Background: Recent data show high rates of venous and arterial thromboembolism (VTE/ATE) associated with targeted anti-cancer therapies.

Aims: We aim to provide comprehensive population-level data on absolute and relative risks of VTE/ATE in patients treated with immune-checkpoint-inhibitors (ICIs), multi-kinase-inhibitors (MKIs), VEGF-, HER-2-, EGFR-, and ALK-/ROS-targeted therapies.

Methods: Danish medical registries were used to identify 31,224 cancer patients treated with specific targeted therapies during 2004-2018. Cumulative VTE/ATE incidence after targeted treatment initiation was computed using competing-risk analysis. Relative risk of VTE was evaluated using conditional logistic regression in a case-control analysis, separately assessing exposure to targeted treatments within 3 months and at any time before VTE. VTE cases within cancer types were matched (4:1-ratio) by age, sex, cancer diagnosis year, and index date to controls without VTE. Multivariable adjustment was performed for cancer stage, comorbidities, and time from cancer diagnosis to index date.

Results: Cumulative 1-year risk of VTE were highest for anti-EGFR (6.3% [95%CI: 5.8-6.9]), anti-VEGF (6.0% [5.6-6.5]), and ICI-treatment (5.7% [4.9-6.7]). Corresponding risks of ATE were highest for anti-ALK/ROS-therapy (3.6% [1.3-7.7]), ICIs (2.2% [1.7-2.8]), and MKIs (1.9% [1.4-2.4]) (Table 1).

Cumulative incidence at 3, 6, 12, and 24 months of venous thromboembolism (VTE, comprising deep vein thrombosis and/or pulmonary embolism) and arterial thromboembolism (ATE, comprising ischaemic stroke, myocardial infarction, and acute peripheral arterial occlusion) in preselected targeted anti-cancer agent groups in competing risk analysis, accounting for all-cause mortality as a competing outcome event.
In lung cancer, VTE risk was associated with recent ICIs (odds ratio (OR): 1.45 [1.01–2.07]) and anti-EGFR-therapy (OR: 2.12 [1.65–2.73]). VTE risk was associated with recent ICI exposure in melanoma (OR: 6.48 [3.07–13.65]. Colorectal cancer patients had elevated VTE risk with recent anti-VEGF- (OR: 2.49 [2.09–2.97]) or anti-EGFR-treatment (OR: 3.33 [2.64–4.21]) (Table 2).

Matched case-control analysis using conditional logistic regression. Cases comprise adult patients with a given cancer diagnosis and subsequent VTE, and controls comprise adult patients with a given cancer without subsequent VTE. Matching of controls to cases in a 4:1 ratio was based on age, sex, year of cancer diagnosis, and year of index date (cases: VTE diagnosis date, controls: VTE diagnosis date of matched cases, with controls having to be alive and at risk on index date). Exposure was defined as treatment with a given targeted agent within 3 months prior to the index date (“recently exposed”) or at any time point prior to the index date (“ever exposed”). Multivariable adjustment was performed for tumour stage at diagnosis, Charlson Comorbidity Index score, and time from cancer diagnosis to index date.

Conclusions: In this nationwide analysis, we provide large-scale data for the first time on targeted anti-cancer therapies and VTE/ATE risk. The absolute thrombotic risk was substantial, and VTE-risk was relatively increased compared to controls for certain agent groups. These observations could allow identification of high-risk populations for thromboembolic events among cancer patients. Treatment data updated to 2020 will be presented at the meeting.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/risk-of-venous-and-arterial-thromboembolic-events-in-patients-receiving-targeted-anti-cancer-therapy-a-nationwide-cohort-study/