Abdel-Razeq Hikmat, Sharaf Baha', AlMasri Rama, Abdel-Razeq Rashid, Tamimi Faris, Khader Omar, Salama Osama, Abunasser Mahmoud, Edaily Sarah, Abdulelah Hazem
Department of Internal Medicine, King Hussein Cancer Center, Amman, Jordan.
Department of Internal Medicine, School of Medicine, The University of Jordan, Amman, Jordan.
Cancer Manag Res. 2022 Mar 8;14:1033-1041. doi: 10.2147/CMAR.S353584. eCollection 2022.
Cyclin dependent kinase (CDK) 4/6 inhibitors (palbociclib, ribociclib and abemaciclib) modulate endocrine resistance and are integral treatment for patients with advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Since their approval, CDK4/6 inhibitors are widely used in clinical practice. Thromboembolic events (TEE) were not a major issue in patients treated on clinical trials utilizing these agents. However, conflicting data started to emerge describing higher than expected rates of both arterial and venous thrombosis in patients treated with CDK4/6 inhibitors. In this study, we report our experience on TEE in patients treated with one of these agents (ribociclib) in real-world settings.
All consecutive patients with metastatic breast cancer (mBC) treated with ribociclib combined with letrozole or fulvestrant were retrospectively reviewed. All episodes of radiologically confirmed arterial or venous thrombosis were recorded. TEE was considered ribociclib-related if diagnosed while patients are on the drug, or within 4 weeks after the last dose.
A total of 305 patients, median age (range), 49 (22-87) years were enrolled. All patients had metastatic disease, and most (n=241, 79.0%) were with visceral metastasis. Ribociclib was used for a median duration of 7 months (range: 1-45) and was used beyond the first-line setting in 110 (35.9%) patients. TEE were confirmed on 6 (1.97%) patients; 3 were pulmonary embolism, 2 cerebral venous sinus thrombosis (CVST), and one case of limb ischemia and all were symptomatic. Similar rates of TEE were noted prior to initiation, and after stopping ribociclib.
In real-world settings, breast cancer patients treated with ribociclib, combined with aromatase inhibitors or fulvestrant, may not be at higher risk for thromboembolic events. However, unusual sites of thrombosis, like CVST, may raise some concerns.
细胞周期蛋白依赖性激酶（CDK）4/6抑制剂（帕博西尼、瑞博西尼和阿贝西利）可调节内分泌耐药性，是晚期激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性乳腺癌患者的重要治疗手段。自获批以来，CDK4/6抑制剂在临床实践中得到广泛应用。在使用这些药物进行临床试验的患者中，血栓栓塞事件（TEE）并非主要问题。然而，出现了相互矛盾的数据，描述了使用CDK4/6抑制剂治疗的患者中动脉和静脉血栓形成率高于预期。在本研究中，我们报告了在现实环境中使用其中一种药物（瑞博西尼）治疗的患者发生TEE的经验。
对所有接受瑞博西尼联合来曲唑或氟维司群治疗的转移性乳腺癌（mBC）连续患者进行回顾性研究。记录所有经影像学证实的动脉或静脉血栓形成事件。如果在患者用药期间或最后一剂后4周内确诊TEE，则认为与瑞博西尼相关。
共纳入305例患者，中位年龄（范围）为49（22 - 87）岁。所有患者均有转移性疾病，大多数（n = 241，79.0%）有内脏转移。瑞博西尼的中位使用时间为7个月（范围：1 - 45），110例（35.9%）患者在一线治疗后仍继续使用。6例（1.97%）患者确诊为TEE；3例为肺栓塞，2例为脑静脉窦血栓形成（CVST），1例为肢体缺血，所有病例均有症状。在开始使用瑞博西尼之前和停止使用瑞博西尼之后，TEE的发生率相似。
在现实环境中，接受瑞博西尼联合芳香化酶抑制剂或氟维司群治疗的乳腺癌患者发生血栓栓塞事件的风险可能并不更高。然而，血栓形成的不寻常部位，如CVST，可能会引起一些关注。
