Intrauterine levonorgestrel (LNG-IUD) demonstrated activity against endometrial adenocarcinoma (EAC) and endometrial hyperplasia with atypia (EHA) according to results of a phase 2 trial (ClinicalTrials.gov Identifier: NCT01686126) published in Gynecologic Oncology.
Although LNG-IUD is already used to treat EAC and EHA, there are limited data that indicate whether it is effective. The aim of this study was to determine if LNG-IUD is effective in this setting and whether the addition of weight loss or metformin can further improve response.
The open-label, 3-arm, phase 2 feMMe trial treated 165 patients with LNG-IUD and then randomly assigned them to observation, a weight-loss intervention, or metformin. Patients had International Federation of Gynecology and Obstetrics (FIGO) grade 1 endometrioid EAC confined to the uterus or EAC with myometrial invasion not more than 50%. The primary endpoint was pathologic complete response (pCR) at 6 months.
The pCR rates were similar across the 3 arms, at 61% in the observation arm, 67% in the weight-loss arm, and 57% in the metformin arm at 6 months. When stratified by disease, the pCR rate was 82% for EHA and 43% for EAC.
The median weight loss in the weight loss group was 8.2 kg, with 19% of the study patients achieving the targeted 7% body weight loss.
The rate of grade 3 adverse events was 3% at 3 months and 4.2% between 3 and 6 months.
The authors concluded that “…complete response rates at 6 months were encouraging for patients with EAC and EHA across the three groups.” The authors added that “[f]uture research is warranted to identify molecular predictors of response to LNG.”
Disclosures: One study author declared affiliations with the pharmaceutical industry. Please see the original article for a full list of authors’ affiliations.
Janda M, Robledo KP, Gebski V, et al. Complete pathological response following levonorgestrel intrauterine device in clinically stage 1 endometrial adenocarcinoma: results of a randomized clinical trial. Gynecol Oncol. 2021;161:143-151. doi:10.1016/j.ygyno.2021.01.029