Cardiotoxicity and Cardiac Monitoring During Adjuvant Trastuzumab in Daily Dutch Practice: A Study of the Southeast Netherlands Breast Cancer Consortium

• Published in: The oncologist (Dayton, Ohio) Vol. 21; no. 5; pp. 555 - 562
• Main Authors: Seferina, Shanly C., Boer, Maaike, Derksen, M. Wouter, Berkmortel, Franchette, Kampen, Roel J.W., Wouw, Agnès J., Joore, Manuela, Peer, Petronella G.M., Voogd, Adri C., Tjan‐Heijnen, Vivianne C.G.
• Format: Journal Article
• Language: English
• Published: Durham, NC, USA AlphaMed Press 01.05.2016
• Subjects: Adjuvant trastuzumab; Adult; Antineoplastic Agents - adverse effects; Breast Cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cardiac monitoring; Cardiotoxicity; Cardiotoxicity - epidemiology; Chemotherapy, Adjuvant; Daily practice; Female; Humans; Incidence; Middle Aged; Neoplasm Staging; Receptor, ErbB-2 - analysis; Receptor, ErbB-2 - antagonists & inhibitors; Trastuzumab - adverse effects; Ventricular Function, Left - drug effects; Adjuvant trastuzumab; Cardiotoxicity; Cardiac monitoring; Daily practice
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1634/theoncologist.2015-0230

Introduction. We assessed the incidence and timing of first cardiac events, impact on trastuzumab prescription, and role of left ventricular ejection fraction (LVEF) monitoring in daily practice of trastuzumab‐treated patients with human epidermal growth receptor 2 (HER2)‐positive early breast cancer. Methods. We included all patients with stage I–III breast cancer diagnosed in the early years (2005–2007) after the introduction of adjuvant trastuzumab in five hospitals in Southeast Netherlands. We studied the incidence and timing of cardiotoxicity in patients treated with adjuvant trastuzumab, using similar cardiac endpoints as in the Herceptin Adjuvant (HERA) trial. Results. Of 2,684 included patients, 476 (17.7%) had a HER2‐positive tumor. Of these, 269 (56.9%) were treated with adjuvant chemotherapy, and of these, 230 (85.5%) also received trastuzumab. Cardiotoxicity was observed in 29 of 230 patients (12.6%). Twenty of the 230 patients (8.7%) had symptomatic cardiotoxicity, defined as a drop in LVEF of at least 10 percentage points and to below 50%, accompanied by symptoms of congestive heart failure. Trastuzumab was definitely discontinued because of supposed cardiotoxicity in 36 patients (15.6%), of whom only 15 (6.5%) had a significant LVEF drop. Of the 36 patients who prematurely discontinued trastuzumab (including the 29 in whom cardiotoxicity was observed), 84.8% stopped in the first 6 months. No cardiac deaths were seen. Conclusion. In the first years after implementation of trastuzumab for treatment of early breast cancer, physicians frequently based their decision to discontinue treatment on patient symptoms apart from LVEF outcome. We suggest that focusing LVEF monitoring on the first 6 months might be more cost‐effective without compromising patient safety. Nonetheless, further research is needed. Implications for Practice: Knowledge of when cardiotoxicity occurs in daily practice will help shape the best follow‐up method for cardiac monitoring in trastuzumab‐treated patients with human epidermal growth receptor 2‐positive early breast cancer. In the first years after implementation of trastuzumab for treatment of early breast cancer, physicians frequently based their decision to discontinue treatment on patient symptoms apart from left ventricular ejection fraction (LVEF) outcome. When cardiotoxicity was found in daily practice, it occurred mainly in the first 6 months after start of trastuzumab. This study suggests that focusing LVEF monitoring on the first 6 months might be more cost‐effective without compromising patient safety. This insight stresses the relevance of performing real‐world analyses. 摘要 引言. 对于临床上接受曲妥珠单抗治疗的人类表皮生长因子受体 2 (HER2) 阳性的早期乳腺癌患者, 我们对首次心脏事件的发生率和发生时机、对曲妥珠单抗处方的影响, 以及左心室射血分数 (LVEF) 监测的作用进行了评估。 方法. 本研究在荷兰东南部的 5 家医院中, 入选了在曲妥珠单抗辅助治疗用于临床实践后初期 (2005‐2007 年 ) 诊断的所有 I∼III 期乳腺癌患者。我们对接受曲妥珠单抗辅助治疗患者的心脏毒性发生率和发生时机进行了研究, 所用的心脏终点与赫赛汀辅助治疗 (HERA) 试验相同。 结果. 在入选的 2684 例患者中, 476 例 (17.7%) 为 HER2 阳性。其中 269 例 (56.9%) 接受辅助化疗, 这些患者中又有 230 例 (85.5%) 还接受了曲妥珠单抗治疗。在 29/230 例 (12.6%) 的患者中观察到心脏毒性。 20/230 例 (8.7%) 存在症状性心脏毒性 (定义为 LVEF 下降≥10% 且 LVEF<50%), 并伴有充血性心力衰竭症状。 36 例 (15.6%) 患者因推断发生心脏毒性而明确停止曲妥珠单抗治疗, 其中仅有 15 例 (6.5%) 出现显著的 LVEF 下降。在 36 例永久停用曲妥珠单抗 (包括 29 例观察到心脏毒性) 的患者中, 84.8%在治疗最初 6 个月内停药。研究未观察到心脏性死亡。 结论. 在曲妥珠单抗应用于早期乳腺癌治疗的最初数年间, 医生常根据患者症状 (而非LVEF转归) 决定停药。我们建议在治疗的最初6个月集中进行LVEF监测, 这样做可能经济效益更好, 而不会影响患者的安全性。但还是就此需要开展进一步的研究。The Oncologist 2016;21:555–562 对临床实践的提示: 在使用曲妥珠单抗对人类表皮生长因子受体 2 阳性早期乳腺癌患者进行治疗的日常实践中, 了解心脏毒性会在什么时候发生有助于对心脏监测的随访策略作出最佳调整。在曲妥珠单抗应用于早期乳腺癌治疗的最初数年中, 医生常根据患者症状, 而不是左心室射血分数 (LVEF) 转归决定停药。本研究建议在治疗的最初 6 个月集中进行 LVEF 监测, 这样做可能经济效益更好, 而不会影响患者的安全性。本文的观点强调了开展真实世界分析的现实意义。 The incidence and timing of first cardiac events, impact on trastuzumab prescription, and role of left ventricular ejection fraction (LVEF) monitoring in trastuzumab‐treated patients with HER2‐positive early breast cancer was assessed. Trastuzumab was discontinued in 36 of 230 patients because of cardiotoxicity; 15 of these had significantly reduced LVEF, and 84.8% stopped taking the drug within the first 6 months of initiating the therapy.