Assessing Thrombotic Risk in Patients with HR+/HER2- Breast Cancer Receiving CDK4/6 Inhibitors: Insights from Real-World Data from the Middle East

Introduction: Hormone receptor-positive, HER2-negative (HR+/HER2-) is the most common subtype of breast cancer in women. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, such as palbociclib, ribociclib, and abemaciclib play an important role in the treatment of advanced HR+/HER2- breast cancer. However, CDK4/6 inhibitors might be associated with an increased risk of thrombotic events, including venous thromboembolism (VTE). Methods: We conducted a retrospective study at two centers in Saudi Arabia, analyzing data from 447 patients treated with CDK4/6 inhibitors for HR+/HER2- breast cancer between 2016 and 2023. Patients with early-stage, high-risk breast cancer receiving abemaciclib for at least one month were included. The primary outcomes were the incidence of VTE and arterial thrombosis. Results: A total of 505 patients were screened in which 447 breast cancer patients receiving CDK4/6 inhibitors were included. Majority of patients were on palbociclib (70.4%), followed by abemaciclib (28.8%), and then ribociclib (0.67%). The thrombotic events were 11.8% (n=53), with 37.7% of these being pulmonary embolism (PE) and 18.8% symptomatic deep vein thrombosis (DVT). Patients with a prior history of VTE had a significantly higher risk of thrombosis (p=0.03). Abemaciclib was associated with a higher incidence of thrombosis (16.3%), followed by palbociclib (10.2%), and none of the three patients on ribociclib developed thrombosis. The median time to develop thrombosis while receiving CDK4/6 inhibitor therapy was 11.8 months. There was no significant difference in overall survival in breast cancer patients who developed thrombosis compared to patients without thrombosis (p=0.55). Conclusion: This study shows a higher incidence of thrombotic events in real-world settings than clinical trials, emphasizing the need for risk assessment and possible thromboprophylaxis in patients receiving CDK4/6 inhibitors. Future risk assessment tools needed to be applied in breast cancer patients receiving CDK4/6 inhibitors and risk of developing thrombosis.