptor (VEGFR) inhibitors in ovarian cancer is unknown. We aimed to evaluate the ability of distinct AT depots to predict the efficacy of apatinib, a VEGFR inhibitor, in recurrent ovarian cancers included in the AEROC trial. The vascular endothelial growth factor (VEGF) signaling pathway is the most widely studied angiogenic pathway in ovarian cancer. The addition of anti-angiogenic drugs to chemotherapy, including VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs), has shown clinical benefit in terms of progression-free survival (PFS) in patients with ovarian cancer, both in the upfront and recurrent settings [4, 5].
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