Plasma Tie2 trajectories identify vascular response criteria for VEGF inhibitors across advanced biliary tract, colorectal and ovarian cancers
Vascular endothelial growth factor inhibitors (VEGFi) are compromised by a lack of validated biomarkers. Previously we showed that changes in the concentration of plasma Tie2 (pTie2) was a response biomarker for bevacizumab. Here, we investigated whether pTie2 can predict response and progression cross-tumour for generic VEGFi treatment. Patients (n = 124) with advanced biliary tract cancer (ABC) received cisplatin/gemcitabine with cediranib or placebo (ABC-03 trial). Concentrations of pTie2 were measured longitudinally from before treatment until disease progression. Data from patients with ovarian cancer (n = 92, ICON7 trial) and patients with colorectal cancer (CRC) (n = 70, Travastin trial) were also included. Cediranib-treated ABC patients were deconvoluted into distinct groups where in one group pTie2 trajectories resembled those seen in placebo-treated patients and in another pTie2 significantly reduced (t-test P = 2.7 × 10 pTie2 is the first cross-tumour, generic VEGFi, vascular response biomarker to guide optimum use of VEGFi in clinical practice.
Journal
ESMO OpenAuthors
Funding
Cancer Research UK Grant C5759/A27412Cancer Research UK Grant 29832Cancer Research UK Grant C2930/A11428Department of Health FundingCancer Research UK Grant C480/A15578GlaxoSmithKline FundingNovartis FundingRoche FundingBoehringer Ingelheim FundingBayer FundingCancer Research UK Grant CRUK/09/029British Microcirculation Society FundingAmgen FundingServier FundingAstraZeneca FundingAstex Pharmaceuticals FundingManchester Biomedical Research Centre Funding