New Clinical Trial Results on Temozolomide & Brain Metastases

New clinical trial shows promising results for preventing breast cancer reappearing in the brain.

Breast cancer spreading to the brain (brain metastases, or brain mets) can occur in up to 25-55% of HER2-positive secondary breast cancer patients. Brain metastases in secondary breast cancer patients is treated with radiotherapy and/or surgery. However, after these treatments brain metastases can still reappear. A phase I clinical trial has recently investigated if a new drug combination can prevent metastatic breast tumours from recurring in the brains of women who have had previous treatment for brain mets. 

Twelve trial participants had secondary HER2-positive breast cancer and radiotherapy and/or surgery for brain metastases in the past 12-weeks. They received a new drug combination of T-DM1 (also known as Trastuzumab emtansine or Kadcyla®) and low-dose temozolomide (TMZ). TDM1 is regularly given to patients who have secondary HER2-positive breast cancer and is part of the standard practice of care. However, TMZ is a chemotherapy that is approved for certain types of brain tumours (e.g., a malignant glioma) but is being researched for other cancers that have spread to the brain. 

Importantly, TMZ has the ability to cross the blood-brain barrier, which typically prevents most drugs from entering the brain. TMZ does not appear to shrink metastatic breast cancer tumours once they have established themselves in the brain, however, mice studies have shown that a low daily dose of the drug can prevent these tumours from forming. This phase 1 clinical trial wanted to investigate if TMZ could prevent brain tumours from forming in HER2-positive secondary breast cancer patients, to build on these mice findings. 

None of the twelve patients recruited into this new clinical trial of TDM1 & TMZ had detectable brain tumours at the start of the trial. However, half of the patients did have cancer-associated DNA present in their brains when their cerebrospinal fluid was analysed. This suggests that cancer cells were present in the brain, putting the patients at very high risk of recurrence of brain mets. 

In the trial patients received standard doses of TDM1 and TMZ daily at one of three doses. All experimental TMZ doses were low compared to the dose of TMZ that is used in a treatment setting. Participants were followed for an average of 9.6 months. The drug combination was well tolerated, with limited side effects and only two out of the twelve patients developed new brain tumours. 

Although this is a small study, with a low number of participants, this is a promising result that potentially shows that the new combination of TDM1 and TMZ could prevent brain metastasis recurrence in secondary HER2-positive breast cancer patients. 

TMZ is also being researched as a prevention for secondary breast cancer metastasis in women with triple-negative breast cancer, but the clinical trial (NCT05128734) has yet to start recruiting.  

If you are interested in learning more about clinical trials you can enrol into the Patients Trial Advocate (PTA) service and speak to research nurses to learn more about them. You can also view the Make 2nds Count clinical trial registry of all of the actively recruiting secondary breast cancer trials in the UK.