Summary Safety Review - Ibrance (palbociclib) - Assessing the Potential Risk of Venous Thromboembolism

Ibrance (palbociclib)

Venous thromboembolism (VTE), a condition where a blood clot forms in a vein blocking the flow of blood through parts of the body

• Health Canada’s safety review found a probable link between the use of Ibrance and the risk of VTE.

• Health Canada reviewed the potential risk of VTE with the use of Ibrance, a prescription drug belonging to a class of drugs called cyclin-dependent kinase inhibitors (CDKIs). It is authorized for the treatment of metastatic breast cancer in combination with certain prescription drugs. The safety review was triggered by a study published in 2020 suggesting that the risk of VTE may be a class effect associated with all CDKIs.

• Health Canada is working with the manufacturer to update the product safety information in the Canadian product monograph (CPM) for Ibrance to include the risk of VTE.

Health Canada reviewed the potential risk of VTE with the use of Ibrance. The safety review was triggered by the 2020 publication of a study that found a higher risk of VTE with the use of CDKIs, a class of drugs to which Ibrance belongs¹.

Venous thromboembolism, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a condition where a blood clot forms in a vein blocking the flow of blood through parts of the body. Deep vein thrombosis is a blood clot in a deep vein of the body, usually in the legs. A PE occurs when a DVT dislodges and travels to the lung artery, blocking blood flow and oxygen to the lungs. If not treated quickly, VTE can lead to disability and death.

At the time of the review, the CPMs for the other CDKIs, Verzenio (abemaciclib) and Kisqali (ribociclib), included warnings for the risk of VTE, but not the CPM for Ibrance.

• Ibrance is a prescription drug belonging to a class of drugs called CDKIs. It is authorized for sale in Canada for the treatment of metastatic breast cancer in combination with certain prescription drugs.

• Ibrance has been marketed in Canada since 2016. It is currently available as 75 mg, 100 mg and 125 mg tablets and capsules.

• Of the 3 CDKIs marketed in Canada, Ibrance is the most commonly used for breast cancer treatment. It is estimated that over 60,000 breast cancer patients may have been prescribed Ibrance since 2016.

• Health Canada reviewed information provided by the manufacturer and from the scientific literature.

• Health Canada reviewed 7 randomized controlled trials (RCTs) involving Ibrance, which included 8,793 patients. The majority (>95%) of these patients had early or metastatic breast cancer.

• Analysis of data across the 7 RCTs showed a higher risk of VTE with Ibrance treatment. Specifically, in the more relevant trials in metastatic breast cancer patients, VTE was reported in 3.4% of patients treated with Ibrance plus an endocrine therapy (medicine that either blocks the effects or interferes with the production of estrogen in the body), compared with 1.9% of patients treated with the endocrine therapy alone.

• The evidence reviewed supports a probable link between the risk of VTE and the use of Ibrance. This finding is consistent with the VTE findings for the other CDKIs marketed in Canada.

• Health Canada’s review of the available information concluded that there is a probable link between the use of Ibrance and the risk of VTE.

• Health Canada is working with the manufacturer to update the CPM for Ibrance to include the risk of VTE.

• Health Canada encourages patients and healthcare professionals to report any side effects related to the use of Ibrance, and other health products, to the Canada Vigilance Program.

• Health Canada will continue to monitor safety information involving Ibrance, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified.

The analysis that contributed to this safety review included scientific literature.

For additional information, contact the Marketed Health Products Directorate.

1. Thein KZ, Htut TW, Ball S, et al. Venous thromboembolism risk in patients with hormone receptor-positive HER2-negative metastatic breast cancer treated with combined CDK 4/6 inhibitors plus endocrine therapy versus endocrine therapy alone: a systematic review and meta-analysis of randomized controlled trials. Breast Cancer Res Treat. 2020 Sep;183(2):479-487.