1129 - Aspirin and Ticagrelor for the prevention of tumour cell induced platelet aggregation

Background

Tumour cell induced platelet aggregation (TCIPA) increases the metastatic potential of cancer. Mechanisms include protection of tumour cells from immune destruction, interaction of platelet receptors with tumour ligands to facilitate adhesion, enrichment of the tumour microenvironment to promote tumour cell extravasation and proliferation. Reducing these interactions using antiplatelet agents could reduce metastatic progression. This study investigated the effect of Ticagrelor and aspirin on TCIPA in metastatic breast and colorectal cancer patients, compared to healthy controls.

Methods

Participants in this randomised, crossover study received aspirin or Ticagrelor for 2 weeks, followed by 2 weeks washout and crossover to the other monotherapy, before completing 2 weeks of dual therapy. Platelet rich plasma was prepared from blood samples at each time point. Light transmission aggregometry measured spontaneous aggregation of the platelets over 30 minutes without the addition of exogenous agonists. Flow cytometry measured the activation markers P-selectin and fibrinogen binding on unstimulated platelets.

Results

20 healthy, 10 breast and 6 colorectal cancer participants completed the study. Untreated platelets from colorectal patients had higher spontaneous aggregation (14.8±2.6%) than breast cancer (8.7±1%) or healthy platelets (8.1±0.9% p = 0.007). This was reduced by Ticagrelor (7.7±3.3% p = 0.01). Untreated platelets from patients with colorectal cancer had higher expression of P-selectin compared to platelets from healthy donors (14.2±1.3% vs 21.5±3.6% p = 0.03). Untreated platelets from breast patients had increased fibrinogen binding (49.5±7.8%) compared to healthy platelets (31.4±4.2% p = 0.03). This was reduced by Ticagrelor (26.7±5.2% p = 0.04) and dual therapy (31.4±6.9% p = 0.01).

Conclusions

This study demonstrated that platelets from breast and colorectal cancer patients are hyperactive compared to healthy donors. Ticagrelor reduces aggregation in platelets from patients with colorectal cancer, and as monotherapy and dual therapy can reduce platelet activation in patients with breast cancer. The pilot study indicates Ticagrelor may reduce TCIPA in cancer patients and could be used to decrease metastatic spread.

Clinical trial identification

EudraCT: 2014‐004049‐29, Start date:10‐03‐2015.

Editorial acknowledgement

Legal entity responsible for the study

University of Leicester.

Funding

AstraZeneca.

Disclosure

A. Thomas: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. A. Goodall: Research grant / Funding (institution): Hoffmann La Roche; Research grant / Funding (institution): AstraZeneca. D. Adlam: Research grant / Funding (institution): Abbott Vascular Inc; Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.