Charles L. Shapiro, MD

Charles L. Shapiro, MD, Professor of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, commented on the findings of the coopERA trial for The ASCO Post. He maintained that the oral selective estrogen receptor degraders now in development will be a welcomed addition to the endocrine therapy family—if their benefit is confirmed in phase III randomized trials.

The prototype selective estrogen receptor degrader, fulvestrant, is administered by intramuscular injection into gluteus muscles, “literally a pain in the butt,” he said. Unlike tamoxifen, a selective estrogen receptor modulator and a partial agonist, fulvestrant binds irreversibly to the estrogen receptor and degrades it. It has been shown to be superior to anastrozole in the front-line treatment of advanced estrogen receptor–positive, HER2-negative breast cancer.

“The oral selective estrogen receptor degraders are a promising alternative to fulvestrant, and some preclinical studies even show superiority of the oral selective estrogen receptor degraders over fulvestrant,” Dr. Shapiro said.

The results of the neoadjuvant coopERA trial in 109 women (83 of whom had baseline and 2-week Ki67 measurements) showed that Ki67—a biomarker of proliferation and the primary endpoint of this trial—was reduced more in patients on oral giredestrant than on anastrozole in the 2-week “window-of-opportunity” trial. However, he added, these results did not reach statistical significance in the prespecified analysis.

What Now?

So, what do the results of the coopERA trial interim analysis mean? “They are somewhat promising but very preliminary,” Dr. Shapiro commented. “With small numbers of women, the lack of statistical significance and the clinical importance of these results will not be clear until we see data from phase III randomized trials of the oral selective estrogen receptor degraders alone or in combination with CDK4/6 inhibitors, which are currently in progress. Stay tuned!” 

DISCLOSURE: Dr. Shapiro reported no conflicts of interest.