HER2-Directed Therapy for Advanced Breast Cancer

Target population: Medical oncologists, radiation oncologists, surgeons, oncology nurses, and patients

Background and Objective

The 15% of breast cancer patients who have tumors that overexpress human epidermal growth factor receptor 2 (HER2) are potential candidates for HER2-directed therapy. During the last decade, several targeted therapies have emerged for treatment of HER2-positive metastatic breast cancer; however, efforts to identify optimal regimens in the first line and beyond — and to evaluate the impact of prior HER2-directed adjuvant therapy — have raised confusion and controversy. An expert panel conducted a systematic literature review of 16 trials from 2009 through 2012 to develop these practice guidelines for treating women with advanced HER2-positive breast cancer.

Key Recommendations

• With rare exceptions, HER2-targeted therapy is recommended in the first line and beyond.

• A combination of trastuzumab, pertuzumab, and a taxane is recommended as first-line therapy unless contraindicated.

• Trastuzumab emtansine (T-DM1) should be offered to patients who experience disease progression during or after first-line HER2-directed therapy.

• If a patient develops disease progression after second-line HER2-directed therapy and has not yet received pertuzumab-based therapy or T-DM1, treatments with these agents can be considered.

• HER2-directed therapy should be continued in patients with disease progression following treatment with pertuzumab or T-DM1. Other options include lapatinib plus capecitabine or trastuzumab, or other combinations of chemotherapy plus trastuzumab.

• If disease recurrence develops within 12 months of completing HER2-directed adjuvant therapy, patients should be offered T-DM1. If disease recurrence occurs >12 months after completion of HER2-directed adjuvant therapy, treatment with trastuzumab, pertuzumab, and a taxane should be offered.

• For patients receiving a combination of chemotherapy plus anti-HER2 therapy, chemotherapy should be continued for 4 to 6 months or until maximal response is achieved, at which time anti-HER2 therapy alone should be continued.

• Select patients with tumors positive for both HER2 and hormone receptors can receive endocrine therapy alone or combined with lapatinib or trastuzumab.