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

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

Matthew N Mills  1 , Chelsea Walker  2 , Chetna Thawani  2 , Afrin Naz  2 , Nicholas B Figura  3 , Sergiy Kushchayev  4 , Arnold Etame  5 , Hsiang-Hsuan Michael Yu  3 , Timothy J Robinson  3 , James Liu  5 , Michael A Vogelbaum  5 , Peter A Forsyth  5 , Brian J Czerniecki  6 , Hatem H Soliman  6 , Hyo S Han  6 , Kamran A Ahmed  3
Affiliations

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

Matthew N Mills et al. BMC Cancer. .

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.

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Conflict of interest statement

Hyo S. Han declares that she has received a speaker’s honorarium from Lilly Pharmaceuticals, research funding from Abbvie, Tesaro, TapImmune, Novartis, Bristol-Myers Squibb, Pfizer, SeattleGenetics, Prescient, Horizon, and Karyopharm. Peter A. Forsyth has received research funding from Pfizer and Celgene and is on the advisory boards of Novocure, BTG, Inovio, AbbVie, Ziopharm, Tocagen, and Pfizer. Kamran A. Ahmed has received research funding from Bristol-Myers Squibb and Genentech. Michael A. Vogelbaum has indirect equity and royalty interests in Infuseon Therapeutics, Inc. and has received honoraria from Tocagen, Inc. and Celgene. Hatem Soliman serves as a consultant for Astrazeneca, Celgene, Novartis, PUMA, and Eisai. Brian J Czerniecki has intellectual property on a HER2 dendritic cell vaccine. Hsiang-Hsuan Michael Yu has received speaker’s honoraria from BrainLab and is on the advisory boards of Novocure and Abbvie.

Figures

Fig. 1
Fig. 1
Kaplan-Meier a) local control and b) distant control following stereotactic radiation
Fig. 2
Fig. 2
Kaplan-Meier overall survival following stereotactic radiation
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