Pilot Study of Daily Exemestane in Women with Endometrial Intraepithelial Neoplasia or Low Grade Endometrial Cancer
Menée sur 40 patientes atteintes d'une néoplasie intraépithéliale de l'endomètre ou d'un cancer de l'endomètre de bas grade et subissant une hystérectomie, cette étude multicentrique évalue l'efficacité, du point de vue l'évolution de la prolifération tumorale mesurée par l'expression de Ki-67, de l'exémestane dispensé quotidiennement
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), p<0.001]. 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 (p<0.001). 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.
Clinical Cancer Research , résumé, 2025