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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

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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.

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Authors and Affiliations

  1. Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA

    Kyaw Zin Thein

  2. Department of Hematology, Aberdeen Royal Infirmary Hospital, University of Aberdeen, Aberdeen, UK

    Thura Win Htut

  3. Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, USA

    Somedeb Ball

  4. Department of Hematology/Oncology, Texas Tech University Health Sciences Center, Lubbock, USA

    Sriman Swarup & Anita Sultan

  5. Section of Benign Hematology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd (Unit 1464), Houston, TX, 77030, USA

    Thein Hlaing Oo

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  1. Kyaw Zin Thein
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Kyaw Z. Thein, Thura W. Htut, Somedeb Ball, Sriman Swarup, and Anita Sultan declare no conflict of interest. Thein H. Oo received honoraria from Medical Education Speakers Network, served as a co-investigator for Janssen and Janssen and on Advisory Board for Bristol-Myers Squibb, not related to this manuscript.

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Thein, K.Z., Htut, T.W., 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 183, 479–487 (2020). https://doi.org/10.1007/s10549-020-05783-3

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