Dr Lin on the Selection of Systemic Therapy in HER2+ Breast Cancer With Brain Metastases

Nancy U. Lin, MD, associate chief, Division of Breast Oncology, Dana-Farber Cancer Institute, Susan F. Smith Center for Women’s Cancers, director, Metastatic Breast Cancer Program, Program for Patients with Breast Cancer Brain Metastases, senior physician, associate professor of medicine, Harvard Medical School, discusses selecting between systemic vs local therapy for patients with HER2-positive breast cancer displaying central nervous system (CNS) metastases.

For years, radiation therapy has been the established standard of care for the majority of patients with brain metastases, Lin begins. However, the selection of treatment approaches involving systemic therapies and radiation therapy continues to evolve as the role of systemic therapy is further elucidated, Lin states.

The decision to defer radiation therapy in favor of initial systemic therapy in patients with breast cancer brain metastases is complex, and requires consideration of several patient and disease characteristics. Surgical resection is commonly offered to patients who have very symptomatic or large lesions, Lin states. It is also considered in situations where there is a diagnostic dilemma, she adds.

There are now several effective systemic options for patients with HER2-positive breast cancer brain metastases, Lin continues. These agents have displayed decent CNS response rates and reasonable progression-free survival rates.

The HER2CLIMB regimen of tucatinib (Tukysa) plus trastuzumab (Herceptin) and capecitabine (Xeloda) is one particularly attractive treatment option, Lin details. The phase 2 HER2CLIMB (NCT02614794) trial was one of the first to demonstrate the potential for this systemic therapy to substantially improve survival outcomes vs whole brain radiation therapy for patients with both treated and stable, as well as active brain metastases, Lin says.

Howerver, as patients live longer, there are concerns about late toxicities associated with radiation therapy, Lin notes. Therefore, the efficacy of these agents raises the question of whether radiation-sparing approaches can be utilized more in clinical practice, she states.

In general, whole brain radiation therapy should be deferred as long as is reasonable for patients with HER2-positive disease, Lin advises. Those who have never received a prior tucatinib-based regimen or fam-trastuzumab deruxtecan-nxki (Enhertu) should be offered those regimens prior to radiation, as the resulting response rates may be high enough to further prolong time without radiation, she concludes.