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

Abstract

To evaluate exemestane, an aromatase inhibitor, as a preventive intervention for endometrial cancer. This is a multicenter, 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. The primary objective is to determine the change in proliferation, measured by Ki-67 expression, in pre- and posttreatment endometrial tissue specimens. Secondary outcomes include measurement of circulating serum estradiol and progesterone levels, pathologic response, tissue biomarkers, safety, and adverse effects. Forty participants were accrued to the study. The mean body mass index was 40.3 (range, 22.8-60.5, SD = 9.8). Preoperative diagnoses included EIN (n = 11, 27.5%), grade 1 endometrial cancer (n = 26, 65%), and grade 2 endometrial cancer (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 from baseline of 20.4% [IQR (-29.9, -6.7), P < 0.001]. In a matched historic 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 ≤ 0.01]. Both tissue estrogen receptor and progesterone receptor expression declined significantly with exemestane treatment (P < 0.001). However, serum estradiol levels did not change between baseline and after treatment (P = 0.16). In this pilot study, exemestane demonstrated antiproliferative effects in EIN and low-grade endometrial cancer. This agent warrants further evaluation for the prevention of endometrial cancer.