Adding trastuzumab to anthracycline and taxane-based chemotherapy does not result in worsening of long-term cardiac outcomes in patients with node-positive, HER2-positive early breast cancer, according to a new study.
The NSABP Protocol B-31 trial showed that adding trastuzumab to paclitaxel following doxorubicin and cyclophosphamide improved overall survival. With 7 years of follow-up, the incidence of severe cardiac events was increased in the trastuzumab group. “However, severe cardiotoxicity seemed to be an early event, because only two cases of congestive heart failure occurred > 2 years after initiation of trastuzumab,” wrote study authors led by Edward H. Romond, MD, of the University of Kentucky in Lexington.
Little is known about the cardiac effects over a longer time period. The new analysis assessed those longer-term cardiac results in 407 patients (110 control patients, 297 trastuzumab patients) from the B-31 trial; patients were included if they were alive and disease free. The results were published online ahead of print in the Journal of Clinical Oncology.
The mean age of included patients was 48.3 years, and the median follow-up for this analysis was 8.8 years. At 18 months, the mean decline from baseline in left-ventricular ejection fraction (LVEF) was 3.2% in the control patients and 3.9% with trastuzumab. At the long-term follow-up assessment, the mean decline was 3.9% in the control group and 2.8% in the trastuzumab group.
At that long-term follow-up assessment, five of the control patients (4.5%) had an LVEF decline of at least 10% and less than 50%; 10 trastuzumab patients (3.4%) met this mark. There were only three patients—one control, two trastuzumab—who had declines above 50% at 18 months and less than 40% at the long-term assessment.
Similar proportions of the groups were receiving antihypertensive therapy at the long-term assessment—31.8% of control patients and 33.3% of trastuzumab patients.
At a previous report, 37 trastuzumab patients had experienced a cardiac event, including one cardiac death. Only 23 of those were eligible for the long-term analysis, and eight of those consented to participate. Ten of the 37 patients have died.
Lower scores on the Duke Activity Status Index were correlated with several factors, including age, baseline hypertensive medication use, and baseline hyperlipidemia medication use, but there was no such correlation with trastuzumab use.
The authors noted that this is limited by its failure to include all participants in the B-31 trial, though those who did participate had similar baseline characteristics to the full cohort.
“Our report provides encouraging data from the B-31 study and indicates that in breast cancer survivors without a pre-existing cardiac history, the addition of trastuzumab to adjuvant anthracycline-based chemotherapy does not result in long-term worsening of cardiac function, cardiac symptoms, or health-related quality of life,” they concluded.