Original article
A snapshot of cancer-associated thromboembolic disease in 2018–2019: First data from the TESEO prospective registry

https://doi.org/10.1016/j.ejim.2020.05.031Get rights and content

Highlights

  • We present a snapshot of CAT in the era of immunotherapy and targeted therapies.

  • Thrombotic risk is dynamic related to specific oncological contexts.

  • The epidemiology and evolution of CAT is changing in recent years.

  • Clinicians should factor in the thrombotic potential of targeted therapies.

Abstract

Background

The ever-growing complexity of cancer-associated thrombosis (CAT), with new antineoplastic drugs and anticoagulants, distinctive characteristics, and decisions with low levels of evidence, justifies this registry.

Method

TESEO is a prospective registry promoted by the Spanish Society of Medical Oncology to which 34 centers contribute cases. It seeks to provide an epidemiological description of CAT in Spain.

Results

Participants (N=939) with CAT diagnosed between July 2018 and December 2019 were recruited. Most subjects had advanced colon (21.4%), non-small cell lung (19.2%), and breast (11.1%) cancers, treated with dual-agent chemotherapy (28.4%), monochemotherapy (14.4%), or immune checkpoint inhibitors (3.6%). Half (51%) were unsuspected events, albeit only 57.1% were truly asymptomatic. Pulmonary embolism (PE) was recorded in 571 (58.3%); in 120/571 (21.0%), there was a concurrent deep venous thromboembolism (VTE). Most initially received low molecular weight heparin (89.7%). Suspected and unsuspected VTE had an OS rate of 9.9 (95% CI, 7.3-non-computable) and 14.4 months (95% CI, 12.6-non-computable) (p=0.00038). Six-month survival was 80.9%, 55.9%, and 55.5% for unsuspected PE, unsuspected PE admitted for another reason, and suspected PE, respectively (p<0.0001). The 12-month cumulative incidence of venous rethrombosis was 7.1% (95% CI, 4.7-10.2) in stage IV vs 3.0% (95% CI, 0.9-7.1) in stages I-III. The 12-month cumulative incidence of major/clinically relevant bleeding was 9.6% (95% CI, 6.1-14.0) in the presence of risk factors.

Conclusion

CAT continues to be a relevant problem in the era of immunotherapy and targeted therapies. The initial TESEO data highlight the evolution of CAT, with new agents and thrombotic risk factors.

Introduction

Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with cancer [1]. Both pathologies interrelate at a deep biological level with numerous interactions between key elements of the hemostatic system and cancer cell programs [2]. Cancer-associated thrombosis (CAT) falls within a panorama of growing complexity in oncology, with the appearance of new anticoagulant therapies, emerging molecular data [3], and new antineoplastic treatments associated with thrombotic risk. Most targeted therapies that have proven benefit in recent clinical trials, such as CDK4/6 inhibitors, immune checkpoint inhibitors, or antiangiogenics, are linked to increased risk of VTE [4], [5], [6]. Managing CAT is challenging, given the higher risk of rethrombosis and severe bleeding with anticoagulant treatment [7]. Moreover, people with cancer exhibit numerous specific characteristics, such as the use of chemotherapy, hormone therapy, or targeted therapies with specific mechanisms of action and toxicities, increased incidental thrombosis, and chronic comorbidities (hepatic, renal, thrombocytopenia, etc.) that add an extra layer of complication to decision-making.

Despite the multiple clinical practice guidelines regarding the prevention and management of CAT, numerous critical decisions about anticoagulant therapy, primary thromboprophylaxis, or management of special cases continue to be made with low levels of evidence [8]. The problem is exacerbated, in light of the high percentage of these patients who will not be eligible or will be under-represented in clinical trials, given the complexity of their clinical situation [9].

