ASCO issues guidelines for advanced HER-2–positive breast cancer

ASCO recently issued two clinical practice guidelines on treating women with advanced, HER-2–positive breast cancer, published online in the Journal of Clinical Oncology.

The first guideline reviews the appropriate systemic therapies for patients with newly-diagnosed with advanced disease and those whose early-stage disease progressed to advanced cancer. The second guideline offers recommendations for treating brain metastases in patients with HER-2–positive advanced breast cancer.

The first guideline, Systemic Therapy for Patients with Advanced HER-2–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline, provides evidence-based recommendations for using systemic targeted therapies in treating inoperable locally advanced and metastatic HER-2–positive breast cancer. These recommendations are intended to aid in standardizing care and maximizing the potential benefit from HER-2–targeted therapies.

To develop this guideline, an ASCO Expert Panel conducted a formal systematic review of relevant medical literature. The review identified 19 randomized phase 3 clinical trials on HER-2–targeted therapies, three of which addressed the role of hormonal therapy for HER-2–positive, hormone receptor-positive advanced breast cancer. Based on the review, the panel made recommendations for three lines of therapy, including:

First-line therapy: Combination of chemotherapy, trastuzumab and pertuzumab. For select patients – those with contraindications and/or slow growing hormone receptor-positive cancer – hormonal therapy administered with or without either trastuzumab or lapatinib may be substituted for a chemotherapy-based HER-2–targeted regimen due to fewer side effects. However, hormonal therapy is not appropriate for all patients with advanced, hormone receptor-positive breast cancer since it has not been associated with a survival benefit in this setting.
Second-line therapy: T-DM1
Third-line line therapy: Treatment depends on what patients have received in the first- and second-lines. Options may include T-DM1, hormonal therapy or chemotherapy with tratuzumab and in some cases with lapatinib, the combination of trastuzumab and lapatinib, or pertuzumab-based regimen if the patient had not received pertuzumab beforehand.

“We have several treatments for advanced HER-2–positive breast cancer, all of which are associated with improved survival,” Eric P. Winer, MD, co-chair of ASCO’s Expert Panel that developed the guideline, said in a press release. “We’re very fortunate that now we have multiple studies that give us a clear picture of how these newer agents should be used.”

The second guideline, Recommendations on Disease Management for Patients with Advanced HER-2–Positive Breast Cancer and Brain Metastases: American Society of Clinical Oncology Clinical Practice Guideline, is ASCO’s first formal expert consensus-based clinical practice guideline, and included input from multidisciplinary experts such as neurosurgeons and radiation oncologists.

While brain metastases have been observed in 30-40% of patients living with HER-2–positive breast cancer, there is limited research in this setting and no systemic treatments are specifically approved for brain metastases.

This clinical practice guideline provides consensus-based recommendations for use of local and systemic therapies in patients with HER-2–positive breast cancer that has spread to the brain and is the first guideline explicitly for patients with HER-2–positive metastatic breast cancer.

“Brain metastases can compromise neurologic function, and treatments are designed to preserve neurologic function and minimize the decline in quality of life,” Sharon Giordano, MD, co-chair of the ASCO Expert Panel said in a press release. “But at the same time, some of the treatments for brain metastases have side effects that can negatively affect cognitive function. We hope that this guideline will help standardize care for these patients and balance toxicities and benefits of treatment.”

While it is uncertain whether the treatments for brain metastases prolong survival, many may be effective in managing the symptoms and some may well extend life.

Key recommendations from this guideline include:

For patients with favorable prognosis for survival, surgery and/or radiotherapy are recommended, depending on the size and number of metastases, resectability and symptoms.
For patients with a poor prognosis for survival, options include surgery, whole brain radiation therapy, and systemic therapies with some evidence of activity in the setting of brain metastases, such as lapatinib and capecitabine.

Additional options include best supportive care, enrollment in a clinical trial and/or palliative care.