Patients with HER2-positive tumors should, with rare exception, continue to receive systemic HER2-directed therapy even after disease progression.

Sponsoring Organization: American Society of Clinical Oncology

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.

COMMENT

These guidelines clearly emphasize that patients with HER2-positive tumors should, with rare exception, continue to receive systemic HER2-directed therapy even after disease progression. In select patients with comorbidities or therapy-related toxicity (i.e., cardiac dysfunction), such conditions should be taken into account when considering HER2-directed therapy. Additional HER2-directed agents (e.g., neratinib) are in development and could provide more options.

William J. Gradishar, MD reviewing Giordano SH et al. J Clin Oncol 2014 May 5.

CITATION(S):

Giordano SH et al. Systemic therapy for patients with advanced human epidermal growth factor receptor 2–positive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2014 May 5; [e-pub ahead of print].
[Free full-text J Clin Oncol article PDF | PubMed® abstract]

 

 

 

 

 

 

 

 

 

 

 

 

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