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Abstract：
BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors marked a milestone in the breast cancer treatment. Due to the potential impact of adverse effects on treatment decisions and patient outcomes, careful consideration of the varying toxicities of CDK4/6 inhibitors is crucial, as three inhibitors-palbociclib, abemaciclib, and ribociclib-have been approved with differences in adverse event profiles. However, limitations in clinical trials call for urgent real-world safety studies to evaluate and compare the risk of adverse events (AEs) among these CDK4/6 inhibitors. Therefore, this study aimed to analyze AEs of CDK4/6 inhibitors and provide insights for clinical drug selection, using real world database.
METHODS: The AEs of CDK4/6 inhibitors in the FDA Adverse Event Reporting System (2015-2022) were analyzed. Four disproportionality methods were used to detect safety signals: reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Neural Network Propagation, and Multi-Item Gamma Poisson Shrinker. Venn analysis was used to compare and select common and specific AEs.
RESULTS: This study included 73,042 patients treated with palbociclib, 25,142 with ribociclib, and 7563 with abemaciclib. All three inhibitors had 27 common AEs. Palbociclib exhibited the highest ROR for hematologic toxicities, while ribociclib showed the highest ROR for macrocytosis, nail disorders, and hepatic lesions. Abemaciclib displayed the highest ROR for mucosal toxicity. Common signals for both palbociclib and ribociclib included hematologic toxicities, decreased immune responsiveness, and aphthous ulcers. Myelosuppression, oral pain, and pseudocirrhosis were common signals for palbociclib and abemaciclib. Anemia, hepatotoxicity, and pneumonitis were observed as common signals for ribociclib and abemaciclib. Furthermore, specific AEs associated with palbociclib included fatigue, alopecia, and stomatitis. For ribociclib, specific AEs included electrocardiogram QT prolongation, thrombocytopenia, and decreased hemoglobin. Abemaciclib was specifically linked to diarrhea, vomiting, and interstitial lung disease.
CONCLUSIONS: Our analysis revealed that palbociclib showed a higher risk of hematologic toxicity. Ribociclib showed higher risks of hepatotoxicity, nephrotoxicity, and QT prolongation. Abemaciclib showed higher risks of hepatotoxicity, gastrointestinal effects, interstitial lung disease, and thrombosis. These findings provide valuable insights for CDK4/6 inhibitor selection.
METHODS: The AEs of CDK4/6 inhibitors in the FDA Adverse Event Reporting System (2015-2022) were analyzed. Four disproportionality methods were used to detect safety signals: reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Neural Network Propagation, and Multi-Item Gamma Poisson Shrinker. Venn analysis was used to compare and select common and specific AEs.
RESULTS: This study included 73,042 patients treated with palbociclib, 25,142 with ribociclib, and 7563 with abemaciclib. All three inhibitors had 27 common AEs. Palbociclib exhibited the highest ROR for hematologic toxicities, while ribociclib showed the highest ROR for macrocytosis, nail disorders, and hepatic lesions. Abemaciclib displayed the highest ROR for mucosal toxicity. Common signals for both palbociclib and ribociclib included hematologic toxicities, decreased immune responsiveness, and aphthous ulcers. Myelosuppression, oral pain, and pseudocirrhosis were common signals for palbociclib and abemaciclib. Anemia, hepatotoxicity, and pneumonitis were observed as common signals for ribociclib and abemaciclib. Furthermore, specific AEs associated with palbociclib included fatigue, alopecia, and stomatitis. For ribociclib, specific AEs included electrocardiogram QT prolongation, thrombocytopenia, and decreased hemoglobin. Abemaciclib was specifically linked to diarrhea, vomiting, and interstitial lung disease.
CONCLUSIONS: Our analysis revealed that palbociclib showed a higher risk of hematologic toxicity. Ribociclib showed higher risks of hepatotoxicity, nephrotoxicity, and QT prolongation. Abemaciclib showed higher risks of hepatotoxicity, gastrointestinal effects, interstitial lung disease, and thrombosis. These findings provide valuable insights for CDK4/6 inhibitor selection.
