By Lynda Williams, medwireNews Reporter
medwireNews: Use of targeted cancer therapies is associated with a clinically relevant increase in the risk of arterial and venous thromboembolic (ATE/VTE) events, indicate findings from a population-based cohort study.
“Our study has important clinical implications”, write Florian Moik (Medical University of Graz, Austria) and co-authors in eClinical Medicine, who say that the “substantial but heterogenous risk” identified among targeted therapy users “underscores the need for improved and treatment-specific cardiovascular surveillance and prevention strategies.”
The team collated information from a Danish database for 512,432 patients diagnosed with cancer between 2004 and 2020 and created two cohorts.
The first cohort included 41,744 patients who were followed for up to 3 years for ATE/VTE after being given immune checkpoint inhibitors (n=7880), multikinase inhibitors (n=3394), CDK4/6 inhibitors (n=1966), or agents targeting VEGF (n=12,802), EGFR (n=8603), HER2 (n=11,683) or ALK/ROS1 (n=199). Of this targeted therapy cohort, 62.9% began their treatment within a year of diagnosis and 48.9% within 6 months.
The 3-year cumulative incidence of ATE was highest among those using immune checkpoint inhibitors, affecting 3.7% of patients, followed by those using multikinase inhibitors (3.4%), CDK4/6 inhibitors (2.6%), EGFR-targeted therapies (2.6%), ALK/ROS1-targeted therapies (2.5%), VEGF-targeted therapies (2.4%) and HER2-targeted therapies (1.4%).
For VTE, the 3-year cumulative incidence was highest among patients using therapies targeting EGFR, ALK/ROS or VEGF (9.3, 9.2 and 8.8%, respectively), followed by those given immune checkpoint inhibitors (8.1%), multikinase inhibitors (7.5%), CKD4/6 inhibitors (6.9%) and HER2-targeted agents (3.4%).
The second study cohort included 292,916 patients who were followed up after being diagnosed with breast (n=75,553), colorectal (n=67,959), lung (n=65,647), gynaecological (n=25,894), or urogenital cancer (n=25,083), or melanoma (n=32,780).
This revealed that the associations between the use of targeted therapies and ATE and VTE risk varied according to cancer type, Moik et al say.
For instance, there was no increased risk of ATE in breast cancer patients who used HER2- or CDK4/6-targeted agents versus no use, but there was an increased risk of VTE with these agents, despite the risk being low in this patient population generally (HR=1.38 and 1.78, respectively). Colorectal cancer patients using anti-VEGF and anti-EGFR agents versus no use had increased risks of both ATE (HR=1.25 and 1.38, respectively) and VTE (HR=2.31 and 2.47).
For lung cancer patients, use versus no use of anti-VEGF agents increased the risk of ATE and VTE (HR=1.57 and 1.58, respectively), with increased VTE risks also found with the use of immune checkpoint inhibitors and anti-EGFR agents (HR=1.23 and 2.26, respectively).
“Consistently, ALK/ROS-targeted therapy exposure was not associated with thromboembolic risk in our study”, the researchers observe.
Acknowledging the “scarce” data on the causes of thromboembolism with targeted therapies, the team advises that “future studies should focus on identifying risk factors and biomarkers for predicting thromboembolic events in patients receiving targeted cancer therapy.”
The investigators continue: “Furthermore, given the underreporting of thromboembolic events in clinical trials investigating targeted cancer therapies, consistent reporting of cardiovascular events should be prioritized.”
They say that “dedicated studies should focus on identifying potential mechanisms of cardiovascular toxicity in targeted cancer therapies.”
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eClin Med 2025; 87: 103440
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00372-4/fulltext
Keywords: venous thromboembolism, targeted therapies, immune checkpoint inhibitors, multikinase inhibitors, CDK4/6 inhibitors, ALK/ROS1 targeted therapies, VEGF-targeted therapies, HER2-targeted therapies