最近，细胞周期蛋白依赖性激酶 4/6 抑制剂 (CDK4/6i) 已成为乳腺癌的一种新型治疗策略。然而，越来越多的 CDK4/6i 相关静脉血栓栓塞 (VTE) 的报道引起了人们的关注。本研究评估了乳腺癌中CDK4/6i相关的VTE，并首次在体外检验了CDK4/6i对血小板/凝血功能的影响。检索PubMed和Embase数据库，查找建库至12月发表的研究2022年12月31日进行了乳腺癌患者CDK4/6i的随机对照试验（RCT）和真实世界研究，从纳入的研究中获得的数据用于荟萃分析。还通过从 FDA 不良事件报告系统 (FAERS) 数据库中提取 CDK4/6i 相关 VTE 的药物不良反应信号进行了不成比例分析。此外，基于血小板聚集试验和流式细胞术评估CDK4/6i对血小板功能的体外影响，并基于凝血功能测试评估凝血功能。 13项RCT共纳入16,903名患者，9项随机对照试验共纳入6,490名患者。荟萃分析中纳入了现实世界的研究。在 RCT 中，CDK4/6i 组和对照组分别有 193 名 (2.1%) 和 55 名 (0.7%) 患者发生 VTE。在现实世界的研究中，VTE 的总发病率为 4.2%（95% CI：2.1，6.3）。 RCT 的荟萃分析显示，abemaciclib（优势比 [OR]：4.40 [95% CI：2.74,7.05]，p < 0.001）和 Palbociclib（OR：2.35 [95% CI：1.34, 4.12]，p < 0.01 ）与安慰剂相比，乳腺癌患者发生 VTE 的风险显着增加。 FAERS 数据库分析显示，abemaciclib（报告优势比 [ROR]：1.63 [95% CI：1.36, 1.97]；IC025：0.67）和 ribociclib（ROR：1.17 [95% CI：1.0，1.39]；IC025：0.18）证明VTE 信号显着增强。同样，体外实验结果表明，abemaciclib 增强激动剂诱导的血小板活化，特别是当胶原蛋白作为诱导剂时，这种作用随着其浓度的增加而变得更加明显。 使用 abemaciclib 可能会增加乳腺癌患者发生 VTE 的风险癌症，这可能部分归因于 abemaciclib 对血小板功能的影响。强烈建议在使用 abemaciclib 时密切监测 VTE 的发生，特别是对于 VTE 高风险的患者。版权所有 © 2024 Elsevier Ltd。保留所有权利。

Recently, cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have emerged as a novel treatment strategy for breast cancer. However, increasing reports of CDK4/6i-associated venous thromboembolism (VTE) have garnered attention. This study assessed CDK4/6i-associated VTE in breast cancer, and examined the effect of CDK4/6i on platelet/coagulation function for the first time in vitro.PubMed and Embase databases were searched for studies published from the establishment of the database to December 31, 2022 for randomized controlled trials (RCTs) and real-world studies of CDK4/6i in patients with breast cancer, and the data obtained from the included studies were used for meta-analysis. A disproportionality analysis by extracting adverse drug reaction signals of CDK4/6i-associated VTE from the FDA Adverse Event Reporting System (FAERS) database was also conducted. Additionally, the in vitro effect of CDK4/6i on platelet function was assessed based on platelet aggregation tests and flow cytometry, and coagulation function was assessed based on the blood clotting function test.A total of 16,903 patients in 13 RCTs and 6,490 patients in 9 real-world studies were included in the meta-analysis. In RCTs, VTE occurred in 193 (2.1 %) and 55 (0.7 %) patients in the CDK4/6i and control groups, respectively. In real-world studies, the aggregate incidence rate of VTE was 4.2 % (95 % CI: 2.1, 6.3). The meta-analysis of RCTs revealed that abemaciclib (Odds ratio [OR]: 4.40 [95 % CI: 2.74,7.05], p < 0.001) and palbociclib (OR: 2.35 [95 % CI: 1.34, 4.12], p < 0.01) significantly increased the risk of VTE in patients with breast cancer compared to placebo. FAERS database analysis revealed that abemaciclib (reporting odds ratio [ROR]: 1.63 [95 % CI: 1.36, 1.97]; IC025: 0.67) and ribociclib (ROR: 1.17 [95 % CI: 1.0, 1.39]; IC025: 0.18) demonstrated a significantly increased signal of VTE. Similarly, findings from in vitro experiments demonstrated that abemaciclib enhanced agonist-induced platelet activation, especially when collagen was used as the inducer, and this effect became more prominent with increasing its concentration.Use of abemaciclib may increase the risk of VTE in patients with breast cancer, which may be partially attributed to the effect of abemaciclib on platelet function. Close monitoring of VTE occurrence is highly recommended while using abemaciclib, especially in patients at a high risk of VTE.Copyright © 2024 Elsevier Ltd. All rights reserved.