Medline ® Abstract for Reference 87
of 'Systemic chemotherapy for nonoperable metastatic colorectal cancer: Treatment recommendations'
Vascular endothelial growth factor D expression is a potential biomarker of bevacizumab benefit in colorectal cancer.
Weickhardt AJ, Williams DS, Lee CK, Chionh F, Simes J, Murone C, Wilson K, Parry MM, Asadi K, Scott AM, Punt CJ, Nagtegaal ID, Price TJ, Mariadason JM, Tebbutt NC
Br J Cancer. 2015;113(1):37.
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, 1þ) benefited from bevacizumab treatment (PFS hazard ratio (HR) (C vs CBþCBM), 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 2þPFS HR, 0.67; 95% CI, 0.45–1.00; OS HR, 0.82; 95% CI, 0.52–1.30; VEGF-D 3þPFS HR, 0.77; 95% CI, 0.50–1.17; OS HR, 1.28; 95% CI, 0.79–2.09) (P interaction o0.05). 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.