Department of Pharmacy, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
The School of Automation Science and Electrical Engineering, 12633Beihang University, Beijing, China.
Int J Immunopathol Pharmacol. 2022 Jan-Dec;36:3946320221145520. doi: 10.1177/03946320221145520.
The haematopoietic cytopenia (HC) of the cyclin-dependent kinase (CDK)4/6 inhibitors was evaluated using the Food and Drug Administration Adverse Event Reporting System (FAERS).
Data from 1 January 2015 to 31 December 2021 has been retrieved from the FAERS database. Disproportionality analysis and Bayesian analysis were utilized in the data mining. The reporting odds ratio (ROR) with 95% confidence interval (CI) for HC was calculated for each CDK 4/6 inhibitor agent. Clinical features of the patients were collected and compared between death outcome and non-death outcome groups. Time to onset (TTO), proportion of deaths, life-threatening and hospitalizations of CDK 4/6 inhibitors-associated HC were also studied.
A total of 17,235 cases of HC associated with CDK 4/6 inhibitors were identified with a median age of 65 years (interquartile range [IQR] 57-73). Palbociclib appeared the strongest signal, with the highest (ROR 9.64, 95% CI 9.46-9.83), followed by ribociclib (ROR 6.38, 95% CI 6.04-6.73) and then abemaciclib (ROR 2.72, 95% CI 2.49-2.97). Patients aged 18-64 had a higher proportion of deaths than those aged 65-84 (12.21% vs. 9.91%, = 0.001). In Africa and Asia, the proportions of deaths were higher (31.65% and 26.13%, respectively). The median TTO was 26 days (IQR 14-65) for abemaciclib, 33 days (IQR 15-134) for palbociclib and 23 days (IQR 14-69) for ribociclib, respectively. The highest proportion of deaths, life-threatening and hospitalizations all occurred in abemaciclib (13.00%, 5.42% and 44.04%, respectively).
Greater proportions of deaths occurred in Africa and Asia. HC may occur early in any CDK 4/6 inhibitor regimen. Abemaciclib had the highest proportion of deaths, life-threatening and hospitalizations. Health care workers should be more concerned about CDK 4/6 inhibitors. The higher proportions of serious events, including deaths, from Africa and Asia, as well as for abemaciclib, deserve further investigations through additional pharmacoepidemiological approaches.
利用食品和药物管理局不良事件报告系统（FAERS）评估细胞周期蛋白依赖性激酶（CDK）4/6 抑制剂引起的血液学细胞减少症（HC）。
从 FAERS 数据库中检索了 2015 年 1 月 1 日至 2021 年 12 月 31 日的数据。使用不稳定性分析和贝叶斯分析进行数据挖掘。计算了每种 CDK 4/6 抑制剂的 HC 报告比值比（ROR）及其 95%置信区间（CI）。收集患者的临床特征，并在死亡结局和非死亡结局组之间进行比较。还研究了 CDK 4/6 抑制剂相关 HC 的发病时间（TTO）、死亡率、危及生命和住院率。
共发现 17235 例与 CDK 4/6 抑制剂相关的 HC，中位年龄为 65 岁（四分位距 [IQR] 57-73）。哌柏西利表现出最强的信号，其 ROR 最高（9.64，95%CI 9.46-9.83），其次是瑞波西利（ROR 6.38，95%CI 6.04-6.73），然后是阿贝西利（ROR 2.72，95%CI 2.49-2.97）。18-64 岁患者的死亡率高于 65-84 岁患者（12.21%比 9.91%，=0.001）。在非洲和亚洲，死亡率的比例较高（分别为 31.65%和 26.13%）。阿贝西利的中位 TTO 为 26 天（IQR 14-65），哌柏西利为 33 天（IQR 15-134），瑞波西利为 23 天（IQR 14-69）。阿贝西利的死亡率、危及生命和住院率最高（分别为 13.00%、5.42%和 44.04%）。
非洲和亚洲的死亡率比例更高。任何 CDK 4/6 抑制剂方案中均可能较早出现 HC。阿贝西利的死亡率、危及生命和住院率最高。卫生保健工作者应更加关注 CDK 4/6 抑制剂。非洲和亚洲的严重事件（包括死亡）的比例更高，阿贝西利的比例也更高，这值得通过额外的药物流行病学方法进行进一步调查。
