Use of Anticoagulants of Patients with Cancer-Associated Thrombosis Beyond 6 Months ; The Uscat Study, a 432-Patient Retrospective Non-Interventional Study
Authors: Mahe Isabelle , Plaisance Ludovic , Chapelle Céline , Laporte Silvy , Planquette Benjamin , Bertoletti Laurent , Chidiac Jean , Couturaud Francis , Falchiero Lionel , Falvo Nicolas , Mahé Isild , Helfer Hélène , Meyer Guy 
Published: November 2019

Introduction
Few data are available about the treatment and complications beyond 6 months and up to 12 months in Cancer-associated Thrombosis (CAT) patients initially treated with low-molecular-weight (LMWH). Study objectives were to document the prescription and use of the anticoagulant treatment beyond 6 months and up to 12 months in CAT patients initially treated with tinzaparin and to measure clinical outcomes.
Methods
Adult CAT patients with solid tumor, previously included in 2 prospective cohort studies (AXA - NCT02898051; PREDICARE - NCT03099031) and still alive at the end of the initial 6-month treatment period with tinzaparin were eligible to participate in this retrospective non-interventional French multicenter study.
Main study outcome was the description of the anticoagulant treatment in the management of CAT patients in usual medical care from the 6th month to the 12th month.
Secondary objectives included the incidence of VTE recurrence, bleeding and deaths. A sample size of 250 to 300 patients was considered appropriate to allow analyses of 6-to-12-month data post-index event based on descriptive statistics.
Results
A total of 432 patients aged 66.5±12.7 years of whom 52.1% female alive at the end of AXA and PREDICARE 6-month treatment period were included in this retrospective study; 332 patients were followed up to 12 months while 96 patients deceased before the end of the study and 4 patients were lost-to-follow-up.
Most patients (91.9%) had a single-site cancer. Cancers were mostly solid tumors and primary sites were colorectal (21.6%), lung (20.1%) or breast (16.8%); a proportion of 82.1% of patients had stage III or IV malignancy while cancer was progressing in 51.2% of patients.
Beyond 6 months, the anticoagulant treatment was maintained in 290 of 421 (68.9%) patients of whom 241 (83.1% [95% CI: 78.3%; 87.2%]) patients were treated with a LMWH and 233 (80.3%) with tinzaparin, 32 (11.0%) and 13 (4.5%) patients were treated with vitamin K antagonists (VKA) and direct oral anticoagulants (DOAC), respectively. The anticoagulant treatment was discontinued in 131 of 421 (31.1%) patients of whom 63 patients had already stopped the anticoagulant before 6 months while 68 patients stopped the anticoagulant treatment at 6 months. Mean treatment duration with LMWH beyond 6 months was 121.6 ± 65.6 days representing a mean total treatment duration of 288.4 ± 85.0 days since the index event.
Between 6 and 12 months, 24 (5.7%) patients experienced a VTE recurrence corresponding to a cumulative incidence of 8% [95% CI: 4.2%; 15.1%], while 11 (2.7%) patients had a major bleeding corresponding to a cumulative incidence of 2.6% [95% CI: 1.3%; 5.1%]. VTE recurrence was more frequent in patients with colorectal and lung cancer while major bleeding was more frequent in patients with colorectal cancer (Table) A total of 96 (22.3%) deaths corresponding to a cumulative incidence of 30.7% [95% CI: 22.3%; 30.7%] were reported of which 55 (12.8%) related to cancer, 1 (0.2%) to bleeding and 8 (1.9%) to another cause while the cause of death was not documented for 32 (7.5%) patients. Clinical outcomes according the type of cancer are summarized in the Table.
Conclusion
These results reporting the clinical course up to 12 months of a large cohort of patients still alive at the end of the initial 6-month period following the VTE index event, provide data contributing to the clinician's therapeutic decision when facing a patient completing 6 months of anticoagulant for a CAT. Site of cancer has to be taken into account when assessing the risk of subsequent VTE recurrence and bleeding.

Disclosures
Mahe: BMS: Research Funding, Speakers Bureau; Pfizer: Speakers Bureau; LEO Pharma: Research Funding, Speakers Bureau; Bayer: Speakers Bureau. Laporte:Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees; Leo-Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boston scientific: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Bertoletti:Sanofi: Research Funding, Speakers Bureau; BMS-Pfizer: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Aspen: Consultancy, Speakers Bureau. Couturaud:Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Falchiero:Astra-Zeneca: Consultancy; MSD: Consultancy; Boehringer Ingelheim: Speakers Bureau; BMS: Speakers Bureau; Amgen: Consultancy; Roche: Speakers Bureau. Falvo:Medtronic: Consultancy; Toshiba: Consultancy; Leo-Pharma: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; BMS: Consultancy; Bayer: Consultancy. Meyer:Bayer: Other: travel support; Boehringer Ingelheim: Research Funding; LEO pharma: Other: travel support, Research Funding; SANOFI: Other: travel support, Research Funding; BMS-Pfizer: Other: travel support, Research Funding.