Long-term cardiac outcomes of patients with HER2-positive breast cancer treated in the adjuvant lapatinib and/or trastuzumab Treatment Optimization Trial

Daniel Eiger, Noam F. Pondé, Dominique Agbor-Tarh, Alvaro Moreno-Aspitia, Martine Piccart, Florentine S. Hilbers, Olena Werner, Saranya Chumsri, Amylou Dueck, Judith R. Kroep, Henry Gomez, István Láng, Richard J Rodeheffer, Michael S. Ewer, Thomas Suter, Evandro de Azambuja

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1453-1460
Number of pages8
JournalBritish journal of cancer
Volume122
Issue number10
DOIs
StatePublished - May 12 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Eiger, D., Pondé, N. F., Agbor-Tarh, D., Moreno-Aspitia, A., Piccart, M., Hilbers, F. S., Werner, O., Chumsri, S., Dueck, A., Kroep, J. R., Gomez, H., Láng, I., Rodeheffer, R. J., Ewer, M. S., Suter, T., & de Azambuja, E. (2020). Long-term cardiac outcomes of patients with HER2-positive breast cancer treated in the adjuvant lapatinib and/or trastuzumab Treatment Optimization Trial. British journal of cancer, 122(10), 1453-1460. https://doi.org/10.1038/s41416-020-0786-x