The Spanish Society of Medical Oncology's (SEOM) registry of thrombosis and embolism [TESEO] was born in 2018 to detect emerging epidemiological trends in CAT and to analyze outcomes in real-world clinical practice of cases that run the gamut from ordinary to the most highly complex and exceptional (e.g., those with high risk of bleeding, incidental episodes, etc.). With these premises, we present the first data coming out of the TESEO registry (NCT03855592) that provide a prospective snapshot of CAT (2018-2019).

Section snippets

Patients and study design

TESEO is a prospective registry under the auspices and management of SEOM with the collaboration of 34 Spanish hospitals that recruit consecutive cases of CAT [10].

Eligibility criteria consist of individuals ≥18 years of age with cancer, with a VTE event confirmed by objective imaging technique (Doppler ultrasound, CT angiography scans, high probability scintigraphy, CT scheduled to assess tumor response or for other reasons, etc.). In the case of multiple episodes, only the first event is

Variables and objectives

The aim of this study is to provide an epidemiological description of CAT in Spain. The study variables included clinical and molecular characteristics of the neoplasms, VTE-associated variables, prognostic evaluation of the episodes, and anticoagulant therapy. The study endpoints comprise overall survival, 15-day complication rate, venous rethrombosis, and bleeding. Overall survival (OS) was defined as the time since development of VTE and all-cause mortality, bearing in mind the

Patients and oncological context

At the time of analysis, 939 patients diagnosed with VTE between July 2018 and December 2019 had been recruited. The baseline characteristics of these individuals are summarized in Table 1. The most common tumors were high incidence ones: colorectal (n=201, 21.4%), non-small cell lung (n=181, 19.2%), and breast (n=105, 11.1%), followed by of other neoplasms associated with high thrombotic risk (pancreas, stomach, ovary, etc.) (see detailed list in A.1).

Most had an active tumor or stage IV

Discussion

This analysis describes the situation of CAT during the 2018-2019 period, based on the initial data from the SEOM's registry of thrombosis, TESEO. The reason for undertaking this project has been the perception that cancer treatment is developing at breakneck speed, with transformations that force us to reassess aspects having to do with support [16], re-think the thrombotic risk of new survivors [17], as well as the effect new antitumor drugs have on hemostasis [4], [5], [6]. Added to that is

Funding

The study has been funded by a restricted grant from Sanofi, S.A. This entity has not contributed to the study design, data analysis, interpretation of the results, drafting of the document, or in the decision regarding publication in any way.

Research involving human participants

All procedures followed are in accordance with the ethical standards of the committee in charge of human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions.

Informed consent or a substitute for it was obtained from all patients before they were included in the study.

CRediT authorship contribution statement

Alberto Carmona-Bayonas: Formal analysis, Writing - original draft, Writing - review & editing. David Gómez: Formal analysis, Writing - original draft, Writing - review & editing. Eva Martínez de Castro: Formal analysis, Writing - original draft, Writing - review & editing. Pedro Pérez Segura: Formal analysis, Writing - original draft, Writing - review & editing. José Muñoz Langa: Formal analysis, Writing - original draft, Writing - review & editing. Paula Jimenez-Fonseca: Formal analysis,

Declaration of Competing Interest

ACB: consulting/advisory role: Roche, Rovi, Sanofi, LeoPharma, Pfizer, Esteve; travel grants: Ipsen, Roche, Novartis. DG: None. EMC: Consultant or Advisory Role: Pfizer, Amgen. Speaking: Roche, Pfizer, Amgen, Sanofi, LeoPharma, Rovi, Celgene. Travel, Accommodations: Roche, Pfizer, Celgene, Sanofi. PPS: Consultant or Advisory Role: Novartis, BMS, Merck. Travel, Accommodations: MSD, Merck. JML: Consultant or Advisory Role: LEO Pharma. Speaking: Sanofi, LeoPharma. Travel, Accommodations:

Acknowledgments

SEOM for sponsoring this study. Priscilla Chase Duran for editing and translating the manuscript. The mFAR team for the support of the website registry.

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