Trastuzumab Emtansine (T-DM1) and stereotactic radiation in the management of HER2+ breast cancer brain metastases

Abstract

Background Due to recent concerns about the toxicity of trastuzumab emtansine (T-DM1) with stereotactic radiation, we assessed our institutional outcomes treating HER2-positive breast cancer brain metastases (BCBM) with T-DM1 and stereotactic radiation. Methods This is a single institution series of 16 patients with HER2-positive breast cancer who underwent 18 stereotactic sessions to 40 BCBM from 2013 to 2019 with T-DM1 delivered within 6 months. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), distant intracranial control (DIC), and systemic progression-free survival (sPFS) from the date of SRS. A neuro-radiologist independently reviewed follow-up imaging. Results One patient had invasive lobular carcinoma, and 15 patients had invasive ductal carcinoma. All cases were HER2-positive, while 10 were hormone receptor (HR) positive. Twenty-four lesions were treated with stereotactic radiosurgery (SRS) to a median dose of 21 Gy (14–24 Gy). Sixteen lesions were treated with fractionated stereotactic radiation (FSRT) with a median dose of 25 Gy (20-30Gy) delivered in 3 to 5 fractions. Stereotactic radiation was delivered concurrently with T-DM1 in 19 lesions (48%). Median follow up time was 13.2 months from stereotactic radiation. The 1-year LC, DIC, sPFS, and OS were 75, 50, 30, and 67%, respectively. There was 1 case of leptomeningeal progression and 1 case (3%) of symptomatic radionecrosis. Conclusions We demonstrate that stereotactic radiation and T-DM1 is well-tolerated and effective for patients with HER2-positive BCBM. An increased risk for symptomatic radiation necrosis was not noted in our series.

Capecitabine and stereotactic radiation in the management of breast cancer brain metastases

“…Stereotactic radiation technique was conducted as previously described [ 13 , 14 ]. Brain metastases were assessed using magnetic resonance imaging (MRI) (Siemens Sonata, Siemens Medical Systems, Erlangen, Germany) with 1 mm slices for treatment planning purposes prior to the delivery of radiation.…”

“…Patients in this study were followed with examinations by the treating radiation oncologist, neurosurgeon, and/or medical oncologist and with MRI imaging at 2–3-month intervals [ 13 ]. At each visit neurologic status was assessed.…”

Integration of Systemic Therapy and Stereotactic Radiosurgery for Brain Metastases

“…In a separate report, RN was observed in 40% of patients that received T-DM1 [40]. In contrast, Mills et al reported that the combination of SRS and T-DM1 was well tolerated, with only 3% of patients reporting RN [41]. Hence, prospective studies to evaluate the ideal dose of SRS and timing of T-DM1 are warranted.…”

Improving Brain Metastases Outcomes Through Therapeutic Synergy Between Stereotactic Radiosurgery and Targeted Cancer Therapies

“…For this reason, utilization of this drug decreased given that SRS is a mainstay of therapy for patients with brain metastases. However, a recent study by Mills at al reporting on a single institution series of 16 patients with HER-2 positive breast cancer who underwent SRS and T-DM1 therapy delivered within 6 months showed only 1 case (3%) of symptomatic radionecrosis (39). The authors hypothesized that those prior studies showing increased rates of radionecrosis included longer time intervals from radiation and potentially do not accurately reflect toxicity from the combined treatment.…”