Alternative Chemo Formulations May Help Reduce Cardiac Toxicity in HER2+ Breast Cancer

Combining dual HER2 blockade using trastuzumab and pertuzumab with paclitaxel and non-pegylated liposomal doxorubicin may help lower the incidence of cardiac toxicity in patients with early HER2-positive breast cancer, according to a new study.

Based on earlier research, dual HER2 blockade in combination with chemotherapy has become the standard of care in first-line advanced disease, and will likely become more widely used in early breast cancer as well. “In this context, cardiac dysfunction induced by anti–HER2-based chemotherapy needs attention,” wrote study authors led by Joaquín Gavilá, MD, of the Fundación Instituto Valenciano de Oncología in Valencia, Spain. Relatively high rates of cardiac toxicity have been observed in the past; liposomal formulations of chemotherapy agents may offer some reduction, and the Opti-HER HEART trial examined this question.

The study included 83 patients with stage II–IIIB HER2-positive breast cancer; all were treated with neoadjuvant trastuzumab, pertuzumab, paclitaxel, and non-pegylated liposomal doxorubicin every 3 weeks for 6 cycles. The mean age in the trial was 49.5 years, and most patients were premenopausal (65.1%) and had hormone receptor (HR)-positive disease (68.7%). Results of the study were published in BMC Medicine.

The incidence of cardiac events during neoadjuvant therapy was 2.4%; these events occurred in two patients, and both were decreases in left ventricular ejection fraction (LVEF; absolute decrease of 45% and 38%). There were no cases of heart failure.

During adjuvant treatment with trastuzumab following surgery, four additional patients (5.1%) presented with a cardiac event, again all represented by LVEF increases.

The most frequent grade 3 or 4 adverse events during neoadjuvant therapy included neutropenia (34%), asthenia/fatigue (13.3%), mucositis (9.6%), and diarrhea (7.2%).

A total of 47 patients (56.6%) achieved a pathologic complete response (pCR) in the breast and the axilla, and those with HR-negative disease had a higher pCR rate than those with HR-positive disease (76.9% vs 47.3%). The overall response rate in the study was 91.3%, and only one patient had disease progression while on study treatment. An analysis of gene expression found that patients with a HER2-enriched subtype had a very high pCR rate, of approximately 80%.

“The combination of trastuzumab, pertuzumab, paclitaxel, and non-pegylated liposomal doxorubicin is associated with a low rate of cardiac events,” the authors concluded.

William J. Gradishar, MD, of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago, who was not involved with the research, told Cancer Network that minimizing cardiac toxicity while optimizing efficacy has been a particular focus of recent research in HER2-positive breast cancer. “One potential way to continue the use of an anthracycline with HER2-directed therapy is to use other preparations such as liposomal formulations,” he said. “This study suggests that such a strategy is both effective and safe from a cardiac standpoint.”