REVIEW OF HERCEPTIN CARDIOTOXICITY

J Clin Oncol. 2010 Jun 7. [Epub ahead of print]
Longer-Term Assessment of Trastuzumab-Related Cardiac Adverse Events in the Herceptin Adjuvant (HERA) Trial.
Procter M, Suter TM, de Azambuja E, Dafni U, van Dooren V, Muehlbauer S, Climent MA, Rechberger E, Liu WT, Toi M, Coombes RC, Dodwell D, Pagani O, Madrid J, Hall M, Chen SC, Focan C, Muschol M, van Veldhuisen DJ, Piccart-Gebhart MJ.

Frontier Science Scotland, Kincraig, Kingussie; Imperial College London, London; and St James's Institute of Oncology, St James Hospital, Leeds; and Heathwood and Wexham Park NHS Hospitals Foundation Trust and Mount Vernon Cancer Centre, Northwood, UK; Swiss Cardiovascular Center, University Hospital Bern; Institute of Oncology of Southern Switzerland, Bellinzona; and F. Hoffmann-La Roche, Basel, Switzerland; Institut Jules Bordet, Université Libre de Bruxelles; CHC-Clinique Saint-Joseph, Liege; and Breast European Adjuvant Studies Team, Brussels, Belgium; University of Athens; and Frontier Science Foundation Hellas, Athens, Greece; Instituto Valenciano de Oncologia, Valencia, Spain; Hospital Barmherzige Schwestern, Linz, Austria; National Institute of Cancer Research, National Health Research Institutes, Taipei; and Chang Gung Memorial Hospital, Chang Gung University Medical College, Taoyuan, Taiwan; Kyoto University, Kyoto, Japan; Hospital Militar, Servicio de Quimioterapia, Santiago, Chile; Kardiologische Praxis, Munich, Germany; and University Medical Center Groningen, Groningen, the Netherlands.
Abstract

PURPOSE We investigated the incidence of cardiac adverse events in patients with early breast cancer in the Herceptin Adjuvant (HERA) trial who were treated with 1 year of trastuzumab after completion of (neo)adjuvant chemotherapy. PATIENTS AND METHODS The HERA trial is a three-group, randomized trial that compared 1 year or 2 years of trastuzumab with observation in women with human epidermal growth factor receptor-2 (HER2) -positive early breast cancer. Eligible patients had normal left ventricular ejection fraction (LVEF; >/= 55%) after completion of (neo)adjuvant chemotherapy with or without radiotherapy. Cardiac function was monitored throughout the trial. This analysis considers patients randomly assigned to 1 year of trastuzumab treatment or observation. Results There were 1,698 patients randomly assigned to observation and 1,703 randomly assigned to 1 year of trastuzumab treatment; 94.1% of patients had been treated with anthracyclines. The incidence of discontinuation of trastuzumab because of cardiac disorders was low (5.1%). At a median follow-up of 3.6 years, the incidence of cardiac end points remained low, though it was higher in the trastuzumab group than in the observation group (severe CHF, 0.8% v 0.0%; confirmed significant LVEF decreases, 3.6% v 0.6%) In the trastuzumab group, 59 of 73 patients with a cardiac end point reached acute recovery; of these 59 patients, 52 were considered by the cardiac advisory board (CAB) to have a favorable outcome from the cardiac end point. CONCLUSION The incidence of cardiac end points remains low even after longer-term follow-up. The cumulative incidence of any type of cardiac end point increases during the scheduled treatment period of 1 year, but it remains relatively constant thereafter.