Relationship of angiogenesis biomarkers and clinical response to bevacizumab (Bev) in persistent or recurrent epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC) patients treated in a Phase II Gynecologic Oncology Group study

Abstract

21021 Background: Angiogenesis promotes tumor growth and is associated with poor outcomes in ovarian cancer. Currently, there are no markers to predict or determine response to anti-angiogenesis therapies. Methods: Persistent or recurrent EOC/PPC patients (1–2 prior cytotoxic regimens, measurable disease, and GOG performance status = 2) were treated with Bev (15mg/kg IV q21days) until progression. Tissue biopsies, serum samples and dynamic contrast enhanced MRIs (DC-MRI) were obtained prior to initiation (PT01) and 4th cycle (PT02) of Bev therapy. Tumor vascular endothelial growth factor (VEGF), thrombospondin-1 (TSP-1), and mutant p53 were determined by immunohistochemistry (IHC) and scored using histoscore (HS) analysis ([1 + staining score (0 to 4)] x % positive). Microvessel density (MVD) was determined by counting CD31 IHC hot spots. Serum VEGF levels were obtained by ELISA. Variables were considered as continuous or discontinuous in this training set to establish appropriate cut points to be applied to an ongoing phase III trial (GOG218). Results: From 4/02 to 8/04, 62 eligible patients were enrolled. A 17.7% response rate with 40% of patients with no evidence of disease progression for at least 6 months was previously reported (ASCO 2005). 44 tissue samples from PT01 and 27 from PT02 were evaluable for IHC biomarker levels. Based on current analysis, VEGF HS average was 92 at low MVD counts, while at high MVD counts, VEGF HS average was higher at 159 (p=0.06). In addition, 77% of TSP-1 negative tissues were VEGF positive, while 52% of TSP-1 positive tissues were VEGF positive. Analysis of serum VEGF levels (from 56 PT01 and 39 PT02 specimens) and DCMRIs (49 PT01 and 42 PT02 MRIs) are ongoing. Conclusions: Higher tumorVEGF was associated with increased angiogenesis and lower TSP-1 tissue levels. Results from the biomarkers tested await correlation to the mature survival data which should be available by June 2007. We plan to determine whether an angiogenesis biomarker profile is associated with patient response to Bev therapy. No significant financial relationships to disclose.