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
4600 - Patterns and outcomes related to rapid progressive disease in a cohort of advanced solid tumors treated with immune checkpoint inhibitors (ICIs).
Presenter: Lucio Ghiglione
Session: Poster Display session 3
Resources:
Abstract
3547 - Real World Outcomes of Immune-Related Adverse Events (irAEs) among Patients Receiving Immune Checkpoint Inhibitors (ICIs) in Hospital Settings
Presenter: Saby George
Session: Poster Display session 3
Resources:
Abstract
1124 - Sex-based heterogeneity of efficacy of anticancer immunotherapy
Presenter: Fabio Conforti
Session: Poster Display session 3
Resources:
Abstract
4133 - Comparative efficacy and safety of PD-1/PD-L1 inhibitors for patients with solid tumors: a systematic review and Bayesian network meta-analysis
Presenter: Qingyuan Huang
Session: Poster Display session 3
Resources:
Abstract
2548 - Excess weight and efficacy of anti-PD-1 antibodies in advanced cancer patients
Presenter: Jacobo Rogado
Session: Poster Display session 3
Resources:
Abstract
2228 - Safety and efficacy of anti-PD-1 inhibitor ABBV-181 in lung and head and neck carcinoma
Presenter: Antoine Italiano
Session: Poster Display session 3
Resources:
Abstract
2333 - Efficacy and safety of immune checkpoint inhibitors (ICIs) for treatment of advanced solid tumours in octogenarian patients
Presenter: Soraya Mebarki
Session: Poster Display session 3
Resources:
Abstract
4847 - Association of programmed cell death 1 (PD-1) inhibitor therapy with overall survival (OS) in stage IV melanoma treated with targeted therapies
Presenter: Aracelis Torres
Session: Poster Display session 3
Resources:
Abstract
2215 - Clinical outcomes of immune checkpoint inhibitors in older and younger patients with advanced solid tumours in a real-life setting
Presenter: Pauline Corbaux
Session: Poster Display session 3
Resources:
Abstract
2881 - Impact of corticosteroids and antibiotics on efficacy of immune-checkpoint inhibitors in advanced non-small cell lung cancer
Presenter: Joaquin Mosquera Martinez
Session: Poster Display session 3
Resources:
Abstract