Outcomes of Patients With HER2-Positive Breast Cancer Metastatic to Brain Treated With HER2-Targeted Systemic Therapy and Stereotactic Radiosurgery.

PURPOSE/OBJECTIVE(S): For patients with HER2-positive breast cancer metastatic to brain, HER2-directed systemic therapies are increasingly used with stereotactic radiosurgery (SRS), with a goal to avoid or delay whole brain radiotherapy. These include monoclonal antibodies such as trastuzumab (Herceptin, H) and pertuzumab (Perjeta, P), antibody-drug conjugates such as ado-trastuzumab emtansine (T-DM1), and tyrosine kinase inhibitors such as lapatinib. Limited data exist regarding appropriate timing with SRS and outcomes of this treatment regimen for HER2-positive breast cancer metastatic to the brain.

MATERIALS/METHODS: A single-institution retrospective review was performed to identify and collect clinical data on patients with biopsy-proven breast cancer metastatic to the brain who were treated with SRS. Outcomes analyses were performed using the Kaplan-Meier method, and the chi-square statistic was used to compare different treatment groups.

RESULTS: Of 82 patients with breast cancer metastatic to the brain treated with SRS from 2009-2020, 33 (40%) had positive HER2 status, 18 of whom had hormone receptor positivity. At brain metastasis diagnosis, 15 patients (45%) had > 1 intracranial metastasis (range 2-7), and the median maximal brain metastasis dimension was 2.0 cm. Fifteen patients had uncontrolled extracranial disease. After brain metastasis diagnosis, 9 patients (27%) were treated with systemic therapy first (3 with T-DM1, 1 with T-DM1+HP, 1 with lapatinib+HP, 3 with chemotherapy+HP, 1 with chemotherapy) with a median of 18.6 months between the start of systemic therapy and SRS. Seven patients (21%) were treated with SRS first, followed by systemic therapy in 6 of these patients (these were multi-agent regimens with 4 including T-DM1 or lapatinib). Seventeen (52%) received concurrent systemic therapy and SRS upfront (3 with T-DM1, 2 with T-DM1+chemotherapy, 2 with lapatinib, 4 with HP, 5 with hormone therapy, 1 with chemotherapy). Median follow-up time was 21.1 months. Median overall survival was 24.8 months and not statistically different between treatment groups (table). Four patients (12%) developed symptomatic radionecrosis; 3 were on T-DM1 concurrent with SRS (of a total of 10 patients treated with this combination whether upfront or following initial systemic therapy).

CONCLUSION: In this small patient sample, we noted favorable survival outcomes for patients with HER2-positive breast cancer metastatic to the brain when treated with HER2-targeted therapies together with SRS. The sequence of systemic therapy and SRS does not appear to impact survival outcomes. Concurrent treatment with T-DM1 and SRS may be associated with higher rates of radionecrosis.