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

BMC Cancer. 2021 Mar 4;21(1):223. doi: 10.1186/s12885-021-07971-w.

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.

Keywords: Brain metastases; Breast cancer; Kadcyla; Stereotactic radiotherapy; Trastuzumab emtansine.

MeSH terms

  • Ado-Trastuzumab Emtansine / adverse effects
  • Ado-Trastuzumab Emtansine / therapeutic use*
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain / pathology
  • Brain Neoplasms / secondary*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Combined Modality Therapy
  • Female
  • Humans
  • Middle Aged
  • Necrosis
  • Radiosurgery* / adverse effects
  • Radiotherapy Dosage
  • Receptor, ErbB-2 / analysis*

Substances

  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Ado-Trastuzumab Emtansine