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

ESMO Open

article

C. Zhou¹  J. O’Connor²  A. Backen²  J.W. Valle⁴  J. Bridgewater⁵  C. Dive¹  G.C. Jayson² 

[1] CRUK Manchester Institute Cancer Biomarker Centre, University of Manchester;Division of Cancer Sciences, University of Manchester;Division of Radiotherapy and Imaging, Institute of Cancer Research;The Christie NHS Foundation Trust;University College Hospital Macmillan Cancer Centre

关键词: angiogenesis;    VEGF inhibitor;    response biomarker;    Tie2;    bile duct cancer;   

DOI  :  10.1016/j.esmoop.2022.100417

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

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 × 10−14). Using the 95% confidence interval for these two groups, we defined a vascular complete response (vCR) as a 24% reduction in pTie2 within 9 weeks; vascular no response (vNR) as a 7% increase in pTie2, and a vascular partial response (between these limits). vCR cediranib-treated patients had significantly improved progression-free survival (8.8 versus 7.5 months, restricted mean ratio 0.73, P = 0.012) and overall survival (18.8 versus 12.1 months, hazard ratio 0.49, P = 0.02). By integrating data across ovarian cancer, CRC and ABC, we show that (i) patients with vNR do not benefit from VEGFi and (ii) Tie2-defined vascular progression occurs sufficiently in advance of radiological progressive disease that changes in treatment could be offered to prevent clinical deterioration.Conclusion pTie2 is the first cross-tumour, generic VEGFi, vascular response biomarker to guide optimum use of VEGFi in clinical practice.

【 授权许可】

CC BY|CC BY-NC-ND