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

Alison Backen, Andre Lopes, Harpreet Wasan, Daniel H Palmer, Marian Duggan, David Cunningham, Alan Anthoney, Pippa G Corrie, Srinivasan Madhusudan, Anthony Maraveyas, Paul J Ross, Justin S Waters, William P Steward, Charlotte Rees, Mairead Mcnamara, Sandy Beare, John A Bridgewater, Caroline Dive, Juan Valle

Research output: Contribution to journalArticlepeer-review


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 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 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 a worse PFS and OS; not seen in patients receiving cediranib. Rising levels of markers of tumor burden (CK18) and potential resistance (VEGFR2) are associated with worse outcomes and warrant validation.
Original languageEnglish
JournalBritish Journal of Cancer
Publication statusPublished - 21 Jun 2018


  • angiogenesis
  • biomarkers
  • biliary-tract-cancer
  • cediranib
  • VEGF

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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