Limited Cardiac Toxicity With Post-Chemo Pertuzumab/Trastuzumab in HER2+ Breast Cancer

A study of the cardiac effects of pertuzumab and trastuzumab following chemotherapy in the neoadjuvant setting for HER2-positive breast cancer patients revealed no new safety signals, and the high response rates and safety profile support the agents’ use.

“Trastuzumab is associated with a risk of cardiac toxicity, particularly when given with anthracyclines,” wrote study authors led by Sandra M. Swain, MD, of Georgetown University Medical Center in Washington, DC. “Cardiac safety within the context of chemotherapy regimen is an important consideration.”

The phase II BERENICE study evaluated two neoadjuvant anthracycline- and taxane-based regimens with pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer; all patients had normal cardiac function at baseline. Cohort A included 199 patients who received 4 cycles of dose-dense doxorubicin and cyclophosphamide followed by 12 doses of standard paclitaxel plus 4 standard trastuzumab and pertuzumab cycles. In cohort B, 198 patients were treated with 4 cycles of fluorouracil/epirubicin/cyclophosphamide, followed by 4 docetaxel cycles with 4 standard trastuzumab and pertuzumab cycles. Results were published in Annals of Oncology.

Cohorts A and B had median follow-up periods of 14.5 and 15.1 months, respectively. Three patients in cohort A (1.5%) had four New York Heart Association class III/IV heart failure events, with one patient experiencing two events. No patients in cohort B had heart failure events.

In cohort A, 13 patients (6.5%) experienced at least one left ventricular ejection fraction (LVEF) decline; in cohort B, 4 patients (2.0%) had at least one such decline, though one of the four occurred prior to neoadjuvant HER2-targeted therapy. Only two of the cohort A patients and one of the cohort B patients had a confirmed LVEF decline, defined as at least two consecutive readings showing a decline.

Outside of cardiac toxicities, the most common adverse events of any grade included nausea, diarrhea, and alopecia; the most common grade 3/4 events included febrile neutropenia and neutropenia. There were no grade 5 events reported.

The rate of pathologic complete response (pCR) was 61.8% in cohort A and 60.7% in cohort B; rates were higher in patients with hormone receptor–negative disease.

“Treatment with pertuzumab, trastuzumab, and common anthracycline-containing chemotherapy regimens for the neoadjuvant treatment of early breast cancer resulted in cardiac and general safety profiles, and pCR rates, consistent with prior pertuzumab studies,” the authors concluded. “The safety profiles and high pCR rates in both cohorts support the use of pertuzumab and trastuzumab with a taxane following doxorubicin- or epirubicin-based chemotherapy in the neoadjuvant setting.”