ASCO Annual Meeting

ASCO Annual Meeting

Perspective from Fatima Cardoso, MD
Source:

Munster PN, et al. Abstract 509. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.

Disclosures: Munster reports leadership roles with Alessa Therapeutics and EpiAxis Therapeutics; stock ownership in Alessa Therapeutics, AtlasMedx and OnKure; consultant/advisory roles with Array BioPharma, AstraZeneca, Athenex, AtlasMedx, BeiGene, Bristol Myers Squibb, GenomeSmart, IQVIA, Jubilant Pharmaceuticals, NeoHealth and RasCal Therapeutics; and honoraria or research funding paid to her institution from 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. She also reports a University of California, San Francisco patent on using silastic implants to deliver anticancer agents. The other researchers report no relevant financial disclosures.
June 06, 2021
2 min read
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Lisinopril may prevent cardiotoxicity of anthracycline, trastuzumab use in breast cancer

Perspective from Fatima Cardoso, MD
Source:

Munster PN, et al. Abstract 509. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.

Disclosures: Munster reports leadership roles with Alessa Therapeutics and EpiAxis Therapeutics; stock ownership in Alessa Therapeutics, AtlasMedx and OnKure; consultant/advisory roles with Array BioPharma, AstraZeneca, Athenex, AtlasMedx, BeiGene, Bristol Myers Squibb, GenomeSmart, IQVIA, Jubilant Pharmaceuticals, NeoHealth and RasCal Therapeutics; and honoraria or research funding paid to her institution from 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. She also reports a University of California, San Francisco patent on using silastic implants to deliver anticancer agents. The other researchers report no relevant financial disclosures.
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A decrease in left ventricular ejection fraction to below normal levels occurred more frequently among women with HER2-positive early-stage breast cancer who received anthracyclines prior to trastuzumab, according to study results.

The findings of the prospective randomized study, presented at the virtual ASCO Annual Meeting, showed this decline in left ventricular ejection fraction (LVEF) appeared preventable with concurrent lisinopril.

A decrease in left ventricular ejection fraction to below normal levels occurred more frequently among women with HER2-positive early-stage breast cancer who received anthracyclines prior to trastuzumab.
Data were derived from Munster PN, et al. Abstract 509. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.

“It would appear that anthracyclines have a more profound negative effect, even in a younger group of women, that we should take in consideration and we may be able to offer an intervention for those who will benefit from or need an anthracycline,” Pamela N. Munster, MD, professor in the department of medicine (hematology/oncology) at University of California, San Francisco, and director of the early-phase clinical trials unit, co-leader of the Center for BRCA Research and co-leader of the molecular oncology program at UCSF Helen Diller Family Comprehensive Cancer Center, told Healio.

Although trastuzumab (Herceptin, Genentech) is an effective treatment for HER2-positive breast cancer, it is associated with a decline in LVEF and clinical heart failure, leading to treatment interruption and discontinuation, according to study background.

Thus, Munster and colleagues sought to evaluate the impact of using an ACE inhibitor or beta blocker to prevent LVEF in this patient population.

Pamela N. Munster, MD
Pamela N. Munster

“Patients in the community often have less access to more comprehensive care and we wanted to both determine the risks on the heart and whether a simple intervention could be meaningful,” Munster said.

The analysis included data of 468 women (mean age, 51 ± 10.7 years) with HER2-overexpressing early-stage breast cancer who received treatment at one of 127 community-based oncology practices. Of them, 189 received an anthracycline prior to trastuzumab, and 279 received trastuzumab alone.

Mean LVEF at baseline was 62.6%, mean BMI was 28.4 kg/m2, and 8.4% of the population had hypertension.

Researchers randomly assigned patients to receive 10 mg lisinopril, an ACE inhibitor; 10 mg carvedilol, a beta blocker; or placebo, starting on day 1 with trastuzumab for 1 year. Outcome measures assessed every 12 weeks included a decline in LVEF to below normal levels, defined as lower than 50%, or a 10% or greater decrease in LVEF that remained at normal levels.

At 12 months, a greater proportion of women treated with an anthracycline experienced a drop in LVEF to below normal levels than those treated with trastuzumab alone (21% vs. 4.1%).

In the group that received an anthracycline, significantly fewer women who received lisinopril than placebo experienced LVEF below 50% (10.8% vs. 30.5%; P = .045), but the 22.8% rate with carvedilol did not represent a significant difference from that of placebo.

“The findings of this study suggest that the drop in LVEF to below 50% was much larger than previously reported in the anthracycline group,” Munster said during her presentation.

In the group treated with trastuzumab alone, researchers observed no significant differences in those who showed LVEF below normal levels whether they received carvedilol (4.5%), lisinopril (1.3%) or placebo (6.4%).

An LVEF drop of 10% or greater at 12 months occurred among 14.4% of the trastuzumab-alone group and 5.5% of the anthracycline-trastuzumab group, with neither lisinopril nor carvedilol significantly affecting this manifestation of cardiotoxicity.

“Most importantly, we found a baseline elevated blood pressure in many of our patients,” Munster told Healio. “Maximizing overall health care including treating elevated blood pressure is important for overall cardiac health. Lisinopril is well-tolerated and we could have probably given a lower dose. The side effects of lisinopril are minimal compared with the benefits we saw, and this should be considered.

“In a curative breast cancer setting, preserving cardiac health is important and underlying risks factors should be addressed,” Munster added. “Breast cancer treatment should include maximized preservation of all health parameters.”

Future research should address how stress, environment, lack of exercise and obesity affect breast cancer treatment, Munster said.