title: Cardiac toxicity events in the PHARE trial, an adjuvant trastuzumab randomised phase III study.
abstract: BACKGROUND
  This article reports, the cardiac toxicity according to 6- versus 12-month durations of adjuvant trastuzumab in PHARE randomised trial (NCT00381901).
  
  
  METHODS
  Cardiac 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.
  
  
  RESULTS
  Among 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.
  
  
  CONCLUSIONS
  PHARE 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.
authors.affiliation: University Hospital J Minjoz, Besançon, France. Electronic address: xavier.pivot@univ-fcomte.fr.
authors.forename: Xavier
authors.initials: X
authors.lastname: Pivot
authors.affiliation: University Hospital, Bern, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Suter
authors.affiliation: Centre jean Perrin, Clermont-Ferrand, France.
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Nabholtz
authors.affiliation: Institut Curie, Paris, France.
authors.forename: Jean Yves
authors.initials: JY
authors.lastname: Pierga
authors.affiliation: University Hospital Saint-Louis, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Espie
authors.affiliation: Centre Catherine de Sienne, Nantes, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Lortholary
authors.affiliation: University Hospital Pitié Salpêtrière, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Khayat
authors.affiliation: French National Cancer Institut, Boulogne, France.
authors.forename: Iris
authors.initials: I
authors.lastname: Pauporte
authors.affiliation: Centre Val d'Aurelle, Montpellier, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Romieu
authors.affiliation: Centre Oscar Lambret, Lille, France.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kramar
authors.affiliation: Centre Georges François Leclerc, Dijon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D005602:France / Q000453:epidemiology; D006333:Heart Failure / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D015994:Incidence; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D000068878:Trastuzumab / Q000009:adverse effects*; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Adjuvant trastuzumab; Breast cancer; Cardiac Heart Failure; Cardiotoxicity; Randomised trial