Tamoxifen Metabolite Z-Endoxifen in Metastatic Breast Cancer
By: Susan Reckling
Posted: Tuesday, September 26, 2017
The oral tamoxifen metabolite Z-endoxifen showed substantial drug exposure, acceptable toxicity, and antitumor activity in patients with endocrine-refractory metastatic breast cancer. The results of this first-in-human phase I study were reported by Matthew P. Goetz, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues in the Journal of Clinical Oncology.
A total of 38 evaluable patients received oral Z-endoxifen at 7 dose levels, ranging from 20 to 160 mg/day. Disease progression had occurred in these patients, who had received prior endocrine regimens, such as an aromatase inhibitor, fulvestrant, and tamoxifen.
Overall, three patients had a partial response, and stable disease of more than 6 months was reported in seven patients, for a clinical benefit rate of 26.3%. “One of the most surprising observations was the prolonged anticancer benefit, [which] in some cases lasted more than 2 years in women who had progressed on standard antiestrogen therapies," stated Dr. Goetz in a Mayo Clinic press release.
Shorter progression-free survival was seen in 13 patients who had circulating cell free DNA mutations, which included PIK3CA, TP53, and AKT. In addition, clinical benefit was reported in those with ESR1 amplification and ESR1 mutation.