Raschi Emanuel, Fusaroli Michele, Ardizzoni Andrea, Poluzzi Elisabetta, De Ponti Fabrizio
Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy.
Medical Oncology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy.
Cancers (Basel). 2021 Apr 7;13(8):1758. doi: 10.3390/cancers13081758.
We analyzed thromboembolic events, recognized (AESIs), with cyclin-dependent kinase (CDK)4/6 inhibitors, using the Food and Drug Administration adverse event reporting system.
Thromboembolic events were characterized in terms of spectrum [venous and arterial thromboembolism (VTE; ATE)] and clinical features by combining the disproportionality approach [reporting odds ratio (ROR) with 95% confidence interval (CI)] with individual case assessment.
A total of 1722 thromboembolic events were retained. Increased VTE reporting emerged for CDK4/6 inhibitors in the exploratory analyses ( = 659; ROR = 1.51; 95% CI = 1.39-1.63), with consistent disproportionality in the consolidated analyses (e.g., deep vein thrombosis with abemaciclib: 17; 1.98; 1.22-3.19). Higher-than-expected ATE reporting was found for ribociclib, including myocardial infarction (41; 1.82; 1.33-2.48), with rapid onset (median latency 1 vs. 6 months for other CDK4/6 inhibitors). Causality was highly probable or probable in 83.2% of cases, with a negligible proportion of pre-existing drug- and patient-related risk factors except for cardiovascular comorbidities (26%).
Although causal association cannot be firmly inferred, oncologists should proactively monitor the occurrence of VTE with CDK4/6 inhibitors. The unexpected distinctive increased ATE reporting with ribociclib deserves urgent clarification though large comparative population-based studies. We support pharmacovigilance for the post-marketing characterization of AESIs, thus promoting real-time safe prescribing in oncology.
我们使用美国食品药品监督管理局不良事件报告系统分析了细胞周期蛋白依赖性激酶（CDK）4/6抑制剂相关的血栓栓塞事件及已确认的严重不良事件（AESIs）。
通过将不成比例分析方法[报告比值比（ROR）及95%置信区间（CI）]与个体病例评估相结合，对血栓栓塞事件的范围[静脉和动脉血栓栓塞（VTE；ATE）]及临床特征进行了描述。
共保留了1722例血栓栓塞事件。在探索性分析中，CDK4/6抑制剂的VTE报告有所增加（n = 659；ROR = 1.51；95% CI = 1.39 - 1.63），在综合分析中也存在一致的不成比例情况（例如，阿贝西利导致的深静脉血栓形成：17例；1.98；1.22 - 3.19）。发现瑞博西尼的ATE报告高于预期，包括心肌梗死（41例；1.82；1.33 - 2.48），且发病迅速（中位潜伏期为1个月，而其他CDK4/6抑制剂为6个月）。83.2%的病例因果关系很可能或可能存在，除心血管合并症（26%）外，既往药物和患者相关风险因素的比例可忽略不计。
尽管不能确凿推断因果关联，但肿瘤学家应积极监测CDK4/6抑制剂相关VTE的发生情况。瑞博西尼意外的独特的ATE报告增加情况，尽管需要基于大量比较人群的研究，但仍值得紧急澄清。我们支持对AESIs进行上市后特征的药物警戒，从而促进肿瘤学中的实时安全处方。
