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Hormonal therapy with a levonorgestrel-releasing intrauterine device (LNG-IUD) led to a high pathological complete response (pCR) rate in women with early-stage endometrial cancer, according to the feMMe trial presented at SGO 2021 Meeting.
In the open-label phase II trial, 165 patients (mean age 53 years) were randomized in a 3:3:5 ratio to treatment with the IUD (52 mg levonorgestrel) plus either observation only, a weight-loss intervention, or metformin 250 mg twice daily. Patients were women diagnosed with either endometrial adenocarcinoma (EAC; 58 percent) or endometrial hyperplasia with atypia (EHA; 42 percent). [SGO 2021, abstract 11486]
Presenting author Dr Andreas Obermair from the University of Queensland in Brisbane, Australia, explained that metformin is a commonly used anti-diabetic drug which has been shown to confer anti-proliferative effects on endometrial cancer cells in vitro. On the other hand, weight loss was previously shown to reduce the risk of EAC and improve overall survival in EAC patients.
At 6 months, 61 percent (95 percent confidence interval [CI], 42-77) of women in the IUD plus observation group achieved pCR. This rate was 67 percent (95 percent CI, 48-82) in those who also participated in the weight loss programme and 57 percent (95 percent CI, 41-72) in those who took metformin, both in addition to IUD.
“A pCR rate of at least a 60 percent with either combination would provide sufficient evidence for informing any subsequent phase III trial, [with the] lower CI bound excluding 45 percent, upper bound includes 75 percent,” informed Obermair.
“Complete response rates at 6 months were encouraging for patients with EAC and EHA across the three groups,” he noted. “[It appears that] weight loss may accelerate response to progestin treatment.”
When stratified by disease diagnosis, the clinical benefit was particularly pronounced in women with EHA, which significantly predicted pCR, compared with women with EAC (82 percent vs 43 percent; p<0.001).
In addition, the treatment was safe with minimal side effects and overall compliance has been high, with three out of the 165 women had their IUD removed, Obermair reported.
“[The] standard treatment of endometrial cancer is total hysterectomy, bilateral salpingo-oophorectomy with or without surgical staging,” he stated. “However, for two groups of patients this is challenging — for young women who wish to preserve fertility and also for elderly and frail women with multiple medical comorbidities who are at risk of prolonged hospital stay, higher risk for procedure-related adverse events, and high cost.”
“Professional societies, clinicians, and patient groups have called for effective, non-surgical treatments,” Obermair explained. “LNG-IUD has been offered ad-hoc to patients who are not suitable for surgery … but robust evidence is lacking”
While results from this phase II study on LNG-IUD have been encouraging, these do not constitute definitive evidence on effectiveness of the intervention and further studies are warranted, he said.
Obermair suggested that future research be done to investigate different treatment duration of 6 vs 12 months treatment, to find out predictive factors that would identify patients who are likely to respond, and to understand the long-term outcomes with regard to recurrence, fertility, and hysterectomy rates.
Muhammad Sobri Maulana