Z-endoxifen emerges as potential breast cancer treatment

Volume 6, Issue 4, 2017


Results of a phase I study in women showed that the treatment was safe and reduced tumors.

Matthew P. Goetz, M.D.

Matthew P. Goetz, M.D.

Z-endoxifen, a potent derivative of the drug tamoxifen, could be a new treatment for the most common form of breast cancer in women with metastatic disease.

This finding was reported from a clinical trial conducted by researchers at Mayo Clinic and the National Cancer Institute. Results of the Z-endoxifen trial were published Aug. 30, 2017, in the Journal of Clinical Oncology.

The final results of a first-in-human phase I study of Z-endoxifen in women with estrogen receptor positive metastatic breast cancer showed that the treatment was safe and resulted in tumor shrinkage in women whose tumors had progressed using standard anti-estrogen therapies, including tamoxifen.

"Tamoxifen is converted into endoxifen in the liver by an enzyme called CYP2D6. Our previous research found that tamoxifen may be less effective in women with poor CYP2D6 metabolism," said Matthew P. Goetz, M.D., the study's lead author and an oncologist at Mayo Clinic in Rochester, Minnesota.

Based on laboratory studies showing that endoxifen better inhibits tumor growth compared with tamoxifen, Dr. Goetz and his colleagues partnered with researchers at the National Cancer Institute to develop Z-endoxifen, an experimental drug unaffected by CYP2D6 metabolism.

"The primary goal of the study was to safely deliver therapeutic levels of endoxifen without the requirement for CYP2D6 liver metabolism," Dr. Goetz said. "However, one of the most surprising observations was the prolonged anti-cancer benefit, which in some cases lasted more than two years in women who had progressed on standard anti-estrogen therapies."

Researchers with the Z-endoxifen clinical trial studied 41 patients with estrogen positive metastatic breast cancer whose cancer had progressed using standard anti-estrogen treatments. The researchers concluded that Z-endoxifen provided substantial drug exposure unaffected by CYP2D6 metabolism, acceptable toxicity and promising anti-tumor activity.

Dr. Goetz and investigators with the Alliance for Clinical Trials in Oncology and the National Cancer Institute recently completed a randomized trial comparing tamoxifen with Z-endoxifen. Results from this Z-endoxifen trial are expected in 2018.

"We are encouraged by these results and are hopeful that based on these data and ongoing studies, Z-endoxifen could become a new Food and Drug Administration-approved treatment for women with estrogen positive metastatic breast cancer," Dr. Goetz said.