Legallois Damien, Da Silva Angélique, Alexandre Joachim, Milliez Paul, Sabatier Rémi, Blanchart Katrien, Plane Anne-Flore, Font Jonaz, Chrétien Basile, Dolladille Charles
Normandie Univ, UNICAEN, INSERM U1086 ANTICIPE, Avenue de la Côte de Nacre, F-14000 Caen, France.
Department of Cardiology, Caen-Normandy University Hospital, PICARO Cardio-Oncology Program, Avenue de la Côte de Nacre, F-14000 Caen, France.
Eur Heart J Cardiovasc Pharmacother. 2025 Aug 12;11(5):459-468. doi: 10.1093/ehjcvp/pvaf027.
Therapeutic advancements have significantly enhanced cancer patient survival rates yet concomitantly increased the prevalence of associated toxicities, such as cancer therapy-related cardiac dysfunction (CTRCD), either symptomatic (heart failure) or not. Using the World Health Organization's VigiBase® individual case safety report database, the aim was to establish the association between anticancer drugs and CTRCD reporting.
This study was a disproportionality analysis conducted in VigiBase® from the initial report of any anticancer drug until 29 February 2024. Reporting odds ratios for CTRCD were evaluated using a stepwise selection procedure and multivariable-adjusted analyses. Subsequently, secondary analyses consisted of the description of CTRCD cases associated with the identified anticancer drugs. ClinicalTrials.gov registration number: NCT06268535. Among 36 580 288 database reports, 42 828 CTRCD cases associated with at least one anticancer drug were identified with death reported in 20.6% of cases (8833 CTRCD cases). Primary analysis revealed 25 anticancer drugs significantly associated with CTRCD reporting, with trastuzumab, doxorubicin, and bortezomib exhibiting the strongest associations. Cancer therapy-related cardiac dysfunction reporting was associated with kinase inhibitors, including BCR-ABL inhibitors, ibrutinib, and osimertinib. New signals were identified for trabectedin, clofarabine, fludarabine, entrectinib, gemtuzumab ozogamicin, and anagrelide. In contrast, immune checkpoint inhibitors and most anti-vascular endothelial growth factor therapies showed no association with CTRCD.
This disproportionality study identified 25 anticancer drugs significantly associated with CTRCD reporting, including new signals. It highlights discrepancies compared with drugs recommended for cardiac dysfunction evaluation in the 2022 ESC Guidelines. This underscores the importance of including CTRCD as a safety endpoint in cancer studies.
治疗进展显著提高了癌症患者的生存率，但同时也增加了相关毒性的发生率，如癌症治疗相关的心脏功能障碍（CTRCD），无论有无症状（心力衰竭）。本研究利用世界卫生组织的VigiBase®个体病例安全报告数据库，旨在确定抗癌药物与CTRCD报告之间的关联。
本研究是在VigiBase®中进行的不成比例分析，从任何抗癌药物的首次报告至2024年2月29日。使用逐步选择程序和多变量调整分析评估CTRCD的报告比值比。随后，二次分析包括对与已识别抗癌药物相关的CTRCD病例的描述。ClinicalTrials.gov注册号：NCT06268535。在36580288份数据库报告中，识别出42828例与至少一种抗癌药物相关的CTRCD病例，其中20.6%的病例（8833例CTRCD病例）报告了死亡。初步分析显示，25种抗癌药物与CTRCD报告显著相关，曲妥珠单抗、多柔比星和硼替佐米显示出最强的关联。癌症治疗相关的心脏功能障碍报告与激酶抑制剂有关，包括BCR-ABL抑制剂、伊布替尼和奥希替尼。还发现了曲贝替定、氯法拉滨、氟达拉滨、恩曲替尼、吉妥珠单抗奥唑米星和阿那格雷的新信号。相比之下，免疫检查点抑制剂和大多数抗血管内皮生长因子疗法与CTRCD无关。
这项不成比例研究确定了25种与CTRCD报告显著相关的抗癌药物，包括新信号。它突出了与2022年欧洲心脏病学会指南中推荐用于心脏功能障碍评估的药物相比的差异。这强调了将CTRCD作为癌症研究安全终点的重要性。
