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RESEARCH PRODUCT

Angiogenesis biomarker study of a phase II trial of pazopanib (P) in recurrent or persistent ovarian (EOC), peritoneal (PPC), or fallopian tube cancer (FTC): A Spanish Ovarian Cancer Group (GEICO) study.

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e15575 Background: Angiogenesis is essential to tumor growth, invasion, and metastasis in EOC. The aim of this study was to identify angiogenic biomarkers to predict response to P, a potent and selective multi-targeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-a/β, and c-kit, in a clinical phase II trial. Methods: We analyzed a series of 20 out of 25 women enrolled in a GEICO Phase II trial that studied the Clinical Benefit Rate (CBR) of P in platinum-resistant EOC, PPC and FTC (results will be presented in an additional abstract). Formalin-fixed, paraffin-embedded tumors at diagnosis were evaluated for the microvessel density (MVD) by using CD31 immunostaining and the Image Pro-Plus 7.0 Image Analysis System (Media-Cybernetics). In addition, several angiogenic factors were evaluated by means of immunohistochemistry (IHC) on tissue arrays sections, and quantitative real-time PCR (qRT-PCR) using the Human Angiogenesis Arrays (Applied Biosystems). Serum samples were also collected at different moments of the treatment schedule and a panel of 14 citokines and growth factors were evaluated using the Luminex technology (Millipore). Results: Fifteen (75%) of the tumors were high grade serous EOC. Eight patients (40%) showed a CBR on treatment.MVD analysis, (number of vessels/mm2) was 2025 (835-3242) and 2410 (1449-3543) in patients with and without CBR respectively (p=0.278). IHC showed very low expression of angiogenesis-related factors including VEGF and VEGFRs, PDGF and PDGFRs, HIF and pAKT. Expression analysis by qRT-PCR and serum levels of cytokines and growth factors revealed no statistical differences between patients with and without CBR. Conclusions: No predictive biomarkers of CBR to P in platinum-resistant EOC could be identified in a population of patients with low expression level of angiogenic factors at diagnosis.