P-238 - Circulating epidermal growth factor-like domain 7 of prognostic importance in patients with metastatic colorectal cancer

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter T. Hansen
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors T. Hansen, D. Olsen, F. Sørensen, A. Jakobsen
  • Vejle Hospital, Vejle/DK

Abstract

Introduction

The number of available treatment regimens containing anti-angiogenic drugs is constantly growing calling for the identification of predictive biomarkers. Epidermal growth factor-like domain 7 (EGFL7) is a key regulator of the angiogenic process responsible for vascular tube formation, vascular integrity, and for the guiding of migrating endothelial cells during the sprouting process. The aim of the present study was to analyse the relationship between circulating EGFL7 and clinical outcome in patients with metastatic colorectal cancer (mCRC) treated with first line capecitabine and oxaliplatin (XELOX), and bevacizumab.

Methods

The study included 89 patients with mCRC. Serum samples collected at base-line, after three weeks of treatment, and at progression were analysed. The enzyme-linked immunosorbent assay method was used for the analyses of EGFL7. All samples were assayed in duplicate and the average was used for comparison with clinical data. The total coefficients of variation on two levels were 19.2% (high) and 23.4% (low). Protein concentrations are expressed in ng/ml. Clinical response was evaluated according to RECIST version 1.0. The association between categorical outcomes and the EGFL7 concentrations was analysed using the Wilcoxon Rank-Sum Test for differences in medians. Progression free survival (PFS), and overall survival (OS), was compared using the Kaplan-Meier method and the log rank test, and patients were classified according to EGFL7 concentrations at base-line (low, intermediate, and high).

Results

Circulating EGFL7 at base-line was predictive for OS. Median OS for patients with high base-line concentrations was 11.8 months (95% confidence interval (CI), 8.8-15.6 months), 18.4 months (95% CI, 13.2-21.6 months) in the intermediate group, and 22.7 months (95% CI, 16.5-30.6 months) in the low group, respectively, p = 0.001. The unfavourable prognosis for patients with high levels of circulating EGFL7 at base-line was independent of performance status, prior tumour resection, and number of metastatic sites when analysed in a Cox Regression multiple analyses, hazard ratio 2.53 (95% CI 1.23-5.21), p = 0.01. Base-line concentrations (medians) of EGFL7 were significantly lower in patients that post treatment underwent resections of their metastases (R0 resections), 143 ng/ml (95% CI, 68-225 ng/ml), N = 16, compared to the remaining patients, N = 73, that remained unresectable, 336 ng/ml (95% CI, 195-514 ng/ml), p = 0.01. Circulating EGFL7 was not related to response and PFS.

Conclusion

The present results, based on serial blood samples, confirm previous findings from studies addressing tumour tissue, all suggesting unfavourable clinical outcome for patients with high concentrations of EGL7. The results thus support the potential of targeting EFGL7, from a therapeutic point of view, in patients with mCRC.