Author + information
- Received January 31, 2019
- Revision received February 28, 2019
- Accepted March 3, 2019
- Published online June 3, 2019.
- Maya Guglin, MD, PhDa,∗ (, )@MGuglin,
- Jeffrey Krischer, PhDb,
- Roy Tamura, PhDb,
- Angelina Fink, MPHc,
- Lauren Bello-Matricaria, MPHb,
- Worta McCaskill-Stevens, MDd and
- Pamela N. Munster, MDe
- aUniversity of Kentucky, Gill Heart & Vascular Institute, Lexington, Kentucky
- bUniversity of South Florida, Health Informatics Institute, Tampa, Florida
- cH. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
- dNational Cancer Institute, Community Oncology and Prevention Trials Research Group, Rockville, Maryland
- eUniversity of California San Francisco, San Francisco, California
- ↵∗Address for correspondence:
Dr. Maya Guglin, University of Kentucky, Gill Heart & Vascular Institute, First Floor, Suite G100, 800 Rose Street, Lexington, Kentucky 40536.
Background Trastuzumab is highly effective for human epidermal growth factor receptor type 2 (HER2)–positive breast cancer but is associated with a decline in left ventricular ejection fraction.
Objectives The purpose of this study was to determine whether angiotensin-converting enzyme inhibitors or beta-blockers reduce the rate of trastuzumab-induced cardiotoxicity (left ventricular ejection fraction decrease >10%, or >5% if below 50%) and limit treatment interruptions.
Methods In this double-blind, multicenter, placebo-controlled trial, cardiotoxicity and treatment interruptions in patients with HER2-positive breast cancer treated with trastuzumab for 12 months were evaluated over a 2-year period. Patients were stratified by anthracycline use and then randomized to receive lisinopril, carvedilol, or placebo.
Results The study included 468 women, age 51 ± 10.7 years. For the entire cohort, cardiotoxicity was comparable in the 3 arms and occurred in 32% of patients on placebo, 29% on carvedilol, and 30% on lisinopril. For patients receiving anthracyclines, the event rates were higher in the placebo group (47%) than in the lisinopril (37%) and the carvedilol (31%) groups. Cardiotoxicity-free survival was longer on both carvedilol (hazard ratio: 0.49; 95% confidence interval: 0.27 to 0.89; p = 0.009) and lisinopril (hazard ratio: 0.53; 95% confidence interval: 0.30 to 0.94; p = 0.015) than on placebo. In the whole cohort, as well as in the anthracycline arm, patients on active therapy with either angiotensin-converting enzyme inhibitor or beta-blockers experienced fewer interruptions in trastuzumab than those on placebo.
Conclusions In patients with HER2-positive breast cancer treated with trastuzumab, both lisinopril and carvedilol prevented cardiotoxicity in patients receiving anthracyclines. For such patients, lisinopril or carvedilol should be considered to minimize interruptions of trastuzumab. (Lisinopril or Coreg CR in Reducing Side Effects in Women With Breast Cancer Receiving Trastuzumab; NCT01009918)
The trial was cosponsored by the SunCoast Community Clinical Oncology Programs Research Base at University of South Florida and National Cancer Institute (5U10CA081920-11 U.S. National Institutes of Health Grant/Contract). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received January 31, 2019.
- Revision received February 28, 2019.
- Accepted March 3, 2019.
- 2019 American College of Cardiology Foundation
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