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

Nada Alsuhebany,1– 3 Ahmed Alanazi,4 Mohammed Y Alzahrani,1– 3 Saleh Alyousef,1 Bandar S Aldawish,1 Sultan Aljardan,1 Rawan Abu Alnasr,4 Ibtihal Mohammed Althumali,4 Maha AlDoughaim,1– 3 Lama Alfehaid,1– 3 Sadal Refae,2,5 Nafisa Abbas Abdelhafiez Jnr,2,5 Hatoon Bakhribah,6 Tariq Alqahtani1,2 1Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 2King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 3Department of Pharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia; 4Pharmacy Service Administration, King Fahad Medical City, Riyadh, Saudi Arabia; 5Division of Adult Medical Oncology, Department of Oncology, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia; 6Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi ArabiaCorrespondence: Nada Alsuhebany, Department of Clinical Pharmacy, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, 2915 Al Haras Al Watani St, Ar Rimayah, Riyadh, 14611, Saudi Arabia, Tel +966500828585, Email nalsuhebany@gmail.comIntroduction: 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.Keywords: thrombotic risk, venous thromboembolism, CDK4/6 inhibitors, breast cancer, hormone receptor-positive, real-world data, thrombosis risk assessment, deep vein thrombosis, DVT, pulmonary embolism, PE