Real-World Analysis of Thromboembolic Events in Patients Treated with Ribociclib with Letrozole or Fulvestrant for Hormone Receptor–Positive, HER2-Negative Metastatic Breast Cancer

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Endocrine therapy is the preferred first-line treatment for patients with hormone receptor (HR)‐positive breast cancer, particularly for those with low burden disease. However, most patients with HR-positive metastatic breast cancer become resistant to endocrine therapy. As a modulator of endocrine therapy resistance, CDK4/6 inhibitors play an integral role in the treatment of patients with advanced HR-positive, HER2-negative breast cancer. In CDK4/6 clinical trials, thromboembolic events were not a major issue among treated patients. However, emerging data from clinical practice characterize higher than expected rates of arterial and venous thrombosis in patients treated with CDK4/6 inhibitors. Real-world data have been used to study thromboembolic event rates in patients treated with ribociclib in real-world clinical settings.

In this retrospective analysis of data collected from patients’ electronic medical records and radiology department archives, all patients with metastatic breast cancer treated with ribociclib combined with aromatase inhibitors or fulvestrant were reviewed. All radiology-confirmed arterial or venous thrombosis events were recorded. Ribociclib-related thromboembolic events were considered if a thromboembolic event was diagnosed while patients were actively treated or within 4 weeks after the last dose of ribociclib.

Enrollment in this study included 305 patients with a median age of 49 years (range, 22-87 years). All patients had metastatic disease and 55.1% were de novo metastatic. At the time of treatment with ribociclib, 79.0% of the patients had visceral metastasis and 20.9% had bone-only disease. Ribociclib was used in combination with letrozole in the first-line setting in 63.9% of patients and with fulvestrant or letrozole in 35.9% of patients who failed ≥1 lines of endocrine therapy or chemotherapy. Patients received treatment with ribociclib for a median duration of 7 months (range, 1-45 months). Venous thromboembolic events were confirmed in only 5 (1.6%) patients; 3 were pulmonary embolism with or without deep vein thrombosis and 2 were lower extremity deep vein thrombosis. All were symptomatic. Another patient had arterial thrombosis. Chart review revealed that 7 (2.3%) more patients had a confirmed diagnosis of venous thromboembolism prior to ribociclib therapy, and another 4 (1.3%) patients had a confirmed episode after (range, 2-7 months) stopping treatment with ribociclib. All patients were treated with low-molecular-weight heparin and experienced no complications. Given the small number of patients with thromboembolic events, no clinical or pathologic predictors could be used to identify subgroups of patients at higher risk for thromboembolic events while on ribociclib.

The investigators concluded that contrary to recent reports, in real-world settings breast cancer patients treated with ribociclib with an aromatase inhibitor or fulvestrant are not at increased risk for arterial or venous thromboembolic events. Patients had similar rates of thrombosis prior to treatment initiation, and after stopping ribociclib.


Hikmat Abdel-Razeq H, Tamimi F, Edaily S, et al. Thromboembolic events (TEE) in patients with HER2-negative, hormone receptor-positive metastatic breast cancer treated with ribociclib combined with letrozole or fulvestrant. Real-world data. 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021. P4-02-15.

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