Pilot Study of Daily Exemestane in Women with Endometrial Intraepithelial Neoplasia or Low Grade Endometrial Cancer

Abstract Objective: To evaluate exemestane, an aromatase inhibitor, as a preventive intervention for endometrial cancer. Methods: This is a multi-center, single-arm, ‘window of opportunity’ pilot study of exemestane (25 mg daily for 21-42 days) in postmenopausal individuals undergoing hysterectomy for endometrial intraepithelial neoplasia (EIN) or low-grade endometrial cancer (EC). The primary objective is to determine change in proliferation, measured by Ki-67 expression, in pre- and post-treatment endometrial tissues specimens. Secondary outcomes include measurement of circulating serum estradiol and progesterone levels, pathologic response, tissue biomarkers, safety, and adverse effects. Results: Forty participants were accrued to the study. Preoperative diagnoses included EIN (n=11, 27.5%), grade 1 EC (n=26, 65%), and grade 2 EC (n=3, 7.5%). Median Ki-67 score decreased from 40.7% IQR (33.9, 50.3) at baseline to 18.1% IQR (8.8, 31.8) at surgery, representing a median absolute change of 20.4% IQR (-29.9, -6.7), p0.001. In a matched historical control cohort, participants also had a decrease in Ki-67 score with a median absolute change from baseline of -6.7% IQR (-12.7, -1.3), p 0.001. However, the decrease in Ki-67 was greater in the study participants than the historic controls, with a median difference between the groups of -13.4% IQR (-23.3, 6.9), p . Both tissue ER and PR expression declined significantly with exemestane treatment (p0.001). However, serum estradiol levels did not change between baseline and post-treatment (p=0.16). Conclusion: In this pilot study, exemestane demonstrated anti-proliferative effects in endometrial intraepithelial neoplasia and low-grade endometrial cancer. This agent warrants further evaluation for the prevention of endometrial cancer.