Adipose tissue area as a predictor for the efficacy of apatinib in platinum-resistant ovarian cancer: an exploratory imaging biomarker analysis of the AEROC trial

Xin Huang, Chuanbo Xie, Jie Tang, Wenzhuo He, Fan Yang, Wenfang Tian, Jundong Li, Qiuxia Yang, Jingxian Shen, Liangping Xia, Chunyan Lan, Xin Huang, Chuanbo Xie, Jie Tang, Wenzhuo He, Fan Yang, Wenfang Tian, Jundong Li, Qiuxia Yang, Jingxian Shen, Liangping Xia, Chunyan Lan

Abstract

Background: 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.

Methods: The 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.

Results: Of 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).

Conclusions: High 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 registration: ClinicalTrials.gov identifier: NCT02867956 .

Keywords: Intermuscular adipose tissue; Ovarian cancer; Subcutaneous adipose tissue; Vascular endothelial growth factor receptor; Visceral adipose tissue.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Representative axial CT images with respect to VAT, SAT, and IMAT. a The original CT image of AT and the segmentation of b VAT, c SAT, and d IMAT. CT, computed tomography; AT, adipose tissue; VAT, visceral AT; SAT, subcutaneous AT; IMAT, intermuscular AT
Fig. 2
Fig. 2
The Kaplan-Meier curves showing a progression-free survival and b overall survival in patients with low VAT and high VAT. VAT, visceral adipose tissue
Fig. 3
Fig. 3
The Kaplan-Meier curves showing a progression-free survival and b overall survival in patients with low SAT and high SAT. SAT, subcutaneous adipose tissue
Fig. 4
Fig. 4
The Kaplan-Meier curves showing a progression-free survival and b overall survival in patients with low IMAT and high IMAT. IMAT, intermuscular adipose tissue

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