Temozolomide in secondary prevention of HER2-positive breast cancer brain metastases
Alexandra S Zimmer, Seth M Steinberg, Dee Dee Smart, Mark R Gilbert, Terri S Armstrong, Eric Burton, Nicole Houston, Nadia Biassou, Brunilde Gril, Priscilla K Brastianos, Scott Carter, David Lyden, Stanley Lipkowitz, Patricia S Steeg, Alexandra S Zimmer, Seth M Steinberg, Dee Dee Smart, Mark R Gilbert, Terri S Armstrong, Eric Burton, Nicole Houston, Nadia Biassou, Brunilde Gril, Priscilla K Brastianos, Scott Carter, David Lyden, Stanley Lipkowitz, Patricia S Steeg
Abstract
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).
Keywords: T-DM1; brain metastases; metastatic breast cancer; secondary prevention; temozolomide.
Conflict of interest statement
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Figures
Source: PubMed