Plasma Tie2 trajectories identify vascular response criteria for VEGF inhibitors across advanced biliary tract, colorectal and ovarian cancers.

BACKGROUND

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 AND METHODS

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.

RESULTS

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

CONCLUSION

pTie2 is the first cross-tumour, generic VEGFi, vascular response biomarker to guide optimum use of VEGFi in clinical practice.

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure JWV reports personal fees from Agios, AstraZeneca, Baxter, Genoscience Pharma, Hutchison Medipharma, Imaging Equipment Ltd (AAA), Incyte, Ipsen, Mundipharma EDO, Mylan, QED, Servier, Sirtex and Zymerworks; and grants, personal fees and non-financial support from NuCana, outside the submitted work. GCJ reports research funding from AstraZeneca for clinical trials outside of the submitted work. Research funding has been received from: AstraZeneca, Astex Pharmaceuticals, Bioven, Amgen, Carrick Therapeutics, Merck AG, Taiho Oncology, GSK, Bayer, Boehringer Ingelheim, Roche, BMS, Novartis, Celgene, Epigene Therapeutics Inc, Angle PLC, Menarini, Clearbridge Biomedics, Thermo Fisher Scientific and Neomed Therapeutics. CD has received honoraria for consultancy/advisory boards from Biocartis, Merck and AstraZeneca. All other authors have declared no conflicts of interest.