Lisinopril may prevent cardiotoxicity from the use of anthracyclines and trastuzumab in breast cancer
Source / Disclosures
Munster PN, et al. Abstract 509. Presented to: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.
Munster reports leadership roles with Alessa Therapeutics and EpiAxis Therapeutics; shareholding in Alessa Therapeutics, AtlasMedx and OnKure; consultant / consultant roles at Array BioPharma, AstraZeneca, Athenex, AtlasMedx, BeiGene, Bristol Myers Squibb, GenomeSmart, IQVIA, Jubilant Pharmaceuticals, NeoHealth and RasCal Therapeutics; and research fees or funding paid to its institution by Andes Biotechnologies, BioMarin Pharmaceutical, Bristol Myers Squibb, Celgene, CStone Pharmaceuticals, Epigene Labs, Genentech / Roche, GlaxoSmithKline, Immune Design, Intellikine, Merck, Merrimack, Nektar, Novartis, OncoMed, Onconova Therapeutics, OncoSec Medical, Pfizer, Piramal Life Science, Plexxikon, Prometheus and Sanofi. It also reports a patent from the University of California, San Francisco on the use of silastic implants to deliver anticancer agents. The other researchers do not report any relevant financial disclosures.
According to the results of the study, a decrease in left ventricular ejection fraction to below normal levels occurred more frequently in women with early-stage HER2-positive breast cancer who had received anthracyclines before trastuzumab.
The results of the prospective randomized study, presented at the ASCO virtual annual meeting, showed that this drop in left ventricular ejection fraction (LVEF) appeared to be preventable with concomitant lisinopril.
“It would appear that the anthracyclines have a more profound negative effect, even in a group of younger women, which we should consider and we may be able to offer an intervention to those who will benefit or need an anthracycline. “, Pamela NOT. Munster, MD, Professor in the Department of Medicine (Hematology / Oncology) and at the University of California, San Francisco, and Director of the Early Phase Clinical Trials Unit, co-leader of the Center for BRCA Research and co-lead of the molecular oncology program at UCSF Helen Diller Family Comprehensive Cancer Center, said Healio.
Although trastuzumab (Herceptin, Genentech) is an effective treatment for HER2-positive breast cancer, it is associated with a drop in LVEF and clinical heart failure, leading to interruption and discontinuation of treatment, according to the context of the study.
Thus, Munster and colleagues sought to assess the impact of using an ACE inhibitor or beta blocker to prevent LVEF in this patient population.
Pamela N. Munster
“Patients in the community often have less access to more comprehensive care and we wanted to both determine the risks to the heart and whether a simple intervention could be meaningful,” Munster said.
The analysis included data from 468 women (mean age, 51 ± 10.7 years) with early stage breast cancer overexpressing HER2 who received treatment at one of 127 community oncology practices. Of these, 189 received an anthracycline before trastuzumab and 279 received trastuzumab alone.
The mean baseline LVEF was 62.6%, the mean BMI was 28.4 kg / m2, and 8.4% of the population suffered from hypertension.
The researchers randomly assigned patients to 10 mg of lisinopril, an ACE inhibitor; 10 mg of carvedilol, a beta-blocker; or placebo, starting on day 1 with trastuzumab for 1 year. Outcome measures evaluated every 12 weeks included a decrease in LVEF below normal levels, defined as less than 50%, or a decrease of 10% or more in LVEF that remained at normal levels.
At 12 months, a greater proportion of women treated with an anthracycline had a decrease in LVEF to below normal levels than those treated with trastuzumab alone (21% vs. 4.1%).
In the anthracycline group, significantly fewer women who received lisinopril than placebo had LVEF less than 50% (10.8% vs. 30.5%; P = 0.045), but the level of 22.8% with carvedilol did not represent a significant difference compared to placebo.
“The results of this study suggest that the decrease in LVEF to less than 50% was much greater than that previously reported in the anthracycline group,” Munster said during his presentation.
In the group treated with trastuzumab alone, the researchers observed no significant difference in those with lower-than-normal LVEF, whether they received carvedilol (4.5%), lisinopril (1.3%) or a placebo (6.4%).
A decrease in LVEF of 10% or more at 12 months occurred in 14.4% of the trastuzumab alone group and 5.5% of the anthracycline-trastuzumab group, without lisinopril or carvedilol significantly affecting this manifestation of cardiotoxicity.
“More importantly, we have found baseline high blood pressure in a lot of our patients,” Munster told Healio. “Maximizing general health care, including the treatment of high blood pressure, is important for overall heart health. Lisinopril is well tolerated and we probably could have given a lower dose. The side effects of lisinopril are minimal compared to the benefits we’ve seen, and this should be taken into account.
“In a breast cancer cure setting, preserving heart health is important and the underlying risk factors must be taken into account,” Munster added. “Treatment for breast cancer should include maximum preservation of all health parameters. “
Future research should examine how stress, the environment, lack of exercise and obesity affect breast cancer treatment, Munster said.