HER2-positive; adjuvant; breast cancer; cardiotoxicity; pertuzumab; trastuzumab; Anthracyclines; Trastuzumab; Aged; Female; Humans; Anthracyclines/adverse effects; Stroke Volume; Ventricular Function, Left; Breast Neoplasms/drug therapy; Breast Neoplasms; Oncology; Cancer Research
Abstract :
[en] [en] BACKGROUND: Trastuzumab increases the incidence of cardiac events (CEs) in patients with breast cancer (BC). Dual blockade with pertuzumab (P) and trastuzumab (T) improves BC outcomes and is the standard of care for high-risk human epidermal growth factor receptor 2 (HER2)-positive early BC patients. We analyzed the cardiac safety of P and T in the phase III APHINITY trial.
PATIENTS AND METHODS: Left ventricular ejection fraction (LVEF) ≥ 55% was required at study entry. LVEF assessment was carried out every 3 months during treatment, every 6 months up to month 36, and yearly up to 10 years. Primary CE was defined as heart failure class III/IV and a significant decrease in LVEF (defined as ≥10% from baseline and to <50%), or cardiac death. Secondary CE was defined as a confirmed significant decrease in LVEF, or CEs confirmed by the cardiac advisory board.
RESULTS: The safety analysis population consisted of 4769 patients. With 74 months of median follow-up, CEs were observed in 159 patients (3.3%): 83 (3.5%) in P + T and 76 (3.2%) in T arms, respectively. Most CEs occurred during anti-HER2 therapy (123; 77.4%) and were asymptomatic or mildly symptomatic decreases in LVEF (133; 83.6%). There were two cardiac deaths in each arm (0.1%). Cardiac risk factors indicated were age > 65 years, body mass index ≥ 25 kg/m2, baseline LVEF between 55% and <60%, and use of an anthracycline-containing chemotherapy regimen. Acute recovery from a CE based on subsequent LVEF values was observed in 127/155 patients (81.9%).
CONCLUSIONS: Dual blockade with P + T does not increase the risk of CEs compared with T alone. The use of anthracycline-based chemotherapy increases the risk of a CE; hence, non-anthracycline chemotherapy may be considered, particularly in patients with cardiovascular risk factors.
Disciplines :
Oncology
Author, co-author :
de Azambuja, E; Institut Jules Bordet and L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium. Electronic address: evandro.azambuja@bordet.be
Agostinetto, E; Institut Jules Bordet and L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium
Procter, M; Frontier Science, Kincraig, Kingussie, UK
Pondé, N; Clinical Oncology Department, AC Camargo Cancer Center, São Paulo, Brazil
Guillaume, S; Institut Jules Bordet and L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium
Parlier, D; Institut Jules Bordet and L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium
Lambertini, M; Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy, Department of Internal Medicine and Medical Sciences (DiMI), School of Medicine, University of Genova, Genova, Italy
Desmet, A; Institut Jules Bordet and L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium
Caballero, C; Breast International Group, Brussels, Belgium
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