VEGF biomarkers predict treatment outcomes in mRCC
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.”
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By Joanna Lyford, Senior medwireNews Reporter