Thrombotic events in patients using cyclin dependent kinase 4/6 inhibitors, analysis of existing ambulatory risk assessment models and the potential influences of tumor specific risk factors.

Cyclin dependent kinase 4 of 6 inhibitors (CDKi) are key therapeutics in the treatment of advanced breast cancer and have recently been approved in small cell lung cancer for the prevention of myelosuppression. Thrombotic events have emerged as a significant treatment related adverse event in up to 5% of patients in clinical trials and has been reported at higher rates, up to 10%, in real world analysis. The prothrombotic mechanisms of CDKis, however, remain unknown. Cancer specific risk assessment models exist to identify who may be at highest risk of thrombosis and who could potentially benefit from prophylactic anticoagulation. However, these models may not be accurate in patients taking CDKis and may not fully capture recently identified thrombotic risk factors such as tumor specific somatic mutations. In the following manuscript, we summarize the literature on thrombotic events with CDKis in clinical trials and real-world settings, review the existing thrombosis risk assessment models for ambulatory cancer patients, and discuss the literature on tumor mutations and role in cancer associated thrombosis.