Background: Vascular endothelial growth factors (VEGFs) are key regulators of tumor angiogenesis. RAM, a recombinant human IgG1 monoclonal antibody specific for VEGF receptor 2 (VEGFR2), inhibits VEGF-A, -C and -D binding to VEGFR2 and inhibits ligand-induced mitogenesis of human endothelial cells. We evaluated candidate tumor (HER2, VEGFR2) and serum (VEGF-C, -D, and soluble [s] VEGFR1 and 3) biomarkers for correlation with overall survival (OS) and progression-free survival (PFS) in patients from the randomized phase 3 REGARD trial (NCT00917384) that demonstrated survival benefits for RAM vs. PL. Methods: Of 355 patients randomized to RAM or PL in REGARD, there was at least one evaluable biomarker result for 152 (43%) patients using VEGFR2 immunohistochemistry (IHC) or HER2 (IHC or fluorescence in situ hybridization [FISH]) in baseline tumor tissue samples. For 32 (9%) patients, baseline serum samples were analyzed using VEGF-C, -D, sVEGFR1 or 3 validated assays. Assay analyses were blinded. Results: The table provides the results of the HER2 analyses in tumor tissue (N = 147) and VEGFR2 analyses in tumor blood vessels (N = 143). The small number of patients with serum samples limited interpretation for candidate circulating biomarkers. Conclusions: Exploratory candidate biomarker analysis of tumor biopsies and serum from REGARD patients did not identify a significant predictive marker for RAM efficacy. Further examination of the role of VEGFR2 pathway biomarkers is warranted in ongoing RAM trials. Clinical trial information: NCT00917384

Note: Treatment-by-VEGFR2 interaction p-values, not adjusted for multiplicity, were 0.878 for mOS and 0.051 for mPFS. Abbreviations: CI=confidence interval; HR=hazard ratio; m=median. ^aBang et al. 2010 criteria. ^bin months. ^cHigh= ≥ median H-score (35); low= <35.