Is Cardiac Prophylaxis Effective in Early HER2+ Breast Cancer Patients?

In patients with HER2-positive breast cancer treated with anthracyclines as well as trastuzumab, the addition of lisinopril or carvedilol can reduce the risk of cardiotoxicity, according to a new study.

“Trastuzumab is a highly effective therapy for HER2-positive breast cancer,” said Pamela N. Munster, MD, of the University of California, San Francisco. “However, cardiac side effects require frequent monitoring, resulting in dose interruptions and discontinuation.” She presented these results of a randomized trial in patients with early HER2-positive breast cancer at the San Antonio Breast Cancer Symposium (SABCS), held December 4–8 (abstract GS5-01).

A total of 468 patients were randomized to receive lisinopril, carvedilol, or placebo; they were stratified based on whether or not they received anthracycline treatment. Of those, 193 patients came off the therapy before a 52-week treatment period was completed. Baseline characteristics of patients were generally similar, though those who received anthracyclines were younger (48 years vs 53 years at baseline) and had lower blood pressure.

In the full cohort, cardiotoxicity-defined as a greater than 10% decrease in left ventricular ejection fraction (LVEF), or a drop larger than 5% in those with LVEF below 50%-was reported at similar rates across the placebo (32%), lisinopril (30%), and carvedilol (29%) groups. Compared with placebo, lisinopril yielded a hazard ratio (HR) for cardiotoxicity of 0.74 (95% CI, 0.48–1.12; P = .076); for carvedilol, the HR was 0.71 (95% CI, 0.47–1.07; P = .052).

When separated based on anthracycline treatment, though, the therapies did offer benefit. In just those who received anthracyclines, the HR for cardiotoxicity with lisinopril was 0.53 (95% CI, 0.30–0.94; P = .015). For carvedilol, the HR was 0.49 (95% CI, 0.27–0.89; P = .009).

Munster said the drugs were well tolerated, with virtually no grade 3 toxicity associated with lisinopril or carvedilol. There was more fatigue, dizziness, cough, and hypertension with lisinopril than with carvedilol.

“In patients with HER2-positive breast cancer treated with trastuzumab, should you choose to use an anthracycline, the addition of lisinopril or carvedilol should be considered,” Munster concluded.

Jennifer Ligibel, MD, of Dana-Farber Cancer Institute in Boston, was the discussant for the study, and she said the study was well designed and is the largest trial to date looking at this sort of prevention in HER2-positive patients. She also noted that the results in those receiving taxanes rather than anthracyclines are reassuring, given that cardiotoxicity does not appear to be a significant risk.

In the anthracycline group, though, she wondered “whether we want to be adding a new medication for a change in echocardiogram without clinical congestive heart failure.” The study did not include women with baseline cardiac risk factors, and though there was clearly a benefit with lisinopril and carvedilol, further research may still be needed. “I think we need a bit more information in order to be routinely prescribing these medications,” Ligibel said.