Removing anthracyclines from HER2-positive breast cancer treatment reduces cardiac toxicity

When an anthracycline is not used concomitantly with adjuvant trastuzumab to treat HER2-positive breast cancer, cardiac toxicity is reduced, according to a multinational randomized controlled trial published in the October 6, 2011, New England Journal of Medicine.

"Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity," the researchers emphasized. They continued, "We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab."

To achieve their objective, researchers from the Breast Cancer International Research Group randomly assigned 3,222 women with invasive, high-risk, node-negative or node-positive, HER2-positive adenocarcinoma, to receive a standard anthracycline (specifically doxorubicin)–taxane chemotherapy regimen (AC-T), the identical regimen plus adjuvant trastuzumab, or a new nonanthracycline, trastuzumab-based regimen (TCH). To evaluate the cardiac toxicity of the regimens, they put in place a safety evaluation protocol that included monitoring left ventricular ejection fraction (LVEF) a total of 7 times throughout the study.

No cases of cardiac death were observed in any of the treatment groups.

Also of importance, researchers did not find a significant difference in the rate of disease-free or overall survival between the 2 trastuzumab-containing regimens, and the rate of many acute toxic effects and leukemia were also lower in the TCH group. Consequently, the researchers concluded their report by remarking, "The risk-benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia."

SOURCE

Slamon D, Eiermann W, Robert N, et al. for the Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365:1273–1283.