Gervaso Lorenzo, Montero Alberto J, Jia Xuefei, Khorana Alok A
Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio.
J Thromb Haemost. 2020 Jan;18(1):162-168. doi: 10.1111/jth.14630. Epub 2019 Sep 18.
Venous thromboembolism (VTE) complicates several anticancer regimens including chemotherapy and antiangiogenic agents. Cyclin-dependent kinase inhibitors (CDKIs) are a new approach for hormone receptor-positive metastatic breast cancer (mBC). Reported VTE rates in randomized trials range from 0.6% to 5%, but these may underestimate actual rates observed in clinical practice.
Evaluate VTE rate and its association with outcomes in CDKIs patients.
PATIENTS/METHODS: We conducted a retrospective cohort study of consecutive mBC patients who received any of three Food and Drug Administration (FDA)-approved CDKIs (palbociclib, ribociclib, abemaciclib) from January 2015 through December 2017. Venous thromboembolism including deep venous thrombosis (DVT), pulmonary embolism (PE), and visceral vein thrombosis (VVT) were identified by electronic medical record review. Overall survival (OS) and progression-free survival (PFS) were estimated and evaluated for association with VTE using Cox proportional hazard regression.
We included 424 patients, with a median age at diagnosis of 55 years. Palbociclib was the most commonly used CDKI (n = 390, 91.8%). Venous thromboembolism during CDKIs occurred in 38 patients, 6.3% at year 1, including DVT in 52.6%, PE in 18.5%, and VVT in 15.8%. Median time to VTE was 314 days. Venous thromboembolism was associated with a trend to worse PFS and OS in multivariate analysis [PFS hazard ratio (HR) 1.40, 95% confidence interval (CI) 0.83-2.38, P = .21], OS (HR 1.70, 95% CI 0.95-2.98, P = .076).
Venous thromboembolism rates with CDKI treatment in mBC in clinical practice are 2-fold to 5-fold greater than reported in registration trials and may be associated with worse outcomes.
静脉血栓栓塞症（VTE）使包括化疗和抗血管生成药物在内的多种抗癌方案变得复杂。细胞周期蛋白依赖性激酶抑制剂（CDKIs）是治疗激素受体阳性转移性乳腺癌（mBC）的一种新方法。随机试验中报告的VTE发生率在0.6%至5%之间，但这些可能低估了临床实践中观察到的实际发生率。
评估CDKIs治疗患者的VTE发生率及其与预后的关系。
患者/方法：我们对2015年1月至2017年12月期间接受美国食品药品监督管理局（FDA）批准的三种CDKIs（哌柏西利、瑞博西尼、阿贝西利）中任何一种治疗的连续性mBC患者进行了一项回顾性队列研究。通过电子病历审查确定包括深静脉血栓形成（DVT）、肺栓塞（PE）和内脏静脉血栓形成（VVT）在内的静脉血栓栓塞症。使用Cox比例风险回归估计并评估总生存期（OS）和无进展生存期（PFS）与VTE的相关性。
我们纳入了424例患者，诊断时的中位年龄为55岁。哌柏西利是最常用的CDKI（n = 390，91.8%）。接受CDKIs治疗期间发生静脉血栓栓塞症的有38例患者，第1年的发生率为6.3%，其中DVT占52.6%，PE占18.5%，VVT占15.8%。VTE的中位发生时间为314天。在多变量分析中，静脉血栓栓塞症与PFS和OS变差的趋势相关[PFS风险比（HR）1.40，95%置信区间（CI）0.83 - 2.38，P = 0.21]，OS（HR 1.70，95% CI 0.95 - 2.98，P = 0.076）。
在临床实践中，mBC患者接受CDKI治疗的静脉血栓栓塞症发生率比注册试验中报告的高2至5倍，并且可能与更差的预后相关。
