Soluble CD87 (s-uPAR) predicts bevacizumab-based first line treatment of metastatic colorectal cancer (mCRC): Results from a prospective multi-center study.

Abstract

604 Background: Bevacizumab-combined chemotherapy is well established in the induction treatment of metastatic colorectal cancer (mCRC). Despite tremendous efforts, no valid predictive marker for anti-VEGF treatment has so far been defined. CD87, the urokinase plasminogen activator receptor (uPAR), is centrally regulating VEGF-induced angiogenesis via adapting endothelial cell migration and invasion (Unseld et al.; ThrombHaem,2015, Brunner et al.; Blood 2011, Prager et al; Blood 2009; Prager et al; Blood 2004). Preoperative plasma s-uPAR levels were shown to independently predicted survival of patients resectable colorectal cancer. This study aimed to identify any prognostic or predictive value of s-uPAR in front-line bevacizumab-treated mCRC patients. Methods: In this prospective multi-center trial (NCT02119026), patients were either treated with bevacizumab plus FOLFOX or bevacizumab plus FOLFIRI. Baseline s-uPAR levels were assessed in 80 patients (40 ea. group) using respective CE-certified electro-chemiluminescence immunoassay (ECLIA). Biomarkers were explored using Kaplan-Meier curves and were log transformed for survival analysis by Cox proportional hazards models. All P values reported are two-sided. Results: Data from eighty patients were available for analysis. Progression free survival (PFS) and overall survival (OS) were assessed. Data indicate significance for the angiogenic biomarker uPAR to determine prognostic (HR = 3.06, CI 1.45 - 6.53, p = 0.003) and predictive (HR = 3.41, CI 2.03 - 5.74, p < 0.001) value in the treatment of Bevacizumab. Conclusions: This is the first prospective analysis of baseline s-uPAR. High baseline-s-uPAR levels were an independent predictive marker for worse bevacizumab-based first-line treatment response.