Cardiovascular Safety Reporting in Contemporary Breast Cancer Clinical Trials.
Cardiovascular Safety Reporting in Contemporary Breast Cancer Clinical Trials.
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当代乳腺癌临床试验中的心血管安全性报告。
DOI：
10.1161/jaha.121.025206
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发表时间：
2022-08-02
影响因子：
5.4
通讯作者：
Butler, Javed
中科院分区：
文献类型：
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作者：
Hamid, Arsalan;Anker, Markus S.;Ruckdeschel, John C.;Khan, Muhammad Shahzeb;Tharwani, Arsal;Oshunbade, Adebamike A.;Kipchumba, Rodney K.;Thigpen, Samuel C.;Anker, Stefan D.;Fonarow, Gregg C.;Hall, Michael E.;Butler, Javed
在早期临床试验中，有几种癌症疗法与心血管损害有关。然而，一些对心血管的危害直到后期试验才显现出来。为了限制疾病间的变异性，我们将重点放在乳腺癌上。因此，我们评估了当代乳腺癌2期和3期临床试验中心血管安全监测的报告和结果。我们搜索了Embase和Medline的2期和3期乳腺癌药物治疗试验的记录。我们检查了排除标准作为心血管疾病、不良心血管事件报告的结果，以及通过心血管成像、心电图、肌钙蛋白或利钠肽进行的心血管安全性评估。采用Fisher‘s精确检验对报道进行比较。我们的研究包括50项临床试验。在42项(84%)试验中，患者因心血管疾病而被排除在外。心力衰竭是一个常见的排除标准(n=31；62%的试验)。在43个(86%)试验中报告了不良心血管事件。在23个(46%)试验中没有报道心血管安全性评估，而在任何试验中都没有报道利钠肽和肌钙蛋白评估。心血管安全性评估更多地出现在由行业资助的试验中(69.2%比0.0%；P<；0.001)，以及在使用靶向/免疫治疗药物的试验中(78.6%比22.7%，P<；0.001)。我们的发现表明，在当代晚期乳腺癌试验中，患有心血管疾病或常见心血管疾病的患者的代表性明显不足。此外，在这些试验中，心血管安全性不是常规监测。因此，当代乳腺癌临床试验可能低估了临床上使用的癌症药物治疗药物的心血管风险。
Several cancer therapies have been associated with cardiovascular harm in early‐phase clinical trials. However, some cardiovascular harms do not manifest until later‐phase trials. To limit interdisease variability, we focused on breast cancer. Thus, we assessed the reporting of cardiovascular safety monitoring and outcomes in phase 2 and 3 contemporary breast cancer clinical trials. We searched Embase and Medline records for phase 2 and 3 breast cancer pharmacotherapy trials. We examined exclusion criterion as a result of cardiovascular conditions, adverse cardiovascular event reporting, and cardiovascular safety assessment through cardiovascular imaging, ECG, troponin, or natriuretic peptides. Fisher's exact test was utilized to compare reporting. Fifty clinical trials were included in our study. Patients were excluded because of cardiovascular conditions in 42 (84%) trials. Heart failure was a frequent exclusion criterion (n=31; 62% trials). Adverse cardiovascular events were reported in 43 (86%) trials. Cardiovascular safety assessments were not reported in 23 (46%) trials, whereas natriuretic peptide and troponin assessments were not reported in any trial. Cardiovascular safety assessments were more frequently reported in industry‐funded trials (69.2% versus 0.0%; P<0.001), and in trials administering targeted/immunotherapy agents compared with only hormonal/conventional chemotherapy (78.6% versus 22.7%, P<0.001). Our findings demonstrate significant under‐representation of patients with cardiovascular conditions or prevalent cardiovascular disease in contemporary later‐phase breast cancer trials. Additionally, cardiovascular safety is not routinely monitored in these trials. Therefore, contemporary breast cancer clinical trials may possibly underestimate the cardiovascular risks of cancer pharmacotherapy agents for use in clinical practice.