Trastuzumab-Associated Cardiac Events at 8 Years of Median Follow-Up in the Herceptin Adjuvant Trial (BIG 1-01)

Evandro de Azambuja*, Marion J. Procter, Dirk J. van Veldhuisen, Dominique Agbor-Tarh, Otto Metzger-Filho, Jutta Steinseifer, Michael Untch, Ian E. Smith, Luca Gianni, Jose Baselga, Christian Jackisch, David A. Cameron, Richard Bell, Brian Leyland-Jones, Mitch Dowsett, Richard D. Gelber, Martine J. Piccart-Gebhart, Thomas M. Suter

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2159-2165
Number of pages9
JournalJournal of Clinical Oncology
Volume32
Issue number20
DOIs
Publication statusPublished - 10 Jul 2014

Keywords

  • HER2-POSITIVE BREAST-CANCER
  • RANDOMIZED CONTROLLED-TRIAL
  • HEART-FAILURE
  • CHEMOTHERAPY
  • CARDIOTOXICITY
  • THERAPY
  • ERBB2
  • PLUS
  • DOXORUBICIN
  • PACLITAXEL

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