Prospective phase II trial of levonorgestrel intrauterine device: nonsurgical approach for complex atypical hyperplasia and early-stage endometrial cancer
The incidence of complex atypical hyperplasia and early-stage endometrioid endometrial cancer is increasing, in part owing to the epidemic of obesity, which is a risk factor tightly linked to the development of endometrial hyperplasia and cancer. The standard upfront treatment for complex atypical hyperplasia and early-stage endometrial cancer is hysterectomy. However, nonsurgical treatment of early-stage endometrial neoplasia may be necessary owing to medical comorbidities precluding surgery or desired future fertility. This study aimed to evaluate the efficacy of the levonorgestrel intrauterine device to treat complex atypical hyperplasia and grade 1 endometrioid endometrial carcinoma. A single-institution, single-arm, phase II study of the levonorgestrel intrauterine device (52 mg levonorgestrel, Mirena) was conducted in patients with complex atypical hyperplasia or grade 1 endometrioid endometrial cancer. The primary endpoint was pathologic response rate at 12 months, including complete or partial response. Quality of life and toxicity were assessed. Molecular analyses for proliferation markers, hormone-regulated genes, and wingless-related integration site pathway activation were performed at baseline and 3 months. A total of 57 patients were treated (21 endometrial cancer, 36 complex atypical hyperplasia). The median age was 48.0 years, and the median body mass index was 45.5 kg/m The levonorgestrel intrauterine device has a substantial activity in complex atypical hyperplasia and grade 1 endometrioid endometrial cancer, with a modest proportion demonstrating upfront progesterone resistance. Potential biomarkers were identified that may correlate with resistance to therapy; further exploration is warranted.
Authors
Funding
Training of Academic Gynecologic OncologistsCancer Center Support GrantPaul Calabresi Clinical Oncology AwardMD Anderson Gynecologic SPORE for Uterine CancersNCI NIH HHS Grant L30 CA189102MD Anderson Gynecologic SPORE for Uterine CancersClovis Oncology FundingMerck FundingBoehringer Ingelheim FundingGOG Foundation FundingNovartis FundingAmgen FundingEisai FundingAbbVie FundingBristol-Myers Squibb FundingUniversity of Texas MD Anderson Cancer Center Grant 5 T32 CA101642 02University of Texas MD Anderson Cancer Center Grant CA016672Janssen Pharmaceuticals FundingGenentech FundingAstraZeneca Funding