Levonorgestrel intrauterine device induces response in early endometrial cancer, precancer
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Treatment with a levonorgestrel-dispensing intrauterine device appeared to be effective and safe for women with stage I endometrial adenocarcinoma or endometrial hyperplasia with atypia, according to results of a randomized, phase 2 study.
Results of the study, presented at the virtual Society of Gynecologic Oncology Annual Meeting on Women’s Cancer, showed two-thirds of women had no signs of cancer or precancer in biopsies 6 months after insertion of the intrauterine device (IUD).
Levonorgestrel IUD (LNG-IUD) is available as a contraceptive, and its use as a treatment for endometrial cancer is experimental; however, it could be an option for younger women who wish to preserve fertility or as an alternative to surgery for older, frailer patients, according to the researchers.
“Patients with endometrial hyperplasia with atypia (EHA) have a very high chance of response to LNG-IUD,” Andreas Obermair, MD, professor at The University of Queensland and head of the Queensland Centre for Gynaecological Cancer Research, in Brisbane, Australia, told Healio. “Surgical high-risk cases can be reassured that an alternative is available to them. Patients with endometrial cancer also can be offered [this as] an alternative, but they need to be made aware that the chance of a response is only half.
“If this is adopted by the community I expect [intra- and postoperative] surgical complications to drop significantly,” Obermair added. “Complications are more frequent among obese and super-obese women, and the use of an LNG-IUD is associated with almost no complications.”
Obermair and colleagues sought to determine the extent to which LNG-IUD alone or in combination with either metformin, which typically is used to treat diabetes, or an active weight loss program conferred pathologic complete response among women with endometrial adenocarcinoma (EAC) and EHA.
Researchers enrolled 165 women (mean age, 53 years; mean BMI, 47.7 kg/m2) from December 2012 to October 2019, including 96 women with stage I International Federation of Gynecology and Obstetrics (FIGO) grade 1 EAC and 69 women with EHA. Criteria for participation included BMI greater than 30 kg/m2, myometrial invasion depth of less than 50% on MRI, and a serum CA125 level of at least 30 U/mL.
All women received LNG-IUD (Mirena, Bayer), which consisted of 52 mg levonorgestrel released at a rate of 20 mcg per day.
“Compliance with the intervention was excellent,” Obermair said. “We only lost three patients who expelled the LNG-IUD.”
The primary analysis included women randomly assigned to observation (n = 35), 250 mg twice-daily metformin (n = 47) or weight loss (n = 36), which included a comprehensive subscription to Weight Watchers and encouragement to lose 7% body weight by 6 months.
The proportion of women who achieved pathologic complete response, defined as no evidence of EAC of EHA, at 6 months served as the study’s primary outcome measure.
Most women (n = 154) completed the 6-month follow-up.
After 6 months, results showed pathologic complete response rates of 61% (95% CI, 42-77) for the observation group, 57% (95% CI, 41-72) for the metformin group and 67% (95% CI, 48-82) for the weight loss group.
“We were surprised how well the weight loss group did,” Obermair said. “Patients [randomly assigned] to that arm had a statistically significant better complete pathologic response rate compared with the other two arms. We were not sure initially if patients [randomly assigned] to weight loss would actually be able to lose weight.”
Among all three treatment groups, results showed pathologic complete response rates of 82% for women with EHA and 43% for women with EAC.
During his presentation, Obermair called the pathologic complete response rates “encouraging.”
“This difference in response rates is what previous studies with much smaller case numbers reported, and it is not surprising,” Obermair said. “As cells move from healthy to cancer, they lose capability to respond to levonorgestrel.”
Obermair added that because it was a phase 2 trial, the results did not offer definitive evidence of the effectiveness of the interventions. He recommended further research examining long-term outcomes, such as recurrence, fertility and hysterectomy rates, as well as comparing 6-month and 12-month treatment durations.
“One could argue that the response rate could have been improved slightly by making the treatment duration longer,” he said.
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Obermair A, et al. Abstract 11486. Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (virtual meeting); March 19-25, 2021.
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