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

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).

SUBMITTER: Wright JR 

PROVIDER: S-EPMC8352224 | biostudies-literature |

REPOSITORIES: biostudies-literature