Development and responses of brain metastases during treatment with trastuzumab emtansine (T-DM1) for HER2 positive advanced breast cancer: A single institution experience.
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ICR Authors
Authors
Okines, A
Irfan, T
Khabra, K
Smith, I
O'Brien, M
Parton, M
Noble, J
Stanway, S
Somaiah, N
Ring, A
Johnston, S
Turner, N
Irfan, T
Khabra, K
Smith, I
O'Brien, M
Parton, M
Noble, J
Stanway, S
Somaiah, N
Ring, A
Johnston, S
Turner, N
Document Type
Journal Article
Date
2018-05-01
Date Accepted
2017-01-23
Abstract
Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that does not cross an intact blood-brain barrier. In the EMILIA trial of T-DM1 vs capecitabine/lapatinib for HER2 positive advanced breast cancer, all patients had baseline brain imaging, and 9/450 (2%) of patients with negative baseline imaging developed new brain disease during T-DM1. We assessed the frequency of brain progression in clinical practice, without routine baseline imaging. We undertook a retrospective study of all patients treated with T-DM1 at the Royal Marsden Hospital from 2011 to 2016. Data collected included baseline characteristics, previous treatment for advanced breast cancer, sites of metastatic disease, duration of T-DM1, sites of progression, and treatment of CNS progression. Fifty-five patients were identified who had received a median of two prior lines of treatment (range 0-5). All were HER2 positive; 45 patients had IHC 3+ tumors and 10 were ISH positive. Patients received a median of 12 cycles of T-DM1 (range 1-34), and six remain on treatment at the time of analysis. Before commencing T-DM1, 16/55 (29%) had known brain metastases (treated with whole brain [9] stereotactic radiotherapy [6] or both [1]). Brain was the first site of progression in 56% (9/16) patients, with a median time to brain progression of 9.9 months (95% CI 3.9-12.2). In patients without known baseline brain metastases, 17.9% (7/39) developed new symptomatic brain disease during T-DM1, after a median of 7.5 months (95%CI 3.8-9.6). Brain progression was isolated, with control of extra-cranial disease in 4/7 patients. Only one patient was suitable for stereotactic radiotherapy. Median time to extra-cranial progression in all patients was 11.5 months (95% CI 9.1-17.7), and median OS in all patients was 17.8 months (95% CI 14.2-22). In patients not screened for brain metastases at baseline, the brain was the first site of progression in a significant proportion. Baseline brain imaging may have a role in standard practice for patients commencing T-DM1 therapy.
Citation
The breast journal, 2018, 24 (3), pp. 253 - 259
Source Title
Publisher
WILEY
ISSN
1075-122X
eISSN
1524-4741
Research Team
Endocrine Therapy Resistance
Molecular Oncology
Medicine (RMH Smith Cunningham)
Treatment of thoracic tumours
Translational Breast Radiobiology
Molecular Oncology
Medicine (RMH Smith Cunningham)
Treatment of thoracic tumours
Translational Breast Radiobiology