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.

Abstract

PURPOSE:

Approximately 70% of patients with metastatic breast cancer (MBC) are hormone receptor (HR)-positive. Recent studies have shown that CDK4/6 inhibitors (CDKI) improve survival in combination with ET in HR-positive, HER2-negative MBC. The risk of venous thromboembolism (VTE) is 3-4 times higher in patients with breast cancer (BC) than in patients without cancer. The risk is even higher in BC patients receiving ET and chemotherapy. The aim of the study was to determine the VTE risk of CDKIs plus ET versus ET alone in patients with HR-positive, HER2-negative MBC.

METHODS:

We performed a systematic review and meta-analysis to demonstrate the risk of VTE in patients with HR-positive HER2-negative MBC treated with combined CDKIs and ET versus ET alone.

RESULTS:

Eight randomized controlled trials (RCT) with a total of 4,557 patients were eligible. The study arms comprised of palbociclib or ribociclib or abemaciclib plus ET while the control arms utilized placebo plus ET. The VTE events were 56 (2%) in the CDKIs plus ET group compared to 10 (0.5%) in the control group. Pooled relative risk (RR) for VTE was 2.62 (95% CI 1.21-5.65; P = 0.01) and the risk difference (RD) was 0.01 (95% CI 0.00-0.03; P = 0.02). Over a median follow-up of up to 36 months, RR was 3.18 (95% CI 1.22-8.24; P = 0.02) and RD was 0.03 (95% CI 0.01-0.06, P = 0.008).

CONCLUSIONS:

Our meta-analyses demonstrated that the addition of CDKIs to ET in patients with HR-positive HER 2-negative MBC contribute to a higher incidence of VTE. Further trials are required to define the actual relation and definitive incidence of VTE with different CDKIs.

• Authors: Kyaw Zin Thein, Thura Win Htut, Somedeb Ball, Sriman Swarup, Anita Sultan, Thein Hlaing Oo
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 183 Issue 2 Pg. 479-487 (Sep 2020) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 32647939 (Publication Type: Comparative Study, Journal Article, Meta-Analysis, Systematic Review)

Chemical References

• Antineoplastic Agents, Hormonal
• ESR1 protein, human
• Estrogen Receptor alpha
• Protein Kinase Inhibitors
• Receptors, Progesterone
• ERBB2 protein, human
• Receptor, ErbB-2
• CDK4 protein, human
• CDK6 protein, human
• Cyclin-Dependent Kinase 4
• Cyclin-Dependent Kinase 6

Topics

• Antineoplastic Agents, Hormonal (adverse effects)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cyclin-Dependent Kinase 4 (antagonists & inhibitors)
• Cyclin-Dependent Kinase 6 (antagonists & inhibitors)
• Drug Therapy, Combination
• Estrogen Receptor alpha (metabolism)
• Female
• Humans
• Neoplasm Metastasis
• Protein Kinase Inhibitors (adverse effects)
• Randomized Controlled Trials as Topic
• Receptor, ErbB-2 (metabolism)
• Receptors, Progesterone (metabolism)
• Risk Factors
• Venous Thromboembolism (chemically induced, pathology)