Vascular endothelial growth factor D expression is a potential biomarker of bevacizumab benefit in colorectal cancer

• Published in: British journal of cancer Vol. 113; no. 1; pp. 37 - 45
• Main Authors: Weickhardt, A J, Williams, D S, Lee, C K, Chionh, F, Simes, J, Murone, C, Wilson, K, Parry, M M, Asadi, K, Scott, A M, Punt, C J A, Nagtegaal, I D, Price, T J, Mariadason, J M, Tebbutt, N C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30-06-2015; Nature Publishing Group
• Subjects: 692/699/67/1059/99; 692/699/67/1504/1885; 692/699/67/1857; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer Research; Capecitabine; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Drug Resistance; Epidemiology; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Humans; Mitomycin - administration & dosage; Molecular Medicine; Neoplasm Metastasis; Oncology; Translational Therapeutics; Vascular Endothelial Growth Factor D - metabolism; bevacizumab; prediction; colorectal cancer; VEGF; biomarkers
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2015.209

Background:
Bevacizumab prolongs progression-free survival (PFS) in patients with metastatic colorectal cancer. We analysed the protein expression levels of vascular endothelial growth factor (VEGF) ligands and receptors to determine their prognostic and predictive effects.
Methods:
We graded expression of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-R1, and VEGF-R2 to assess whether overexpression predicted bevacizumab resistance in samples from 268 of 471 patients randomised to capecitabine (C), capecitabine and bevacizumab (CB), or CB and mitomycin (CBM) in the MAX trial and extended the analysis to the CAIRO-2 population.
Results:
Patients with low expression of VEGF-D (0, 1+) benefited from bevacizumab treatment (PFS hazard ratio (HR) (C
vs
CB+CBM), 0.21; 95% CI, 0.08–0.55; overall survival (OS) HR, 0.35; 95% CI, 0.13–0.90). Patients with higher VEGF-D expression received less benefit (VEGF-D 2+ PFS HR, 0.67; 95% CI, 0.45–1.00; OS HR, 0.82; 95% CI, 0.52–1.30; VEGF-D 3+ PFS HR, 0.77; 95% CI, 0.50–1.17; OS HR, 1.28; 95% CI, 0.79–2.09) (
P
interaction <0.05). In CAIRO-2, there was no difference in PFS or OS according to VEGF-D expression.
Conclusions:
The predictive value of VEGF-D expression for bevacizumab may depend on the chemotherapy backbone used. Further evaluation is required before clinical utilisation.