Department of Pharmacy, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences.
Anticancer Drugs. 2022 Jan 1;33(1):e228-e234. doi: 10.1097/CAD.0000000000001191.
Arrhythmias associated with antibody-drug conjugates (ADCs) are rare but potentially life-threatening adverse events (AEs). No study has systemically compared arrhythmias associations for various marketed ADCs. This needs to be clarified to guide antitumor therapies. We extracted data of patients treated with ADCs registered between 2004 q1 and 2020 q3 from the US Food and Drug Administration adverse event reporting system (FAERS). The medical dictionary for regulatory activities was used to identify arrhythmias cases. Disproportionality analysis was performed by calculating the reporting odds ratios (ROR) with corresponding 95% confidence intervals (95% CI). Clinical characteristics of patients with ADCs-associated arrhythmias and the time to onset of arrhythmias following different ADCs were collected. A total of 140 reports were considered after inclusion criteria were used. Exposure to gemtuzumab ozogamicin (2.23, 1.67-2.97; 48 cases) and brentuximab vedotin (1.27, 1.00-1.61; 67 cases) were associated with a positive signal of arrhythmia. The highest number of arrhythmia reports was for brentuximab vedotin (n = 67). Also 88.00% of arrhythmia occurred within 60 days for all these ADCs. Arrhythmia was commonly reported in patients with hematologic tumors and breast cancer. In the time to onset of adverse events after administration, brentuximab vedotin was significantly earlier than gemtuzumab ozogamicin (38.21 vs. 40.50 days; P = 0.0093), and gemtuzumab ozogamicin was significantly earlier than trastuzumab emtansine (40.50 vs. 147.50 days; P = 0.0035). We reviewed arrhythmia adverse drug reactions associated with ADCs from the FAERS database. This study is practical for clinicians to enhance the management of arrhythmia associated with ADCs and improve ADCs treatment safety.
抗体药物偶联物（ADCs）相关的心律失常罕见但具有潜在致命性的不良事件（AEs）。目前尚无研究系统比较各种已上市 ADC 相关心律失常的发生情况。为指导抗肿瘤治疗，有必要对此加以澄清。我们从美国食品和药物管理局不良事件报告系统（FAERS）中提取了 2004 年第 1 季度至 2020 年第 3 季度期间注册的 ADC 治疗患者的数据。采用监管活动医学词典识别心律失常病例。通过计算报告比值比（ROR）及其相应的 95%置信区间（95%CI）进行比例失调分析。收集了 ADC 相关心律失常患者的临床特征以及不同 ADC 后心律失常的发病时间。纳入标准后共考虑了 140 份报告。吉妥珠单抗奥佐米星（2.23，1.67-2.97；48 例）和本妥昔单抗维迪辛（1.27，1.00-1.61；67 例）的暴露与心律失常的阳性信号相关。报告心律失常的数量最多的是本妥昔单抗维迪辛（n=67）。此外，所有这些 ADC 的心律失常发生率在 60 天内均达到 88.00%。心律失常常见于血液系统肿瘤和乳腺癌患者。在给药后不良事件的发生时间上，本妥昔单抗维迪辛明显早于吉妥珠单抗奥佐米星（38.21 对 40.50 天；P=0.0093），吉妥珠单抗奥佐米星明显早于曲妥珠单抗恩美坦辛（40.50 对 147.50 天；P=0.0035）。我们从 FAERS 数据库中回顾了与 ADC 相关的心律失常不良药物反应。该研究对临床医生增强 ADC 相关心律失常的管理和提高 ADC 治疗安全性具有实际意义。
