Lisinopril and Carvedilol May Reduce Cardiotoxicity During Adjuvant Trastuzumab Treatment

In a randomized, double-blind, placebo-controlled, multicenter trial, lisinopril, an angiotensin converting enzyme or ACE inhibitor, and carvedilol, a beta blocker, reduced cardiotoxicity among patients with early stage HER2-positive breast cancer during adjuvant trastuzumab, but only for those receiving an anthracycline. The results were presented at the 2018 San Antonio Breast Cancer Symposium (SABCS) in Texas.¹

A total of 468 patients with early-stage, HER2-positive breast cancer who were receiving adjuvant trastuzumab were enrolled from 127 community-based practices. Patients were randomly assigned to receive placebo, lisinopril, or carvedilol throughout 1 year of adjuvant trastuzumab. The primary endpoints were rates of cardiotoxicity during the 1 year of adjuvant trastuzumab and in the year after. Cardiotoxicity was defined as an absolute decrease in left ventricular ejection fraction (LVEF) of 10% or at least a 5% decrease for LVEF less than 50%.

Patient outcomes were stratified by anthracycline use; 189 patients were in the anthracycline cohort and 279 were in the non-anthracycline cohort. Patients in the anthracycline cohort were on average younger (48 years vs 53 years) and had lower systolic blood pressure (120 mmHg vs 130 mmHg) than what was reported in the non-anthracycline cohort. No difference in number of trastuzumab interruptions were observed between the anthracycline cohort and non-anthracycline cohort.

Cardiotoxicity was similar across treatment groups: 32% in placebo, 29% in carvedilol, and 30% in lisinopril; cardiotoxicity-free survival was also similar.  However, in the anthracycline cohort, cardiotoxicity-free survival was longer for carvedilol (HR = 0.49, 95% CI, 0.27 – 0.89, P = .009), and lisinopril (HR 0.53, 95% CI, 0.30 – 0.94, P= 0.015) compared with placebo.

“The use of lisinopril or carvedilol may allow the use of an anthracycline without compromising trastuzumab treatment in those who might benefit from an anthracycline,” the authors concluded.

Read more of Cancer Therapy Advisor‘s coverage of the SABCS 2018 meeting by visiting the conference page.

Reference

1. Munster P, Krischer J, Tamura R, et al. A randomized community-based trial of an angiotensin converting enzyme inhibitor, lisinopril or a beta blocker, carvedilol for the prevention of cardiotoxicity in patients with early stage HER2-positive breast cancer receiving adjuvant trastuzumab. Oral presentation at: 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, TX. Abstract GS5-01.