Preventing Trastuzumab-Induced Cardiotoxicity in Breast Cancer: Lisinopril or Carvedilol?
Posted: Friday, August 13, 2021
In patients with HER2-overexpressing early-stage breast cancer, a trastuzumab-associated decline in the left ventricular ejection fraction and clinical heart failure often prompt interruption and discontinuation of treatment. Pamela N. Munster, MD, of the University of California San Francisco, and colleagues conducted a study to assess the preventive impact of the angiotensin-converting enzyme inhibitor lisinopril or the beta-blocker carvedilol on the left ventricular ejection fraction during treatment with trastuzumab and chemotherapy. Their results were presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 509).
“The trastuzumab-anthracycline–induced decline in left ventricular ejection fraction could be prevented with concurrent treatment with lisinopril,” the investigators remarked. “[Lisinopril] was tolerable even in patients without hypertension.”
A total of 468 women undergoing chemotherapy with trastuzumab were randomly assigned to receive lisinopril (10 mg), carvedilol (10 mg), or a placebo. Patients were further stratified by whether they were treated with (40%) or without (60%) an anthracycline.
During trastuzumab therapy, a small, not clinically relevant decrease in the left ventricular ejection fraction was observed in all patients; this did not seem to be significantly altered by any of the cardiac interventions. Patients treated with an anthracycline experienced a higher rate of left ventricular ejection fraction decline to less than 50% (21.0% vs. 4.1%).
Compared with the placebo, lisinopril seemed to avert the decline in the left ventricular ejection fraction in those who received an anthracycline (10.8% vs. 30.5%; P = .045). A smaller effect was observed with carvedilol, but it did not seem to be statistically significant. The incidence rate of cardiotoxicity manifesting as left ventricular ejection fraction decrease by at least 10% within the normal range seemed to be similar between patients who were treated with and without an anthracycline; it was not found to be affected by treatment with either lisinopril or carvedilol.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
