Dilawari Asma, Krantz Mori J, Bulatao Ilynn, Joeng Hee-Koung, Neilson Marc, Wedam Suparna, Gao Xin, Fiero Mallorie H, Nair Abhilasha, Theoret Marc, Amiri-Kordestani Laleh
Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Oncology Center of Excellence (OCE), U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Ann Noninvasive Electrocardiol. 2025 May;30(3):e70087. doi: 10.1111/anec.70087.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. By releasing blocks (checkpoints) on the immune system, they elicit powerful antitumor effects. Despite improving survival, ICIs are associated with serious cardiac toxicities. Previous reports have focused on advanced cancer; cardiotoxicity data are therefore limited in the curative setting. We evaluated ICI cardiotoxicity in the non-metastatic setting, where long-term cardiac safety is a growing public health concern.
ICIs approved in the adjuvant setting were pooled and trials with combination chemotherapy were excluded. Cardiac adverse events (AEs) and emerging cardio-metabolic risks (hyperglycemia, weight gain, hypothyroidism) were assessed. The relative risk (RR) of cardiotoxicity was assessed.
Ten randomized controlled trials of atezolizumab, ipilimumab, nivolumab, and pembrolizumab in multiple solid tumors were evaluated; among 9244 patients, 5338 received ICIs. No trial performed routine cardiac monitoring. Six percent of ICI patients vs. 4.6% in placebo (RR 1.24, 95% CI 1.04, 1.49) had a cardiac AE and 13 (0.2%) of ICI patients experienced a fatal cardiac AE (RR 4.76, 95% CI 1.07, 21.06). Older age and male sex were associated with a higher risk for cardiac fatality. Arrhythmia was the most common cardiac AE; hypothyroidism was more frequent (14% vs. 2.5%) among ICI-treated patients.
This is the largest pooled analysis of cardiac AEs associated with ICIs in the adjuvant setting. Despite no formalized testing for subclinical cardiotoxicity, ICI treatment increased cardiac AEs. These findings are relevant for long-term cancer survivors, clinicians, and particularly in new drug development, where cardiotoxicity may be substantially underestimated.
免疫检查点抑制剂（ICI）彻底改变了癌症治疗方式。通过解除免疫系统上的阻断（检查点），它们引发强大的抗肿瘤作用。尽管提高了生存率，但ICI与严重的心脏毒性相关。以往的报告主要集中在晚期癌症；因此，在治愈性治疗环境中心脏毒性数据有限。我们评估了非转移性环境中ICI的心脏毒性，在这种环境中，长期心脏安全性日益受到公共卫生关注。
汇总在辅助治疗中获批的ICI，并排除联合化疗的试验。评估心脏不良事件（AE）和新出现的心脏代谢风险（高血糖、体重增加、甲状腺功能减退）。评估心脏毒性的相对风险（RR）。
评估了阿替利珠单抗、伊匹木单抗、纳武利尤单抗和帕博利珠单抗在多种实体瘤中的10项随机对照试验；在9244例患者中，5338例接受了ICI治疗。没有试验进行常规心脏监测。6%的ICI患者与4.6%的安慰剂患者发生心脏AE（RR 1.24，95%CI 1.04，1.49），13例（0.2%）ICI患者发生致命性心脏AE（RR 4.76，95%CI 1.07，21.06）。年龄较大和男性与心脏死亡风险较高相关。心律失常是最常见的心脏AE；在接受ICI治疗的患者中，甲状腺功能减退更为常见（14%对2.5%）。
这是辅助治疗环境中与ICI相关的心脏AE的最大规模汇总分析。尽管没有对亚临床心脏毒性进行正式检测，但ICI治疗增加了心脏AE。这些发现与长期癌症幸存者、临床医生相关，特别是在新药研发中，在新药研发中心脏毒性可能被严重低估。
