Predictive value of angiogenic proteins in patients with metastatic melanoma treated with bevacizumab monotherapy.

The incidence of malignant melanoma is rising worldwide and survival for metastatic disease is still poor. Recently, new treatment options have become available. Still, predictive biomarkers are needed to optimise treatment for this patient group. In this study, we investigated the predictive value of 60 angiogenic factors in patients with metastatic melanoma treated with the anti VEGF-A antibody bevacizumab. Thirty-five patients were included in a clinical phase II trial and baseline serum samples were analysed by multiplex protein array. High serum concentration of Activin A was significantly associated with objective response to treatment (p=0.014). Candidate proteins that indicated a borderline association with treatment response were further investigated by immunohistochemistry. Strong expression of Activin A, Interleukin 1β and urokinase type Plasminogen activator receptor in metastases was significantly associated with objective response (p=0.011, p=0.003 and p=0.007, respectively), as well as with markers of activated angiogenesis, such as higher number of proliferating vessels and the presence of glomeruloid microvascular proliferations. Our findings indicate that these proteins may be potential predictive markers for treatment with bevacizumab monotherapy. This article is protected by copyright. All rights reserved.