CECs and IL-8 Have Prognostic and Predictive Utility in Patients with Recurrent Platinum-Sensitive Ovarian Cancer: Biomarker Correlates from the Randomized Phase-2 Trial of Olaparib and Cediranib Compared with Olaparib in Recurrent Platinum-Sensitive Ovarian Cancer

摘要

Objective Olaparib (O), a polyADPribose polymerase (PARP) inhibitor, and cediranib (C), a VEGF receptor (VEGFR)1–3 inhibitor together had greater activity than O alone in women with recurrent platinum-sensitive ovarian cancer (OvCa). The objective of this study is to identify potential lead biomarker candidates for response to O?+?C in the setting of a multi-institutional phase II study of O with and without C in recurrent platinum-sensitive OvCa. Methods A self-selected group of patients participated in a prospectively planned exploratory biomarker substudy of the randomized phase II study of O versus O?+?C. Whole blood for peripheral blood mononuclear cell (PBMC) and plasma isolation was collected prior to and on day 3 of treatment. Quantitation of circulating endothelial cells (CEC), IL-6, IL-8, VEGF, and soluble VEGFR-2 plasma concentrations, and polyADPribose (PAR) incorporation were performed. Single nucleotide polymorphism analysis of XRCC1 280H, R194W, and Q399R was done. Dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) was performed at baseline and day 3 of treatment. Parameter changes were compared between the two arms using an exact Wilcoxon rank sum test. Kaplan–Meier and log-rank tests were used to examine survival outcome. Results Thirteen patients elected to participate in the translational substudy, seven patients on O and six patients on O?+?C. Patients on O?+?C had a greater decrease in IL-8 concentration and larger CEC fold increase compared with those on O alone ( p ?=?0.026, p ?=?0.032). The fold increase in CEC on day 3 was associated with duration of progression-free survival (PFS) ( R ~(2)?=?0.77, 95% CI 0.55–0.97, p ?