Preventing brain metastases in patients with HER2 or triple negative breast cancer

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Published: 3 Jun 2019
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Dr Alexandra Zimmer - National Cancer Institute, Bethesda, USA

Dr Alexandra Zimmer speaks to ecancer at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting about ongoing clinical trials looking into the prevention and treatment of brain metastases for patients with HER2 or triple negative breast cancer - the populations who are most likely to develop brain metastases.

She explains that their results indicated that while temozolomide was found to prevent development of brain metastasis in this model, it was not effective as treatment for existing lesions.

Dr Zimmer concludes by describing the next steps of this trial and the patients that will be eligible for participation.

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We have a clinical trial open at the NIH in Bethesda and we have pre-clinical data that was evaluated in our laboratories in the NIH with the Women’s Malignancies branch, the laboratory of Dr Patricia Steeg that studies a lot of the brain metastasis and blood-brain barrier. They evaluated their pre-clinical data looking for different drugs in mice models that we could use to treat or prevent brain metastases for HER2 positive breast cancer or triple negative breast cancer that are the two prevalent populations that develop brain metastases. Interestingly, temozolomide was shown to be a drug that could prevent the development of brain metastases in this mice model but not treat once the lesion is there, established. It will not make a difference as well as in many other drugs that we know and were tested in these models. But temozolomide was effective in preventing the development of even small or big brain metastases in these mice with HER2 positive brain metastases if used earlier. The doses that they used were several doses, even higher going to very low doses and still preventive.

So we saw those results and we searched to develop a clinical trial for the patients. We could not do a preventive trial from the beginning, meaning everybody that has HER2 positive disease will receive, that would be a big, big trial, so we decided to develop a secondary prevention trial. So patients that already have brain metastases from HER2 positive breast cancer and were treated with either CyberKnife, stereotactic radiation, locally treated, surgery, would be eligible for this trial immediately after six weeks or so. The idea is to give temozolomide to these patients from then on to prevent new lesions and associate that with TDM1, which is the Kadcyla that we know, that is a second line drug approved for treatment of HER2 positive metastatic breast cancer. The idea is that the temozolomide doesn’t treat breast cancers so we need that drug to do that, the systemic treatment, so TDM1 is that drug, Kadcyla, and we will be offering temozolomide as well.

We have a good group of patients in the phase I already which is to see the toxicity or safety of the drug. So far it has been safe. I just want to put the word there so that patients know about that possibility. Just get in touch with the NIH and the trial is in the clinicaltrials.gov as well, look for temozolomide and brain metastasis. That could be a good option for these patients.