Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial

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Backen, Alison C. and Lopes, Andre and Wasan, Harpreet and Palmer, Daniel H. and Duggan, Marian and Cunningham, David and Anthoney, Alan and Corrie, Pippa G. and Madhusudan, Srinivasan and Maraveyas, Anthony and Ross, Paul J. and Waters, Justin S. and Steward, William P. and Rees, Charlotte and McNamara, Mairéad G. and Beare, Sandy and Bridgewater, John A. and Dive, Caroline and Valle, Juan W. (2018) Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial. British Journal of Cancer . ISSN 0007-0920

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Abstract

BACKGROUND: Advanced biliary tract cancer (ABC) has a poor prognosis. Cediranib, in addition to cisplatin/gemcitabine [CisGem], improved the response rate, but did not improve the progression-free survival (PFS) in the ABC-03 study. Minimally invasive biomarkers predictive of cediranib benefit may improve patient outcomes.

METHODS: Changes in 15 circulating plasma angiogenesis or inflammatory-related proteins and cytokeratin-18 (CK18), measured at baseline and during therapy until disease progression, were correlated with overall survival (OS) using time-varying covariate Cox models (TVC).

RESULTS: Samples were available from n=117/124 (94%) patients. Circulating Ang1&2, FGFb, PDGFbb, VEGFC, VEGFR1 and CK18 decreased as a result of the therapy, independent of treatment with cediranib. Circulating VEGFR2 and Tie2 were preferentially reduced by cediranib. Patients with increasing levels of VEGFA at any time had a worse PFS and OS; this detrimental effect was attenuated in patients receiving cediranib. TVC analysis revealed CK18 and VEGFR2 increases correlated with poorer OS in all patients (P< 0.001 and P=0.02, respectively).

CONCLUSIONS: Rising circulating VEGFA levels in patients with ABC, treated with CisGem, are associated with worse PFS and OS, not seen in patients receiving cediranib. Rising levels of markers of tumour burden (CK18) and potential resistance (VEGFR2) are associated with worse outcomes and warrant validation.

Item Type: Article
RIS ID: https://nottingham-repository.worktribe.com/output/939694
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Cancer and Stem Cells
Identification Number: https://doi.org/10.1038/s41416-018-0132-8
Depositing User: Eprints, Support
Date Deposited: 21 Jun 2018 10:24
Last Modified: 04 May 2020 19:41
URI: https://eprints.nottingham.ac.uk/id/eprint/52543

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