Abstract 1129
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.
Resources from the same session
4021 - Prospective pathological experience with research biopsies in the context of clinical trials at Vall d’Hebron Institute of Oncology
Presenter: Paolo Nuciforo
Session: Poster Display session 3
Resources:
Abstract
5603 - Development of a comprehensive next-generation targeted sequencing assay for detection of gene-fusions in solid tumors
Presenter: Vinay Mittal
Session: Poster Display session 3
Resources:
Abstract
4952 - Next-generation sequencing for better treatment strategy of cancer of unknown primary (CUP)
Presenter: Kang Kook Lee
Session: Poster Display session 3
Resources:
Abstract
4590 - Circulating-free DNA analysis from long-term surviving metastatic colorectal cancer patients undergoing surgery for resectable disease.
Presenter: Michele Ghidini
Session: Poster Display session 3
Resources:
Abstract
3696 - Ultra-sensitive detection of circulating tumor DNA identifies patients in high risk of recurrence in early stages melanoma
Presenter: Filip Janku
Session: Poster Display session 3
Resources:
Abstract
4295 - Identification of the founder BRCA1 mutation c.4117G>T (p.Glu1373*) recurring in Abruzzo and Lazio regions of Central Italy and predisposing to breast/ovarian and BRCA1-related cancers
Presenter: Daniela Di Giacomo
Session: Poster Display session 3
Resources:
Abstract
2214 - Enzalutamide (ENZA) and Apalutamide (APA) In vitro chemical reactivity studies and Activity in a Mouse Drug Allergy Model (MDAM)
Presenter: Mausumee Guha
Session: Poster Display session 3
Resources:
Abstract
5044 - Influence of genetic variation in COMT on cisplatin-induced nephrotoxicity in cancer patients.
Presenter: Bram Agema
Session: Poster Display session 3
Resources:
Abstract
3293 - Cardioprotective and anti-inflammatory effects of Empagliflozin during treatment with Doxorubicin: a cellular and preclinical study
Presenter: Vincenzo Quagliariello
Session: Poster Display session 3
Resources:
Abstract
3324 - Breast Cancer Organoids Model Treatment Response of HER2 Targeted Therapy in HER2-mutant Breast Cancer
Presenter: Xuelu Li
Session: Poster Display session 3
Resources:
Abstract