Perindopril, Bisoprolol Not Effective for Preventing Trastuzumab-mediated Left Ventricular Remodeling

Perindopril, an angiotensin-converting enzyme inhibitor, and the beta blocker bisoprolol protected against trastuzumab-related declines.
Perindopril, an angiotensin-converting enzyme inhibitor, and the beta blocker bisoprolol protected against trastuzumab-related declines.

Perindopril, an angiotensin-converting enzyme (ACE) inhibitor, and the beta blocker bisoprolol protected against trastuzumab-related declines in left ventricular ejection fraction (LVEF) but did not prevent therapy-mediated left ventricular remodeling, a study published in the Journal of Clinical Oncology has shown.1

Adding trastuzumab to adjuvant regimens for the treatment of HER2-positive early breast cancer has significantly improved patient outcomes; however, dose-independent left ventricular dysfunction has been reported in up to 18% of cases and overt heart failure in up to 4%. Current guidelines recommend cardiac MRI as the gold standard for detecting cancer therapy-related cardiac dysfunction.

Because ACE inhibitors and beta blockers are internationally recommended as initial treatment of heart failure and established cancer therapy-related cardiac dysfunction, researchers sought to evaluate whether they could be used to prevent trastuzumab-related cardiotoxicity.

For the double-blind, phase 1/2 study (ClinicalTrials.gov Identifier: NCT01016886), researchers enrolled 94 patients with HER2-positive early breast cancer and randomly assigned them 1:1:1 to receive perindopril, bisoprolol, or placebo for the duration of trastuzumab adjuvant therapy.

Patients underwent cardiac MRI at baseline and after cycle 17 of treatment for the determination of left ventricular volumes and LVEF. Researchers evaluated cardiotoxicity as the change in indexed left ventricular end diastolic volume and LVEF.

Results showed that indexed left ventricular end diastolic volume increased in all 3 groups (P =.36). Investigators found that trastuzumab-mediated decline in LVEF was minimized in patients treated with bisoprolol compared with patients who had perindopril and those with placebo (P =.001); however, neither the ACE inhibitor nor the beta blocker attenuated trastuzumab-mediated left ventricular modeling, the primary outcome measure.

Reference

1. 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]
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