Table 2a Anti-VEGF antibodies and circulating biomarkers

From: Biomarkers of angiogenesis and their role in the development of VEGF inhibitors

References

Drug, disease and trial

Biomarkers

N

Drug-induced changes

Prognostic and predictive values

Dowlati et al (2008)

Carboplatin and Paclitaxel±

Bevacizumab

NSCLC (E4599); Phase 2/3

VEGF

E-selectin

FGF-2

ICAM

160

↓E-selectin

↑FGF-2

Baseline VEGF predicts response (P=0.01)

-Low baseline VEGF: better PFS (P=0.04)

-Low ICAM: better OS (P=0.00005),1 year survival and high RR (P=0.02)

Siegel et al (2008)

Bevacizumab

Unresectable HCC

Phase 2

VEGF

SDF-1

HUVEC

8

↓VEGF and SDF-1

↓HuVEC angiogenic score

↑VEGF and SDF-1 on progression

-VEGF and SDF-1 levels correlate with angiogenic score

Yang et al (2003)

Bevacizumab mRCC; Phase 2

VEGF

113

↑VEGF

NS

Nimeiri et al (2008)

Bevacizumab+Erlotinib

Recurrent ovarian cancer

Phase 2

sVEGFR-2

Urine VEGF

11

NS

NS

Ko et al (2008)

Gemcitabine+Cisplatin+Bevacizumab

Pancreatic cancer; Phase 2

VEGF

FGF-2

46

↑VEGF

↑FGF-2

NS

Garcia et al (2008)

Cyclophosphamide+Bevacizumab

Ovarian cancer; Phase 2

VEGF

E-selectin

TSP-1

70

↑VEGF and ↓TSP-1

NS

Denduluri et al (2008)

Bevacizumab

Breast cancer

Pilot study

VEGF

sVCAM-1 sVEGFR-2

21

↑sVCAM-1

↑sVEGFR-2

NS

Varker et al (2007)

Bevacizumab±IFNα-2b

Malignant melanoma

Phase 2

VEGF

FGF-2

32

NS

NS

Yao et al (2008)

Octreotide+INFα-2b+ Bevacizumab

NET; Phase 2

FGF-2

IL-8

36

↓FGF-2

↑ IL-8

NS

Jayson et al (2005)

HuMV833

Advanced cancer

Phase 1

VEGFR-1, IL-8, sVCAM-1, FGF-2, E-selectin, HGF

20

↑VEGF

↓FGF, HGF

NS

Dellapasqua et al (2008)

Cyclophosphamide+Capecitabine+ Bevacizumab

Breast cancer; Phase 2

CEC

CEPC

46

↓CEC

High baseline CECs correlate with OR (P=0.02), clinical benefit (P=0.01) and improved PFS (P=0.04)

Willett et al (2005)

Chemoradiotherapy+Bevacizumab

Rectal cancer; Phase 1

CEC

CEPC

6

↓CEC/CEPC

NS

  1. Abbreviations: VEGF=vascular endothelial growth factor; CEC=circulating endothelial cell; CEPC=circulating endothelial progenitor cell; FGF-2=fibroblast growth factor-2; HCC=hepatocellular carcinoma; HGF=hepatocyte growth factor; HUVEC=human umbilical vein endothelial cell; ICAM=intercellular adhesion molecule; INFα-2b=interferon α-2b; mRCC=metastatic renal cell carcinoma; NET=neuroendocrine tumour; NS=not significant; NSCLC=non-small-cell lung cancer; OR=overall response; OS=overall survival; RR=response rate; SDF-1=stromal cell-derived factor-1; sVCAM=soluble vascular cell adhesion molecule; sVEGFR-2=soluble VEGF receptor 2; TSP-1=thrombospondin-1.
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