Significant overall survival improvement in proliferative subtype ovarian cancer patients receiving bevacizumab
20 September 2018 (online)
We previously demonstrated that bevacizumab may differentially improve ovarian cancer progression-free survival (PFS) depending on TCGA molecular subtypes. Despite recent progress in the molecular biology of epithelial ovarian cancer, results have not yet translated into individualized treatment options. In the current study we correlated mature overall survival data with TCGA subtypes in ovarian cancer patients from the AGO-OVAR11 trial.
Whole genome DASL gene expression arrays were performed on FFPE tissues from the AGO OVAR11 trial. Patients were stratified into four TCGA molecular subtypes. Correlation between molecular subtype and the efficacy of randomly assigned therapy with bevacizumab was assessed.
Among all four TCGA suptypes, only patients with tumors of the proliferative subtype had a statistically significant benefit from the addition of bevacizumab to standard chemotherapy. Median PFS and OS of proliferative subtype patients was 22.17 and 52.43 months respectively if bevacizumab was added to standard chemotherapy but only 12.0 and 35.27 months in the control arm. Anti-angiogenic therapy resulted in a median PFS improvement of 10.2 months (HR 0.48, p = 0.002) and in a median improvement of overall survival (OS) of 17.2 months (HR 0.54, p = 0.021) among TCGA proliferative subtype patients. The remaining three non-proliferative subtypes showed no statistically significant improvement of PFS or OS after addition of bevacizumab.
We demonstrate for the first time significant OS benefit in patients with TCGA proliferative molecular subtype. Our findings may help to develop molecularly stratified treatment strategies and hold potential to ultimately improve outcome in patients with ovarian cancer.