Background: Human epidermal growth receptor 2 (HER2) targeted therapies have survival benefit in adjuvant and metastatic HER2 positive breast cancer but are associated with cardiac dysfunction. Current U.S. Food and Drug Administration recommendations limit the use of HER2 targeted agents to patients with normal left ventricular (LV) systolic function.
Methods: The objective of the SAFE-HEaRt study is to evaluate the cardiac safety of HER2 targeted therapy in patients with HER2 positive breast cancer and mildly reduced left ventricular ejection fraction (LVEF) with optimized cardiac therapy. Thirty patients with histologically confirmed HER2 positive breast cancer (stage I-IV) and reduced LVEF (40% to 49%) who plan to receive HER2 targeted therapy for ≥3 months will be enrolled. Prior to initiation on study, optimization of heart function with beta-blockers and angiotensin converting enzyme inhibitors will be initiated. Patients will be followed by serial echocardiograms and cardiac visits during and 6 months after completion of HER2 targeted therapy. Myocardial strain and blood biomarkers, including cardiac troponin I and high-sensitivity cardiac troponin T, will be examined at baseline and during the study.
Discussion: LV dysfunction in patients with breast cancer poses cardiac and oncological challenges and limits the use of HER2 targeted therapies and its oncological benefits. Strategies to prevent cardiac dysfunction associated with HER2 targeted therapy have been limited to patients with normal LVEF, thus excluding patients who may receive the highest benefit from those strategies. SAFE-HEaRt is the first prospective pilot study of HER2 targeted therapies in patients with reduced LV function while on optimized cardiac treatment that can provide the basis for clinical practice changes. The Oncologist 2017;22:518-525 IMPLICATIONS FOR PRACTICE: Human epidermal growth receptor 2 (HER2) targeted therapies have survival benefit in adjuvant and metastatic HER2 positive breast cancer but are associated with cardiac dysfunction. To our knowledge, SAFE-HEaRt is the first clinical trial that prospectively tests the hypothesis that HER2 targeted therapies may be safely administered in patients with mildly reduced cardiac function in the setting of ongoing cardiac treatment and monitoring. The results of this study will provide cardiac safety data and inform consideration of clinical practice changes in patients with HER2 positive breast cancer and reduced cardiac function, as well as provide information regarding cardiovascular monitoring and treatment in this population.
摘要
背景. 人类表皮生长因子受体2（HER2）靶向药物辅助治疗可为转移性HER2阳性乳腺癌患者带来生存获益, 但也会引起心脏功能障碍。根据美国食品药品监督管理局的现行建议, HER2靶向药物仅可用于左心室（LV）收缩功能正常的患者。
方法. SAFE‐HEaRt 研究的目的是在接受最佳心脏治疗且左心室射血分数（LVEF）轻度降低的HER2阳性乳腺癌患者中评价HER2靶向治疗的心脏安全性。将入组30例经组织学证实为HER2阳性乳腺癌（I–IV期）且LVEF降低（40%‐49%）的患者, 上述患者计划接受≥3个月的HER2靶向治疗。在开始研究前, 首先使用β‐受体阻滞剂和血管紧张素转换酶抑制剂进行治疗, 从而使心脏功能达到最佳。在HER2靶向治疗期间以及治疗结束后6个月, 通过连续超声心动图和心脏专科访视对患者进行随访。在基线时和研究期间检查心肌应变和血液生物标志物, 后者包括心肌肌钙蛋白I和高灵敏度心肌肌钙蛋白T。
讨论 乳腺癌患者的LV功能障碍为心脏和肿瘤学领域带来了挑战, 并且限制了HER2靶向治疗的应用及其肿瘤学获益。为了预防与HER2靶向治疗相关的心脏功能障碍, 该治疗仅限于LVEF正常的患者, 从而排除了潜在获益最高的患者。SAFE‐HEaRt是HER2靶向治疗首次用于接受最佳心脏治疗的LV功能降低患者的前瞻性初步研究, 可为临床实践的变更提供依据。The Oncologist 2017;22:518–525
对临床实践的提示：人类表皮生长因子受体2（HER2）靶向药物辅助治疗可为转移性HER2阳性乳腺癌患者带来生存获益, 但也会引起心脏功能障碍。据我们所知, SAFE‐HEaRt是第一项前瞻性检验以下假设的临床试验：HER2靶向治疗在持续接受心脏治疗并监测心脏功能的情况下可以安全用于心脏功能轻度降低的患者。此项研究的结果将提供HER2靶向治疗在心脏功能降低的HER2阳性乳腺癌患者中的心脏安全性数据, 并提示我们考虑变更临床实践, 此外还将提供该人群心血管监测和治疗的相关信息。
Keywords: Breast cancer; Cardiotoxicity; Clinical trial; Molecular targeted therapy.
© AlphaMed Press 2017.