Cardiac toxicity events in the PHARE trial,an adjuvant trastuzumab randomised phase III study |
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| Affiliation: | 1. University Hospital J Minjoz, Besançon, France;2. University Hospital, Bern, Switzerland;3. Centre jean Perrin, Clermont-Ferrand, France;4. Institut Curie, Paris, France;5. University Hospital Saint-Louis, Paris, France;6. Centre Catherine de Sienne, Nantes, France;7. University Hospital Pitié Salpêtrière, Paris, France;8. French National Cancer Institut, Boulogne, France;9. Centre Val d’Aurelle, Montpellier, France;10. Centre Oscar Lambret, Lille, France;11. Centre Georges François Leclerc, Dijon, France;1. Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy;2. Fondazione Michelangelo, Milano, Italy;3. Radiotherapy Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy;4. Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy;5. Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy;6. Breast Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy;1. Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea;2. Division of Hematology-Oncology, Department of Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan, Republic of Korea;3. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;4. Division of Hematology/Oncology, Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea;5. Division of Hematology-Oncology, Department of Internal Medicine, Soonchunhyang University Hospital Cheonan, Cheonan, Republic of Korea;1. University of California, Los Angeles (UCLA), Los Angeles, CA, USA;2. Department of Medical Oncology, Institut Gustave Roussy, Université Paris Sud, Villejuif, France;3. Beijing 307 Hospital of PLA, Beijing, China;4. Department of Breast Surgery, Cancer Hospital of Fudan University, Shanghai, China;5. Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil;6. Instituto Nacional de Enfermedades Neoplasicas, Surquillo, Lima, Peru;7. Taipei Veterans General Hospital, National Yang Ming University, Taipei, Taiwan;8. Department of Medical Oncology, Tumor Hospital of Harbin Medical University, Harbin, China;9. Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China;10. Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China;11. Department of Medical Oncology, University of Pretoria, Gauteng, South Africa;12. Sarah Cannon Research Institute, Nashville, Tennessee, USA;13. Department of Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan;14. International Drug Development Institute, Louvain La Neuve, Belgium;15. Translational Research in Oncology (TRIO), Paris, France;p. Translational Research in Oncology (TRIO), Edmonton, Canada;q. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA;r. Novartis Pharma AG, Basel, Switzerland;1. Center for Oncology and Hematology, Wilhelminen Hospital, Vienna, Austria;2. Massachusetts General Hospital Biostatistics Center, Boston, MA, USA;3. Royal Marsden Hospital, London, UK;4. Baylor Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, TX, USA;5. Rigshospitalet, DBCG Secretariat, Copenhagen, Denmark;6. Mater Hospital, North Sydney, NSW, Australia;7. University of Texas MD Anderson Cancer Center, Houston, TX, USA;8. Centre GF Leclerc, Dijon, France;9. Northwestern University, Chicago, IL, USA;10. Hospital Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain;11. Massachusetts General Hospital, Boston, MA, USA;12. Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium;13. Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada;14. Arizona Oncology, US Oncology, Sedona, AZ, USA;15. GlaxoSmithKline, Collegeville, PA, USA;1. Institut Jules Bordet and Breast European Adjuvant Study Team, Brussels, Belgium;2. Frontier Science (Scotland) Ltd, Grampian View, Kincraig, Kingussie, UK;3. Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium;4. Istituto Nazionale del Tumori, Milan, Italy;5. SOLTI Breast Cancer Research Group, Spain;6. GlaxoSmithKline, Collegeville, PA, USA;7. Clinic for Gynaecology, Gynaecologic Oncology and Obstetrics and Breast Cancer Centre, HELIOS Klinikum Berlin, Buch, Germany;8. Sana Klinikum Offenbach, Offenbach, Germany;9. National Institute of Oncology, Budapest, Hungary;10. Royal Marsden Hospital, London, UK;11. Institute of Cancer Research, London, UK;12. Patricia Ritchie Centre for Cancer Care and Research, The University of Sydney, Mater Hospital, North Sydney, NSW, Australia;13. Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China;14. PUC-RS School of Medicine, Porto Alegre, Brazil;15. Mayo Clinic, Jacksonville, FL, USA;p. Asian Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;q. Kliniken Essen-Mitte, Essen, Germany;r. National Taiwan University Hospital, Taipei, Taiwan;s. Clinique St-Elisabeth, Namur, Belgium;t. Mackay Memorial Hospital, Taipei, Taiwan;u. Kashirskoye Shosse, Moscow, Russia;v. Cancer Institute “Prof Dr Ion Chiricuta”, Cluj-Napoca, Romania;w. Department of Medical Oncology, University of Pretoria, Pretoria, South Africa;x. Odessa Oncology Centre, Odessa, Ukraine;y. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Frontier Science and Technology Research Foundation, Boston, MA, USA;z. University Hospital Kiel, Kiel, Germany;11. Memorial Sloan-Kettering Cancer Center, New York, NY, USA;1. Instituto de Investigación Sanitaria Gregorio Marañón, Grupo Español de Investigación en Cáncer de Mama (GEICAM), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Universidad Complutense, Madrid, Spain;2. Texas Oncology, Houston, TX, USA;3. Rigshospitalet, Copenhagen, Denmark;4. Institut Gustave Roussy, Villejuif, France;5. Massachusetts General Hospital Cancer Center, Boston, MA, USA;6. Aichi Cancer Center, Chikusa-ku, Nagoya, Japan;7. Luisenkrankenhaus, German Breast Group Forschungs GmbH, Düsseldorf, Neulsenburg, Germany;8. BC Cancer Agency, Vancouver, BC, Canada;9. Guy''s and St Thomas'' Hospital National Health Service Foundation Trust and Biomedical Research Centre, King''s College, London, UK;10. Pontifical Catholic University of Rio Grande do Sul School of Medicine, Porto Alegre, Brazil;11. Department of Surgery and Comprehensive Cancer Centre, Medical University of Vienna, Vienna, Austria;12. Daily Chemotherapy Hospital, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia;13. Virginia Cancer Specialists, Arlington, VA, USA;14. University Hospital for Tumors, University Hospital Center “Sestre milosrdnice”, Zagreb, Croatia;15. Ege University Faculty of Medicine, Izmir, Turkey;p. Auckland Hospital, Auckland, New Zealand;p. Oncology Department, Hospital Universitario Virgen del Rocio, Seville, Spain;r. Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;s. Department of Oncology, Lillebaelt Hospital, Vejle, Denmark;t. Oncology Institute of Vilnius University, Vilnius, Lithuania;u. Breast Oncology, Saitama Cancer Center, Kita-Adachi, Japan;v. Oncologianova GmbH, Recklinghausen, Germany;w. Department of Medical Oncology, Amphia Hospital, Breda, Netherlands;x. Department of Oncology, Christie Hospital Manchester, Manchester, UK;y. Breastlink Medical Group Inc, Santa Ana, CA, USA;z. University of Alberta, Department of Oncology, Cross Cancer Institute, Edmonton, AB, Canada;11. Puma Biotechnology Inc, Los Angeles, CA, USA;12. International Drug Development Institute, Louvain-la-Neuve, Belgium;13. Breast Cancer Research Centre–Western Australia, Perth, WA, Australia;14. Curtin University, Perth, WA, Australia |
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| Abstract: | BackgroundThis article reports, the cardiac toxicity according to 6- versus 12-month durations of adjuvant trastuzumab in PHARE randomised trial (NCT00381901).Patients and methodsCardiac follow-up and Left Ventricular Ejection Fraction (LVEF) assessment by echocardiography or multigated acquisition scan were performed every 3 months while patients received trastuzumab and after completion of treatment over the first 2 years and every 6 months afterwards. The primary cardiac end-point was Cardiac Heart Failure (CHF) defined as New York Heart Association (NYHA) class III or IV. The secondary cardiac end-points were: cardiac events, cardiac dysfunctions defined by NYHA class I and II; LVEF decreases, cardiac recoveries. The cardiac subcommittee reviewed cardiac events and assessed if patients had favourable outcomes or not on the basis of trends from LVEF measurements.ResultsAmong 3380 patients the cardiac dysfunction assessment included 14,055 and 13,218 LVEF measurements in the 12- and 6-month arms. The overall incidences of CHF were 0.65% (11/1690) and 0.53% (9/1690) in the 12 and 6 month arms, respectively (p > 0.05). Cardiac dysfunction occurred in 5.9% (100/1690) and 3.4% (58/1690) of patients in the 12 and 6 month arms, respectively (p = 0.001). Recoveries were observed for the majority patients and 0.79% (27/3380) of patients experienced an unfavourable cardiac outcome.ConclusionPHARE confirm that the incidence of cardiac end-points remains low and mostly reversible after trastuzumab. Identification at baseline of cardiac risk categories of patients should be of interest to provide an optimal adaptation of adjuvant modalities and a shorter duration might be an option. |
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| Keywords: | Breast cancer Adjuvant trastuzumab Cardiotoxicity Cardiac Heart Failure Randomised trial |
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