Abstract GS5-01: 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

Background: Exposure to trastuzumab for one year is an integral part of therapy for patients with early stage HER2-positive breast cancer. Yet, cardiac side effects, particularly in patients who also receive anthracyclines require frequent monitoring and result in dose interruptions and discontinuation of trastuzumab. Prophylactic use of angiotensin converting enzyme (ACE) nhibitors or beta blockers (BB) may prevent cardiotoxicity associated with chemotherapy and trastuzumab. Methods A large community-based prospective double-blind, placebo-controlled trial, evaluated the rates of pre-specified cardiotoxicity in patients with early stage breast cancer treated with one year of trastuzumab. Cardiac events were followed for two years. Patients were randomized to simultaneously receive either the ACE inhibitor, lisinopril, or the BB, carvedilol, or placebo and were further stratified by anthracycline use to determine whether ACE inhibitors or BB can prevent trastuzumab-induced decrease in left ventricular ejection fraction (LVEF) and trastuzumab interruptions. Results: The study included 468 eligible patients (median age:51, BMI:27 kg/m 2 , baseline systolic BP: 126mmHg and LVEF :63 ± 6.29%) from 127 community-based practices, 189 patients received an anthracycline. For the entire study population and the non-anthracycline group, no difference in number of trastuzumab interruptions were seen. For patients receiving an anthracycline, cardiac event rates were higher in the placebo group (47%), and reduced in both the lisinopril (37%), and the carvedilol (31%) groups. Interruptions of trastuzumab were required in 23% patients on lisinopril and 20% on carvedilol compared to 40% on placebo (p=0.007). Changes in LVEF from baseline (least square means, SE) were significantly reduced with both carvedilol (-4.5 (0.8), p=0.008, and lisinopril (-4.0 (0.8), p=0.002) than placebo, (-7.7 (0.8). Cardiotoxicity-free survival was longer on both carvedilol (hazard ratio 0.49, 95% confidence intervals 0.27, 0.89, p=0.009) or lisinopril (HR 0.53, CI 0.30, 0.94, p=0.015). Conclusions In patients with HER2-positive breast cancer receiving trastuzumab and an anthracycline, both lisinopril and carvedilol during treatment reduced cardiotoxicity in patients, but not in those with non-anthracyline containing regimens. 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. Citation Format: Munster P, Krischer J, Tamura R, Fink A, Bello-Matricaria L, Guilin M. 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 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS5-01.