Temozolomide in secondary prevention of HER2-positive breast cancer brain metastases

Brain metastases occur in up to 25–55% of patients with metastatic HER2-positive breast cancer. Standard treatment has high rates of recurrence or progression, limiting survival and quality of life in most patients. Temozolomide (TMZ) is known to penetrate the blood–brain barrier and is US FDA approved for treatment of glioblastoma. Our group has demonstrated that low doses of TMZ administered in a prophylactic, metronomic fashion can significantly prevent development of brain metastases in murine models of breast cancer. Based on these findings, we initiated a secondary-prevention clinical trial with oral TMZ given to HER2-positive breast cancer patients with brain metastases after recent local treatment in combination with T-DM1 for systemic control of disease. Primary end point is freedom from new brain metastases at 1 year. (NCT03190967).

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Abstract OT2-06-01: Phase I/II study of T-DM1 alone versus T-DM1 and metronomic temozolomide in secondary prevention of HER2-Positive breast cancer brain metastases following stereotactic radiosurgery

10.1158/1538-7445.sabcs17-ot2-06-01 ◽

2018 ◽

Author(s):

AS Zimmer ◽

B Gril ◽

S Steinberg ◽

D Smart ◽

M Gilbert ◽

...

Keyword(s):

Breast Cancer ◽

Secondary Prevention ◽

Brain Metastases ◽

Phase I ◽

Stereotactic Radiosurgery ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Breast Cancer Brain Metastases ◽

Positive Breast Cancer

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Systemic Treatment Options for HER2-Positive Breast Cancer Patients with Brain Metastases beyond Trastuzumab: A Literature Review

Breast Care ◽

10.1159/000467387 ◽

2017 ◽

Vol 12 (3) ◽

pp. 168-171 ◽

Cited By ~ 12

Author(s):

Elena Laakmann ◽

Volkmar Müller ◽

Marcus Schmidt ◽

Isabell Witzel

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Cancer Patients ◽

Systemic Treatment ◽

Treatment Options ◽

Cytotoxic Agents ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

Background: The incidence of brain metastases (BM) in breast cancer patients has increased. Many retrospective analyses have shown that first-line treatment with trastuzumab prolongs survival in patients with HER2-positive BM. In contrast, the evidence for other therapies targeting HER2 for patients with BM is rare. Methods: The aim of this review is to update the reader about current systemic treatment options in patients with HER2-positive metastatic breast cancer with BM who had already received trastuzumab. A literature search was performed in the PubMed database in June 2016. 30 relevant reports concerning the efficacy of trastuzumab emtansine (T-DM1), lapatinib and its combination with other cytotoxic agents, pertuzumab and novel HER2-targeting substances were identified. Results: There is limited but promising evidence for the use of T-DM1 and pertuzumab in the treatment of BM. Up to now, most reported studies used lapatinib as treatment of HER2-positive breast cancer with BM, a treatment with only a modest effect and a high toxicity profile. The combination of lapatinib with cytotoxic agents seems to result in better response rates. Conclusion: Further prospective investigations are needed to investigate the efficacy of the established and novel HER2-targeting agents on BM in HER2-positive breast cancer patients.

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