Evandro de Azambuja1, Marion J Procter2, Dirk J van Veldhuisen2, Dominique Agbor-Tarh2, Otto Metzger-Filho2, Jutta Steinseifer2, Michael Untch2, Ian E Smith2, Luca Gianni2, Jose Baselga2, Christian Jackisch2, David A Cameron2, Richard Bell2, Brian Leyland-Jones2, Mitch Dowsett2, Richard D Gelber2, Martine J Piccart-Gebhart2, Thomas M Suter2. 1. 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. evandro.azambuja@bordet.be. 2. 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.
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.
RCT Entities:
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 humanepidermal 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.
Authors: Anthony F Yu; Roy B Mukku; Shivani Verma; Jennifer E Liu; Kevin C Oeffinger; Richard M Steingart; Clifford A Hudis; Chau T Dang Journal: Breast Cancer Res Treat Date: 2017-07-14 Impact factor: 4.872
Authors: Heikki Joensuu; Judith Fraser; Hans Wildiers; Riikka Huovinen; Päivi Auvinen; Meri Utriainen; Paul Nyandoto; Kenneth K Villman; Päivi Halonen; Helena Granstam-Björneklett; Lotta Lundgren; Liisa Sailas; Taina Turpeenniemi-Hujanen; Minna Tanner; Jeffrey Yachnin; Diana Ritchie; Oskar Johansson; Teppo Huttunen; Patrick Neven; Peter Canney; Vernon J Harvey; Pirkko-Liisa Kellokumpu-Lehtinen; Henrik Lindman Journal: JAMA Oncol Date: 2018-09-01 Impact factor: 31.777
Authors: A S Coates; E P Winer; A Goldhirsch; R D Gelber; M Gnant; M Piccart-Gebhart; B Thürlimann; H-J Senn Journal: Ann Oncol Date: 2015-05-04 Impact factor: 32.976
Authors: David Cameron; Martine J Piccart-Gebhart; Richard D Gelber; Marion Procter; Aron Goldhirsch; Evandro de Azambuja; Gilberto Castro; Michael Untch; Ian Smith; Luca Gianni; Jose Baselga; Nedal Al-Sakaff; Sabine Lauer; Eleanor McFadden; Brian Leyland-Jones; Richard Bell; Mitch Dowsett; Christian Jackisch Journal: Lancet Date: 2017-02-17 Impact factor: 79.321