PO67 | TARGETED THERAPIES FOR CANCER AND THE RISK OF ARTERIAL AND VENOUS THROMBOEMBOLISM

O. Iqbal | Loyola University Stritch School of Medicine, Maywood, IL, USA

Aim. The therapeutic landscape of novel antineoplastic therapies is ever changing. With the advent of antibody-drug conjugates (ADCs), there is increased life expectancy and hope for a cure but also adverse events, including arterial thromboembolism (ATE) and venous thromboembolism (VTE). Other anti-cancer agents also cause cardiotoxic effects that led to the burgeoning field of oncocardiology.

Materials and Methods. The association of ATE and VTE due to ADCs is based on the literature searches performed in PubMed.

Results. As of January 2026, the FDA has approved approximately 15 to 20 ADCs as targeted therapies for cancer. Inotuzumab ozogamicin (Besponsa) showed the strongest signal for an increased risk of VTE. While several ADCs, including enfortumab vedotin (Padcev), brentuximab vedotin (Adcetris), polatuzumab vedotin (Polivy), and tizotumab vedotin (Tivdak), have less association with a risk for ATE. It is crucial to understand the mechanism of development of VTE or ATE due to ADCs. It is reported that tissue factor (TF) is expressed in tumor cells and tumor vasculature in many solid tumors, including cervical, bladder, and prostate cancer. TF is known to complex with factor VIIa and induce clot formation. TF can trigger intracellular signaling and, through protease-activated receptor two, can produce proangiogenic factors, cytokines, and adhesion molecules, causing tumor growth, angiogenesis, and metastasis. Given that interference with TF in tumors causes inhibition of tumor growth and overexpression of TF causes poor prognosis, it has promoted the development of the first TF-targeting ADCs, such as XB002, in advanced solid tumors, but it was later discontinued. The existing TF-targeting ADC, tisotumab vedotin, approved as a second-line treatment for recurrent or metastatic cervical cancer, is associated with an increased risk of bleeding requiring immediate attention or discontinuation of the drug. Besides ADCs, other anticancer agents such as anti-angiogenesis inhibitors like bevacizumab are associated with an increased risk of ATE; abemaciclib, while a CDK4/6 inhibitor, carries a risk of VTE. Balantamab mefudotin may also cause ocular manifestations, including keratitis and corneal microcysts.

Conclusions. This presentation will discuss various ADCs and the associated risk of arterial and VTE.