By Marilynn Larkin
NEW YORK (Reuters Health) - 5/6/2019
ACE inhibitors or beta blockers can preserve cardiac function and avoid chemotherapy disruption in HER2-positive breast cancer patients treated with anthracyclines followed by trastuzumab, researchers say.
"The two most powerful drugs for aggressive HER2-positive breast cancer - anthracyclines and trastuzumab - are known for their ability to weaken cardiac muscle, causing cardiomyopathy that may lead to heart failure," Dr. Maya Guglin of the University of Kentucky in Lexington told Reuters Health. "Our most important finding is that patients on trastuzumab respond differently to pharmacologic prevention of cardiotoxicity based on prior treatment with anthracyclines."
"There was a significant reduction in cardiotoxicity for patients on carvedilol or lisinopril who received doxorubicin before trastuzumab," she said by email. "Also, being on either carvedilol or lisinopril decreased the number of interruptions in trastuzumab in the whole study population."
"These data are the crucial first step towards establishing a new standard of care to reduce the risk of cardiotoxicity for patients undergoing treatment for HER2-positive breast cancer," she said.
In a double-blind, placebo-controlled trial, Dr. Guglin and colleagues studied HER2-positive breast cancer treated with trastuzumab for 12 months and followed for two years. Participants were stratified by anthracycline use and then randomized to receive lisinopril, carvedilol, or placebo.
As reported online June 3 in the Journal of the American College of Cardiology, 468 women (mean age, 51) were included in the study. Cardiotoxicity was comparable in the three arms and occurred in 32% of those taking placebo, 29% on carvedilol, and 30% on lisinopril.
However, for patients who received anthracyclines, event rates were higher in the placebo (47%) versus the lisinopril (37%) and the carvedilol (31%) groups. Further, cardiotoxicity-free survival was longer on both carvedilol (hazard ratio, 0.49) and lisinopril (HR, 0.53) compared to placebo.
In the whole cohort, as well as in the anthracycline arm, patients on active therapy with either angiotensin converting enzyme inhibitors or beta-blockers had fewer trastuzumab treatment interruptions than those on placebo.
"In cases of particularly aggressive breast cancer - about one-third of all cases - oncologists can now more confidently prescribe anthracycline when indicated and give either lisinopril or carvedilol to decrease the risk of cardiomyopathy, avoiding many unnecessary treatment interruptions, reducing patients' anxiety, and improving prognosis," Dr Guglin said. "Also, our trial may lead to a change in current practice and result in a different approach to patients with breast cancer based on their prior exposure to anthracyclines."
Dr. Ana Barac of the Medstar Washington Hospital Center in Washington, DC, coauthor of a related editorial, commented by email, "As a result of this and several similar recent studies, I believe that more oncologists will consider using beta-blockers and angiotensin-cardioverting enzyme inhibitors at the initiation of cancer treatment with high cardiovascular risk."
That said, she told Reuters Health, "The study is limited by the lack of rigorous cardiac imaging analysis that is recommended in contemporary clinical studies, in particular when their primary outcome relies on cardiac imaging. This might be the reason for the higher incidence of cardiac dysfunction in this trial than was previously reported."
"We also do not know how long to treat, whether to increase the dose and whether other agents could have the same effect," she noted.
"Both in tertiary institutions and in community centers, the worlds of cardiology and oncology tend to be separate with minimal overlap. That makes the design and the execution of cardio-oncology trials very difficult," she acknowledged. "But we should not settle for less, as the only way to advance patient care is through improved understanding of both cardiovascular and oncology benefits and risks."
"Partnerships at the level of professional societies, regulatory and funding agencies and advocacy will be critical to make high impact cardio-oncology trials a reality," Dr. Barac concluded.
J Am Coll Cardiol 2019.