The TICONC (Ticagrelor-Oncology) Study: Implications of P2Y12 Inhibition for Metastasis and Cancer-Associated Thrombosis

Joy R Wright; Meera Chauhan; Chirag Shah; Alistair Ring; Anne L Thomas; Alison H Goodall; David Adlam

doi:10.1016/j.jaccao.2020.04.009

The TICONC (Ticagrelor-Oncology) Study: Implications of P2Y₁₂ Inhibition for Metastasis and Cancer-Associated Thrombosis

JACC CardioOncol. 2020 Jun 16;2(2):236-250. doi: 10.1016/j.jaccao.2020.04.009. eCollection 2020 Jun.

Authors

Joy R Wright¹, Meera Chauhan^{1

2}, Chirag Shah¹, Alistair Ring³, Anne L Thomas², Alison H Goodall^{1

2}, David Adlam¹

Affiliations

¹ Department of Cardiovascular Sciences, University of Leicester, and the National Institutes of Health Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
² Leicester Cancer Research Centre, Department of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom.
³ Department of Medicine, Royal Marsden Hospital NHS Trust, London, United Kingdom.

Abstract

Background: In cancer, platelets may facilitate metastatic spread by a number of mechanisms as well as contribute to thrombotic complications. Ticagrelor, a platelet antagonist- that blocks adenosine diphosphate activation of platelet P2Y₁₂ receptors, is widely used in the treatment of cardiovascular disease, but its efficacy in cancer remains unknown.

Objectives: This study sought to evaluate the effect of aspirin and ticagrelor monotherapy, as well as dual antiplatelet therapy, on platelet activation in cancer.

Methods: This study consisted of 2 phases: first, an in vitro study of human platelet-tumor cell interaction; and second, a randomized crossover clinical trial of 22 healthy donors and 16 patients with metastatic breast or colorectal cancer. Platelet activation and inhibition were measured by aggregometry and flow cytometry.

Results: In vitro, tumor cells induced cellular clusters that were predominantly platelet-platelet aggregates. Ticagrelor significantly inhibited formation of large tumor cell-induced platelet-platelet aggregates: 65.4 ± 4.8% to 50.9 ± 5.9% (p = 0.002) and 62.3 ± 3.1% to 48.3 ± 7.3% (p = 0.014) for MCF-7 and HT-29-induced aggregation, respectively. Supporting this finding, cancer patients on ticagrelor had significantly reduced levels of spontaneous platelet aggregation and activation compared with baseline; 14.8 ± 2.7% at baseline to 7.8 ± 2.3% with ticagrelor (p = 0.012).

Conclusions: Our findings suggested that P2Y₁₂ inhibition with ticagrelor might reduce spontaneous platelet aggregation and activation in patients with metastatic cancer and merits further investigation in patients at high risk of cancer-associated thrombosis. (Ticagrelor-Oncology [TICONC] Study; EudraCT: 2014-004049-29).

Keywords: ADP, adenosine diphosphate; DAPT, dual antiplatelet therapy; TCIPA, tumor cell-induced platelet activation; aspirin; breast cancer; cancer-associated thrombotic risk; colorectal cancer; metastasis; platelets; ticagrelor.