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.

Related Items
Olaparib Extends Disease-Free Survival in Patients with Early-Stage Breast Cancer and BRCA Mutation
William King
TOP - November 2021 Vol 14, No 7 published on November 10, 2021 in Breast Cancer
Tucatinib plus Trastuzumab and Capecitabine Triplet Maintains Survival Benefit in HER2-Positive Metastatic Breast Cancer: Updated Results from HER2CLIMB Trial
Charlie Dawson
TOP - September 2021 Vol 14, No 5 published on September 7, 2021 in Breast Cancer
Cryoablation Appears Safe and Effective in Low-Risk, Early-Stage Breast Cancer
William Ackerman
TOP - July 2021 Vol 14, No 4 published on July 20, 2021 in Breast Cancer
Pembrolizumab plus Chemotherapy Improves Progression-Free Survival in Metastatic TNBC
Patricia Stewart
TOP - May 2021 Vol 14, No 3 published on May 14, 2021 in Breast Cancer
Abemaciclib plus Endocrine Therapy Offers Invasive Disease–Free Survival Benefit in Patients with High-Risk, HR-Positive, Early-Stage Breast Cancer
Patricia Stewart
TOP - May 2021 Vol 14, No 3 published on May 14, 2021 in Breast Cancer
Breast Cancer Year in Review Introduction
2020 Year in Review - Breast Cancer published on January 24, 2021 in Breast Cancer
Retrospective Analysis Provides Insight into Treatment-Emergent Neutropenia Among Patients with Metastatic Breast Cancer Treated with Ribociclib or Palbociclib
2020 Year in Review - Breast Cancer published on January 24, 2021 in Breast Cancer
Concurrent Use of Medications with Potential Drug–Drug Interactions: Real-World Analysis of Patients Treated with CDK4/6 Inhibitors
2020 Year in Review - Breast Cancer published on January 24, 2021 in Breast Cancer
Abemaciclib plus Fulvestrant Provides Statistically Significant Benefit as First- and Second-Line Therapy for Hormone Receptor–Positive, HER2-Negative Advanced Breast Cancer
2020 Year in Review - Breast Cancer published on January 24, 2021 in Breast Cancer
Preliminary Results from a Phase 2 Trial of Fulvestrant/Palbociclib as First-Line Therapy in Postmenopausal Women with Hormone Receptor–Positive, HER2-Negative Endocrine-Sensitive Advanced Breast Cancer
2020 Year in Review - Breast Cancer published on January 24, 2021 in Breast Cancer
Last modified: July 22, 2021