摘要：
背景：细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂标志着乳腺癌治疗的一个里程碑。由于不良反应对治疗决策和患者预后的潜在影响，仔细考虑CDK4/6抑制剂的不同毒性是至关重要的，作为三种抑制剂-palbociclib，abemaciclib,和ribociclib-已被批准在不良事件概况方面存在差异。然而,临床试验的局限性需要紧急的真实世界安全性研究来评估和比较这些CDK4/6抑制剂的不良事件(AE)风险.因此,本研究旨在分析CDK4/6抑制剂的不良事件，为临床药物选择提供见解，使用真实世界的数据库。
方法：分析FDA不良事件报告系统（2015-2022）中CDK4/6抑制剂的不良事件。使用四种不成比例的方法来检测安全性信号：报告优势比(ROR)，比例报告比率，贝叶斯置信神经网络传播，和多项目伽玛泊松收缩器。Venn分析用于比较和选择常见和特定的AE。
结果：本研究包括73,042例接受帕博西尼治疗的患者，25,142与ribociclib，7563和abemaciclib。所有三种抑制剂均具有27种常见的AE。Palbociclib表现出最高的血液毒性ROR，虽然ribociclib对巨细胞病的ROR最高，指甲疾病,和肝脏病变。Abemaciclib表现出最高的粘膜毒性ROR。palbociclib和ribociclib的共同信号包括血液学毒性，免疫反应性降低，和口疮溃疡。骨髓抑制,口腔疼痛,假性肝硬化是palbociclib和abemaciclib的常见信号。贫血,肝毒性，观察到肺炎是ribociclib和abemaciclib的常见信号。此外，与palbociclib相关的特定AE包括疲劳，脱发,和口腔炎。对于ribociclib，特异性AE包括心电图QT延长，血小板减少症,和减少血红蛋白。Abemaciclib特别与腹泻有关，呕吐,和间质性肺病.
结论：我们的分析显示palbociclib表现出更高的血液学毒性风险。Ribociclib显示出较高的肝毒性风险，肾毒性，和QT延长。Abemaciclib显示肝毒性的风险更高，胃肠道的影响，间质性肺病,和血栓形成。这些发现为CDK4/6抑制剂选择提供了有价值的见解。
方法：分析FDA不良事件报告系统（2015-2022）中CDK4/6抑制剂的不良事件。使用四种不成比例的方法来检测安全性信号：报告优势比(ROR)，比例报告比率，贝叶斯置信神经网络传播，和多项目伽玛泊松收缩器。Venn分析用于比较和选择常见和特定的AE。
结果：本研究包括73,042例接受帕博西尼治疗的患者，25,142与ribociclib，7563和abemaciclib。所有三种抑制剂均具有27种常见的AE。Palbociclib表现出最高的血液毒性ROR，虽然ribociclib对巨细胞病的ROR最高，指甲疾病,和肝脏病变。Abemaciclib表现出最高的粘膜毒性ROR。palbociclib和ribociclib的共同信号包括血液学毒性，免疫反应性降低，和口疮溃疡。骨髓抑制,口腔疼痛,假性肝硬化是palbociclib和abemaciclib的常见信号。贫血,肝毒性，观察到肺炎是ribociclib和abemaciclib的常见信号。此外，与palbociclib相关的特定AE包括疲劳，脱发,和口腔炎。对于ribociclib，特异性AE包括心电图QT延长，血小板减少症,和减少血红蛋白。Abemaciclib特别与腹泻有关，呕吐,和间质性肺病.
结论：我们的分析显示palbociclib表现出更高的血液学毒性风险。Ribociclib显示出较高的肝毒性风险，肾毒性，和QT延长。Abemaciclib显示肝毒性的风险更高，胃肠道的影响，间质性肺病,和血栓形成。这些发现为CDK4/6抑制剂选择提供了有价值的见解。
