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08-12-2013 | Article

VEGF biomarkers predict treatment outcomes in mRCC

Abstract

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medwireNews: Analysis of treatment-naïve patients with metastatic renal cell carcinoma (mRCC) has identified potential biomarkers of prognosis and response to treatment with sunitinib.

The post-hoc assessment of clinical trial participants found that plasma levels of vascular endothelial growth factor (VEGF)-A and interleukin (IL)-8 had prognostic value in mRCC, while levels of soluble VEGF receptor-3 (sVEGFR-3) and IL-8 correlated with treatment response.

The findings suggest that inhibition of angiogenesis and/or lymphangiogenesis mediated by the VEGF receptor family may contribute to the efficacy of sunitinib, say J Andrew Williams (Pfizer Oncology, San Diego, California, USA) and co-authors writing in Cancer Chemotherapy and Pharmacology.

The team obtained data on 63 patients with mRCC who had taken part in a phase III trial of oral sunitinib versus interferon (IFN)-α as first-line therapy. Blood samples were taken at baseline and again at the end of therapy.

Among patients receiving sunitinib, plasma levels of VEGF-A increased more than fourfold during treatment while IL-8 levels increased approximately twofold to threefold. Plasma levels of VEGF-C were virtually unchanged during treatment while sVEGFR-3 levels declined by approximately 50%.

Among patients given IFN-α, plasma IL-8 levels increased approximately twofold during treatment while levels of the other proteins were unchanged.

In both treatment groups, baseline levels of VEGF-A and IL-8 were significantly associated with overall survival (OS) and baseline VEGF-C levels were significantly associated with progression-free survival (PFS).

Additionally, in the subgroup of 33 sunitinib-treated patients, VEGF-A levels were associated with PFS and baseline sVEGFR-3 levels were associated with PFS and OS. Meanwhile, among the 30 IFN-α-treated patients, IL-8 levels were associated with PFS.

In multivariate analysis, baseline sVEGFR-3 and IL-8 remained independent predictors of OS in the sunitinib arm, while there were no independent predictors of outcome in the IFN-α arm.

Pharmacodynamic changes were not associated with PFS or OS for any plasma protein investigated, the authors remark.

They conclude: “Further predictive biomarker research is clearly warranted in mRCC, not only for sunitinib but also for other VEGF pathway inhibitors and for agents targeting other pathways.”

medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013

By Joanna Lyford, Senior medwireNews Reporter