Multiple Genetic Alterations To Predict The Clinical Outcome For Bevacizumab Plus Chemotherapy In Advanced Ovarian Cancer: A Retrospective Study.

e17037 Background: Bevacizumab(BV) plus chemotherapy is widely used in patients with advanced ovarian cancer(OC). However, there was not predict biomakers to determined the use of BV-based treatment in OC currently.Therefore, exploring the predict biomarkers for BV is imperative. Methods: Tumor issues of advanced OC treated with BV plus chemotherapy were used for next generation sequencing (NGS) with a 150-gene targeted panel. The correlation between Progression-Free Survival (PFS) and genes or clinicopathology features was analyzed by Kaplan-Meier or Cox regression. For multivariate Cox regression, all factors with a p-value < 0.05 in univariate Cox regression were included. The potential predictive genes would be analyzed with VEGF-related signatures by using 374 OC mRNA data from The Cancer Genome Atlas (TCGA).Statistical analysis was performed using GraphPad Prism and SPSS. Results: 62 Chinese advanced OC patients treated with BV-base therapy were enrolled in this study from May 2015 to March 2018.The median PFS of these patients was 5.7 months , while ORR and DCR rate was 14.5% and 96.8%, repecitively.Patients with EGFR or HER2 alterations had poorer PFS compared with wild-type (EGFR,4.2 months vs. 7.4 months,p = 0.019;HER2,3.8 months vs. 7.3 months, p = 0.045), while MYC amplification patients got better PFS than MYC wild-type patients(17.4 months vs. 6.0 months,p = 0.049). However, in multivariate Cox regression anlysis, EGFR and HER2 were significantly correlated with PFS(P < 0.001 and p = 0.016,respectively),and MYC amplification seemed to have a positive trend(p = 0.052).Moreover,patients with HER2 alterations has a poorer OS(p = 0.008).The VEGF-related signatures analysis results indicated EGFR variants may upregulated VEGFA expression to induced resistant of BV,while downregulation of HIF was significantly correlated with MYC amplification,which was beneficial to efficacy of BV.HER2 alterations has not correlated with VEGF pathways,suggesting HER2 was a poor prognosis of OC instead of an negative predictor of BV. Conclusions: NGS is an effective method to reveal the potential predictor for BV plus chemotherapy in advanced ovarian cancer, and the patients with EGFR or HER2 alterations should consider alternative regimens such as anti-EGFR or anti-HER2 target therapy instead of BV-based regimens.