Journal article
Long-term cardiac outcomes of patients with HER2-positive breast cancer treated in the adjuvant lapatinib and/or trastuzumab Treatment Optimization Trial.
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Eiger D
Institut Jules Bordet Institute and L'Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
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Pondé NF
Institut Jules Bordet Institute and L'Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
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Agbor-Tarh D
Frontier Science, Kingussie, United Kingdom.
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Moreno-Aspitia A
Mayo Clinic, Jacksonville, FL, USA.
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Piccart M
Institut Jules Bordet Institute and L'Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
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Hilbers FS
Breast International Group (BIG), Brussels, Belgium.
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Werner O
Novartis Pharma AG, Basel, Switzerland.
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Chumsri S
Mayo Clinic, Jacksonville, FL, USA.
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Dueck A
Alliance Statistics and Data Center, Mayo Clinic, Scottsdale, AZ, USA.
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Kroep JR
Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
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Gomez H
Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
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Láng I
Istenhegyi Géndiagnosztika Private Health Center, Oncology Clinic, Budapest, Hungary.
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Rodeheffer RJ
Cardiovascular Department, Mayo Clinic, Rochester, MN, USA.
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Ewer MS
MD Anderson Cancer Center, Houston, TX, USA.
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Suter T
Department of Cardiology, lnselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
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de Azambuja E
Institut Jules Bordet Institute and L'Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. evandro.azambuja@bordet.be.
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Published in:
- British journal of cancer. - 2020
English
BACKGROUND
Cardiotoxicity is the most significant adverse event associated with trastuzumab (T), the main component of HER2-positive breast cancer (BC) treatment. Less is known about the cardiotoxicity of dual HER2 blockade with T plus lapatinib (L), although this regimen is used in the metastatic setting.
METHODS
This is a sub-analysis of the ALTTO trial comparing adjuvant treatment options for patients with early HER2-positive BC. Patients randomised to either T or concomitant T + L were eligible. Cardiac events (CEs) rates were compared according to treatment arm.
RESULTS
With 6.9 years of median follow-up (FU) and 4190 patients, CE were observed in 363 (8.6%): 166 (7.9%) of patient in T + L arm vs. 197 (9.3%) in T arm (OR = 0.85 [95% CI, 0.68-1.05]). During anti-HER2 treatment 270 CE (6.4%) occurred while 93 (2.2%) were during FU (median time to onset = 6.6 months [IQR = 3.4-11.7]). While 265 CEs were asymptomatic (73%), 94 were symptomatic (26%) and four were cardiac deaths (1%). Recovery was observed in 301 cases (83.8%). Identified cardiac risk factors were: baseline LVEF < 55% (vs > 64%, OR 3.1 [95% CI 1.54-6.25]), diabetes mellitus (OR 1.85 [95% CI 1.25-2.75]), BMI > 30 kg/m2 (vs < 25 mg/kg2, OR 2.21 [95% CI 1.40-3.49]), cumulative dose of doxorubicin ≥240 mg/m2 (OR 1.36 [95% CI 1.01-1.82]) and of epirubicin≥ 480 mg/m2 (OR 2.33 [95% CI 1.55-3.51]).
CONCLUSIONS
Dual HER2 blockade with T + L is a safe regimen from a cardiac perspective, but cardiac-focused history for proper patient selection is crucial.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov Identifier: NCT00490139 (registration date: 22/06/2007); EudraCT Number: 2006-000562-36 (registration date: 04/05/2007); Sponsor Protocol Number: BIG2-06 /EGF106708/N063D.
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Language
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Open access status
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closed
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Identifiers
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Persistent URL
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https://sonar.ch/global/documents/123344
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