New ASCO Guidelines for Treating HER2-Positive Breast Cancer

Two new clinical guidelines on treating patients with HER2-positive breast cancer have been issued by the American Society of Clinical Oncology (ASCO), with the goal of helping to standardize and optimize care for patients.

The first is a guide to systemic treatment for advanced HER2-positive disease. The guideline was published in the Journal of Clinical Oncology on May 5. With four US Food and Drug Administration (FDA)-approved therapies associated with improved survival for HER2-positive metastatic disease, the guideline provides an evidence-based road map of how to best utilize these newer agents. Lapatinib, trastuzumab, pertuzumab, and trastuzumab emtansine (T-DM1) can all increase survival for patients and generally have been shown to have fewer side effects compared with chemotherapy.

The authors of this guideline included 16 randomized phase III clinical trials on HER2-targeted therapy that were published in peer-reviewed journals. Three of these studies addressed the efficacy of hormonal therapy for those patients with HER2-positive and hormone receptor (HR)–positive advanced breast cancer.

The main recommendations are for three lines of therapy:

• First-line therapy: combination of trastuzumab, pertuzumab, and chemotherapy. For certain patients, such as those with contraindications or slow-growing estrogen receptor (ER)-positive cancer, hormonal therapy given with or without trastuzumab or lapatinib may be substituted for a chemotherapy-based, HER2-targeted regimen, according to the guideline, as this regimen may result in fewer side effects. Hormonal therapy, however, is not appropriate for all metastatic HER2- and HR-positive patients, and has not been linked with a survival benefit.

• Second-line therapy: T-DM1.

• Third-line and further lines of therapy: This line of therapy depends on what patients received in previous lines of therapy. Options include T-DM1, hormonal therapy, or chemotherapy with trastuzumab. Lapatinib, the combination of trastuzumab and lapatinib, or a pertuzumab-based regimen-if the patient has not previously received pertuzumab-may also be appropriate.

Consensus-Based Guide for Treating Brain Metastases in HER2-Positive Breast Cancer Patients

The second guideline, also published in the Journal of Clinical Oncology, is the first consensus-based recommendation of local and systemic therapies for treating HER2-positive breast cancer patients who have brain metastases. No systemic treatments are currently approved for brain metastases in this patient population. According to the guidelines, although survival of patients diagnosed with brain metastases has historically been quite poor,  “in the case of HER2-positive breast cancer, as systemic therapies for control of extracranial disease improve, an increasing number of patients are experiencing extended survival.” Even with multiple brain metastases, women with HER2-positive disease can live for 2 or more years, according to the authors.

The main recommendations are for three lines of therapy:

• Surgery with or without radiotherapy is recommended for patients with a favorable prognosis for survival, depending on the size and number of brain metastases, symptoms, and resectability.

• For those patients who have a poor prognosis, surgery, whole-brain radiation therapy, and systemic therapies (lapatinib and capecitabine, for example) with evidence of activity specifically on brain metastases are all potential options.

• Other options include best supportive care, enrollment in a clinical trial, and palliative care.

ASCO also issued a summary of these guidelines for patients and caregivers.