Abstract 1122
Background
Platelet activation by tumour cells contributes to critical steps in the formation of metastases. Mechanisms include protection of tumour cells from immune destruction, interaction of platelet receptors with tumour ligands to facilitate adhesion, and enrichment of the tumour microenvironment to promote extravasation and proliferation. This study investigated the differences in platelet activation markers in cancer patients compared to healthy donors, and the effect of the addition of in vitro antiplatelet agents.
Methods
Blood was collected from consented healthy volunteers and patients with metastatic cancer. Platelet rich plasma was prepared. Light transmission aggregometry measured spontaneous aggregation of platelet samples, without the addition of exogenous agonists. Flow cytometry measured the platelet activation markers P-selectin and fibrinogen binding on unstimulated, untreated platelets, and on unstimulated platelets incubated with aspirin, Ticagrelor and dual antiplatelet therapy.
Results
62 cancer patients and 17 healthy donors provided blood samples. There was increased spontaneous aggregation of platelets from cancer patients compared to healthy platelets (9±1.1% vs 4±0.9% p = 0.02). Platelets from cancer patients had increased basal levels of P-selectin expression compared to healthy platelets (17.2±2.7% vs 8.4±0.3%) and incubation of platelets with antiplatelets had no effect. There was no difference in the basal level of fibrinogen binding between populations, however incubation with dual antiplatelet therapy reduced baseline fibrinogen binding in platelets from cancer patients (3.1±0.7% vs 10.8±3.7%).
Conclusions
Platelets from cancer patients are hyperactive and easily form aggregates compared to healthy platelets. Platelets from cancer patients have higher levels of the activation marker P-selectin. Aggregation requires fibrinogen binding and incubation with dual antiplatelet therapy reduces this binding in platelets from cancer patients. The interaction between tumour cells and platelets could be a potential biomarker of disease, and this is reduced by antiplatelet drugs. Further studies determining the effect of in vivo antiplatelet therapy on platelets in cancer patients are being undertaken.
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
5389 - Two-weekly accelerated BEP (aBEP) regimen as induction chemotherapy (CT) in intermediate and poor prognosis patients (pts) with nonseminomatous germ cell tumors (NSGCT): final results of phase II trial.
Presenter: Alexey Tryakin
Session: Poster Display session 3
Resources:
Abstract
2934 - Differential expression of circulating miR375 and miR371 to detect teratoma and viable germ cell malignancy
Presenter: Lucia Nappi
Session: Poster Display session 3
Resources:
Abstract
3585 - Prognosis of anaemia in disseminated testicular germ cell tumours. On behalf of the Spanish Germ Cell Cancer Group (SGCCG)
Presenter: Esmeralda Garcia Torralba
Session: Poster Display session 3
Resources:
Abstract
2254 - The Effects Of Primary Testicular Tumor Localization On Prognosis In Patients With Nonseminomatous Testis Cancer
Presenter: Birol Yildiz
Session: Poster Display session 3
Resources:
Abstract
4505 - Initial Results of a Phase II study of Nivolumab and Ipilimumab in Metastatic Adrenal Tumors.
Presenter: Matthew Campbell
Session: Poster Display session 3
Resources:
Abstract
3369 - NEMIO: a randomized phase II trial evaluating efficacy and safety of dose dense MVAC (ddMVAC) + durvalumab +/- tremelimumab as neoadjuvant treatment in patients with bladder muscle-invasive urothelial carcinoma
Presenter: Constance Thibault
Session: Poster Display session 3
Resources:
Abstract
2075 - KEYNOTE-866: Phase 3 Study of Perioperative Pembrolizumab (pembro) or Placebo (pbo) in Combination With Neoadjuvant Chemotherapy in Cisplatin (cis)-Eligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
4824 - KEYNOTE-905: A Phase 3 Study of Cystectomy Plus Perioperative Pembrolizumab Versus Cystectomy Alone in Cisplatin (cis)-Ineligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Matthew Galsky
Session: Poster Display session 3
Resources:
Abstract
2253 - Phase 3 LEAP-011 trial: First-Line Pembrolizumab With Lenvatinib in Patients With Advanced Urothelial Carcinoma Ineligible to Receive Platinum-Based Chemotherapy
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
4310 - PULSE : A Single Arm Trial Assessing The Activity and Safety of Avelumab Immunotherapy Maintenance among Patients With Locally Advanced or Metastatic Squamous Cell Penile Carcinoma (mSCPC).
Presenter: Noemie Gassian
Session: Poster Display session 3
Resources:
Abstract