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Clinical Trial
. 2015 Jun 30;113(1):37-45.
doi: 10.1038/bjc.2015.209.

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

A J Weickhardt, D S Williams, C K Lee, F Chionh, J Simes, C Murone, K Wilson, M M Parry, K Asadi, A M Scott, C J A Punt, I D Nagtegaal, T J Price, J M Mariadason, N C Tebbutt
Clinical Trial

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

A J Weickhardt et al. Br J Cancer. .

Abstract

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 2þ PFS HR, 0.67; 95% CI, 0.45–1.00; OS HR, 0.82; 95% CI, 0.52–1.30; VEGF-D 3þ PFS 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.

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Conflict of interest statement

Dr Tebbutt has received honoraria and worked in a consulting role for Roche. Dr Price has been an uncompensated member of Roche advisory boards. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
CONSORT diagram.
Figure 2
Figure 2
Kaplan–Meier curves for (A) PFS and (B) OS according to VEGF-D expression in unadjusted analyses.
Figure 3
Figure 3
Forest plots for (A) PFS and (B) OS for groups with different levels of VEGF-D expression. *Hazard ratio for all patients in the MAX trial, including those whose tumour samples were not analysed.
Figure 4
Figure 4
Kaplan–Meier curves for (A) PFS and (B) OS according to VEGF-R1 expression in analyses adjusted for multiple comparisons.
See this image and copyright information in PMC

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