Brown Lauren J, Meredith Thomas, Yu Jie, Patel Anushka, Neal Bruce, Arnott Clare, Lim Elgene
Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
St Vincent's Hospital, Sydney, NSW 2010, Australia.
Cancers (Basel). 2021 Nov 3;13(21):5527. doi: 10.3390/cancers13215527.
Monoclonal antibodies including trastuzumab, pertuzumab, and antibody-drug conjugates, form the backbone of HER2-positive breast cancer therapy. Unfortunately, an important adverse effect of these agents is cardiotoxicity, occurring in approximately 10% of patients. There is increasing published data regarding prevention strategies for cardiotoxicity, though seldom used in clinical practice. We performed a systematic review and meta-analysis of randomized-controlled trials to evaluate pharmacotherapy for the prevention of monoclonal HER2-directed antibody-induced cardiotoxicity in patients with breast cancer. Online databases were queried from their inception until October 2021. Effects were determined by calculating risk ratios (RRs) and 95% confidence intervals (CI) or mean differences (MD) using random-effects models. We identified five eligible trials. In the three trials ( = 952) reporting data on the primary outcome of cardiotoxicity, there was no clear effect for patients assigned active treatment compared to control (RR = 0.90, 95% CI 0.63 to 1.29, = 0.57). Effects were similar for ACE-I/ARB and beta-blockers ( homogeneity = 0.50). Active treatment reduced the risk of HER2 therapy interruptions (RR = 0.57, 95% CI 0.43 to 0.77, < 0.001) with similar findings for ACE-I/ARB and beta-blockers ( homogeneity = 0.97). Prophylactic treatment with ACE-I/ARB or beta-blocker therapy may be of value for cardio-protection in patients with breast cancer prescribed monoclonal antibodies. Further, adequately powered randomized trials are required to define the role of routine prophylactic treatment in this patient group.
包括曲妥珠单抗、帕妥珠单抗在内的单克隆抗体以及抗体药物偶联物，构成了HER2阳性乳腺癌治疗的核心。不幸的是，这些药物的一个重要不良反应是心脏毒性，约10%的患者会出现。关于心脏毒性预防策略的已发表数据越来越多，但在临床实践中很少使用。我们对随机对照试验进行了系统评价和荟萃分析，以评估药物治疗对预防乳腺癌患者单克隆HER2导向抗体诱导的心脏毒性的效果。从各在线数据库建立至2021年10月进行查询。采用随机效应模型计算风险比（RRs）和95%置信区间（CIs）或均值差（MD）来确定疗效。我们确定了五项符合条件的试验。在三项报告心脏毒性主要结局数据的试验（n = 952）中，与对照组相比，接受活性治疗的患者没有明显效果（RR = 0.90，95% CI 0.63至1.29，P = 0.57）。ACE-I/ARB和β受体阻滞剂的效果相似（I²同质性 = 0.50）。活性治疗降低了HER2治疗中断的风险（RR = 0.57，95% CI 0.43至0.77，P < 0.001），ACE-I/ARB和β受体阻滞剂的结果相似（I²同质性 = 0.97）。对于接受单克隆抗体治疗的乳腺癌患者，使用ACE-I/ARB或β受体阻滞剂进行预防性治疗可能对心脏有保护作用。此外，需要有足够样本量的随机试验来确定常规预防性治疗在该患者群体中的作用。
