No Significant Benefit of Perindopril or Bisoprolol in Reducing Trastuzumab-Associated Cardiac Remodeling in HER2-Positive Breast Cancer
Use of the angiotensin-converting enzyme inhibitor perindopril or the beta-blocker bisoprolol did not reduce the risk of trastuzumab (Herceptin)-related cardiac remodeling in women with HER2-positive early breast cancer, according to a Canadian trial reported by Pituskin et al in the Journal of Clinical Oncology. Both agents reduced trastuzumab-related declines in left-ventricular ejection fraction.
Study Details
In this double-blind trial, 94 patients receiving adjuvant trastuzumab were randomized 1:1:1 to receive perindopril (n = 33), bisoprolol (n = 31), or placebo (n = 30). Perindopril at 2 mg daily, bisoprolol at 2.5 mg daily, or dose level 1 placebo were started within 7 days before the start of trastuzumab and titrated weekly as tolerated over 3 weeks; daily target doses were perindopril at 8 mg, bisoprolol at 10 mg, and dose level 3 placebo.
Patients underwent cardiac magnetic resonance imaging at baseline and after trastuzumab cycle 17 (approximately 52 weeks) to assess left-ventricular volumes and left-ventricular ejection fraction. The primary outcome measure was cardiac remodeling, defined as the change in indexed left-ventricular end diastolic volume.
Outcomes
The study drugs were well tolerated, with no serious adverse events being observed.
After 17 cycles of trastuzumab, the indexed left-ventricular end diastolic volume was increased in perindopril patients by 7 ± 14 mL/m2, in bisoprolol patients by 8 mL ± 9 mL/m2, and in placebo patients by 4 ± 11 mL/m2 (P = .36). Trastuzumab-related decline in left-ventricular ejection fraction was reduced with bisoprolol (–1 ± 5%) compared with perindopril (–3 ± 4%) and placebo (–5 ± 5%; P = .001).
On multivariate analysis, declines in left-ventricular ejection fraction were predicted by baseline left-ventricular ejection fraction and reduced with the use of perindopril (P = .016) and bisoprolol (P < .001).
The investigators concluded: “Perindopril and bisoprolol were well tolerated in patients with HER2-positive early breast cancer who received trastuzumab and protected against cancer therapy–related declines in [left-ventricular ejection fraction]; however, trastuzumab-mediated left ventricular remodeling—the primary outcome—was not prevented by these pharmacotherapies.”
The study was supported by the Canadian Institutes of Health Research, the Alberta Cancer Foundation, and the University Hospital Foundation.
D. Ian Paterson, MD, of the University of Alberta, Edmonton, Canada, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
