曲妥珠单抗辅助治疗 8 年的中位随访时发生的心脏不良事件：赫赛汀辅助治疗研究（BIG 1-01）。

Trastuzumab-associated cardiac events at 8 years of median follow-up in the Herceptin Adjuvant trial (BIG 1-01).

机构信息

Evandro de Azambuja and Martine J. Piccart-Genhart, Institut Jules Bordet; Evandro de Azambuja, Breast European Adjuvant Study Team; Martine J. Piccart-Gebhart, Université Libre de Bruxelles, Brussels, Belgium; Marion J. Procter and Dominique Agbor-Tarh, Frontier Science Scotland, Kincraig, Kingussie; David A. Cameron, University of Edinburgh and Western General Hospital, Edinburgh; Ian E. Smith, Royal Marsden Hospital and the Institute of Cancer Research; Mitch Dowsett, the Royal Marsden National Health Service Trust, London, United Kingdom; Dirk J. van Veldhuisen, University of Groningen, Groningen, the Netherlands; Otto Metzger-Filho and Richard D. Gelber, Dana-Farber Cancer Institute, Boston, MA; Jutta Steinseifer, F. Hoffmann-La Roche, Basel; Thomas M. Suter, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, Bern, Switzerland; Michael Untch, HELIOS Klinikum Berlin, Buch; Christian Jackisch, Klinikum Offenbach, Offenbach, Germany; Luca Gianni, San Raffaele Institute, Milan, Italy; Jose Baselga, Memorial Sloan Kettering Cancer Center, New York, NY; Richard Bell, Andrew Love Cancer Centre, Geelong Hospital, Geelong, Australia; and Brian Leyland-Jones, Edith Sanford Breast Cancer Research Institute, Sioux Falls, SD.

出版信息

J Clin Oncol. 2014 Jul 10;32(20):2159-65. doi: 10.1200/JCO.2013.53.9288. Epub 2014 Jun 9.

DOI:10.1200/JCO.2013.53.9288

PMID:24912899

Abstract

PURPOSE

To document the rate and outcome of trastuzumab-associated cardiac dysfunction in patients following 1 or 2 years of adjuvant therapy.

PATIENTS AND METHODS

The Herceptin Adjuvant (HERA) trial is a three-arm, randomized trial comparing 2 years or 1 year of trastuzumab with observation in 5,102 patients with human epidermal growth factor receptor 2 (HER2) -positive early-stage breast cancer. Cardiac function was closely monitored. Eligible patients had left ventricular ejection fraction (LVEF) ≥ 55% at study entry following neoadjuvant chemotherapy with or without radiotherapy. This 8-year median follow-up analysis considered patients randomly assigned to 2 years or 1 year of trastuzumab or observation.

RESULTS

The as-treated safety population for 2 years of trastuzumab (n = 1,673), 1 year of trastuzumab (n = 1,682), and observation (n = 1,744) is reported. Cardiac adverse events leading to discontinuation of trastuzumab occurred in 9.4% of patients in the 2-year arm and 5.2% of patients in the 1-year arm. Cardiac death, severe congestive heart failure (CHF), and confirmed significant LVEF decrease remained low in all three arms. The incidence of severe CHF (0.8%, 0.8%, and 0.0%, respectively) and confirmed significant LVEF decrease (7.2%, 4.1%, and 0.9%, respectively) was significantly higher in the 2-year and 1-year trastuzumab arms compared with the observation arm. Severe CHF was the same for 2-year and 1-year trastuzumab. Of patients with confirmed LVEF decrease receiving 2-year trastuzumab, 87.5% reached acute recovery. Of patients with confirmed LVEF decrease receiving 1-year trastuzumab, 81.2% reached acute recovery.

CONCLUSION

Long-term assessment at 8-year median follow-up confirms the low incidence of cardiac events for trastuzumab given sequentially after chemotherapy and radiotherapy, and cardiac events were reversible in the vast majority of patients.

摘要

目的

记录曲妥珠单抗辅助治疗 1 或 2 年后患者发生曲妥珠单抗相关性心脏功能障碍的发生率和结局。

方法

HER2 阳性早期乳腺癌患者接受曲妥珠单抗辅助治疗 2 年或 1 年与观察的随机对照的 Herceptin Adjuvant（HERA）试验共纳入 5102 例患者。密切监测心脏功能。入组患者接受新辅助化疗（包括或不包括放疗）后左心室射血分数（LVEF）≥55%。本 8 年中位随访分析纳入随机分配至曲妥珠单抗治疗 2 年或 1 年或观察的患者。

结果

报告了曲妥珠单抗治疗 2 年（n=1673）、1 年（n=1682）和观察（n=1744）的实际安全性人群。2 年治疗组中，有 9.4%的患者发生导致曲妥珠单抗停药的心脏不良事件，而 1 年治疗组中为 5.2%。所有 3 个治疗组中心脏死亡、严重充血性心力衰竭（CHF）和确诊的 LVEF 下降均保持低水平。严重 CHF（分别为 0.8%、0.8%和 0.0%）和确诊的 LVEF 下降（分别为 7.2%、4.1%和 0.9%）的发生率在 2 年和 1 年曲妥珠单抗治疗组中明显高于观察组。严重 CHF 在 2 年和 1 年曲妥珠单抗治疗组中相同。接受 2 年曲妥珠单抗治疗且确诊 LVEF 下降的患者中，87.5%达到急性恢复。接受 1 年曲妥珠单抗治疗且确诊 LVEF 下降的患者中，81.2%达到急性恢复。