Prevention of Ventricular Remodeling in HER2-positive Breast Cancer Treated With Trastuzumab
Angiotensin-converting enzyme inhibitors and beta-blockers do not prevent ventricular remodeling.
Angiotensin-converting enzyme inhibitors (ACEis) and beta-blockers (BBs) do not prevent ventricular remodeling, an important early feature of heart failure for patients with HER2-positive breast cancer receiving trastuzumab, according to a study published in the Journal of Clinical Oncology.1
Heart failure occurs in up to 4% of HER2-positive patients receiving trastuzumab. ACEis and BBs are used to treat heart failure and cancer therapy-related cardiac dysfunction; for this MANTICORE 101-Breast (ClinicalTrials.gov Identifier: NCT01016886) study, researchers evaluated whether these drugs safely prevent trastuzumab-related cardiotoxicity.
The study's primary outcome was cardiac remodeling determined by cardiac MRI; the secondary outcome was change in left ventricular ejection fraction (LVEF), also determined by cardiac MRI. Measurements were taken before and after trastuzumab therapy.
Ninety-nine patients were randomly assigned to receive placebo (32 patients), perindopril (an ACEi, 34 patients), or bisoprolol (a BB, 33 patients).
Neither perindopril nor bisoprolol met the primary outcome of preventing ventricular modeling; the drugs did, however, mitigate the trastuzumab-related reduction in LVEF. The authors noted that the latter effect does “not seem to be mediated via favorable effects on cardiac geometry.”
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Bisoprolol may, furthermore, improve cardiac metabolism, though this effect is not well-understood.Although these drugs were well-tolerated by patients, according to the study's authors, ACEis and BBs do not prevent ventricular remodeling in this patient setting.
- Pituskin E, Mackey JR, Koshman S, et al. Multidisciplinary approach to novel therapies in cardio-oncology research (MANTICORE 101–Breast): a randomized trial for the prevention of trastuzumab-associated cardiotoxicity. J Clin Oncol. 2016 Nov 28. doi: 10.1200/JCO.2016.68.7830 [Epub ahead of print]