Incidence of Thrombotic Events with CDK4/6 Inhibitor Use in Real-World Practice Compared with Clinical Trial Settings

2020 Year in Review - Breast Cancer - Breast Cancer

Thrombotic event incidence was higher in this real-world study than that which was reported in clinical trials, with arterial thrombosis accounting for more than one-third of events.

Combined with endocrine therapy, CDK4/6 inhibitors play a key role in the treatment of hormone receptor–positive advanced breast cancer.

In the clinical trials leading to approval of the CDK4/6 inhibitor abemaciclib, venous thromboembolic events occurred at a rate of 1% to 5%. Therefore, a warning was issued regarding venous thromboembolic events risk for abemaciclib.

Because real-world experience helps to depict a more accurate picture of thrombosis risk, Malinda West, MD, First Year Fellow, Hematology and Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, and colleagues used real clinical experience at the Knight Cancer Institute and affiliated clinics between February 2015 and March 2020 to investigate the thrombotic risk associated with CDK4/6 inhibitors, also including an evaluation of arterial and venous events.

To help elucidate what predisposing variables increased the risk for thrombotic events, the research team investigated whether there were predictors of which patients receiving CDK4/6 inhibitors had thrombosis, and whether these could be predicted.

A retrospective analysis of patients with breast cancer was used, and patients who had been prescribed therapy with a CDK4/6 inhibitor (abemaciclib, palbociclib, or ribociclib) were included in the study. Patients were included if arterial or venous thrombosis occurred during treatment or within 30 days of discontinuation.

Included in the study were 270 patients, of which 10.7% (N = 29) had a thrombotic event. Two-thirds of these events were venous, while 10% had more than 1 clot, and 28% had arterial events. The thrombotic events occurred at a rate of 5% with abemaciclib therapy, 9% with palbociclib therapy, and 17% with ribociclib therapy.

Statistically significant predictors of thrombosis were not found based on an evaluation of risk factors for thrombosis. Furthermore, Khorana scores were unable to predict which patients would have a thrombotic event. When comparing those who developed thrombosis and those who did not, median OS did not significantly differ (23 months vs 17.5 months, respectively; P = .37).

Thrombotic event incidence was higher in this study than that which was reported in clinical trials. Accounting for more than one-third of events was arterial thrombosis. The investigators suggested that there may be a class effect. Large-scale, real-world studies will help clarify whether there is CDK4/6 inhibitor–induced increased risk for thrombosis. Clarifying if there is a role for prophylactic anticoagulation remains to be defined.

Source: West M, Smith C, Kohs T, et al. CDK 4/6 inhibitors are associated with a high incidence of thrombotic events in real world practice. Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PS13-24.

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Last modified: July 22, 2021