19O - AIMET: A EURACAN multicenter pilot study of aromatase inhibitors plus metformin on recurrent granulosa cell tumors

Background

The purpose of the pilot study was to evaluate the effect of aromatase inhibitors (AI) in combination with metformin (MET) in relapse setting in pre-treated patients with recurrent ovarian granulosa cell tumors.

Methods

The twenty-one women with relapsed granulosa cell tumors, previously treated with AI were identified and included in a AIMET study in period May 2020-February 2024, 12 of them were advised AIMET after discussion on EURACAN MDT. The other patients were included by the EURACAN centers themselves. Of these 21 women, 8 pts were from Norway, 5 pts from England, 4 pts from France, 2 pts from Sweden, 1 woman from Italy and 1patient from Spain. All included patients were advised combination Letrozole 2.5 mg/d plus Metformin 500mg/d, some of the patients received Metformin 1000mg/d. The primary endpoint was to assess response rate, clinical benefit and safety.

Results

The median age at inclusion was 58 years (26-71). Two patients had juvenile granulosa cell tumor; all other women had adult granulosa cell tumors. Fifteen patients had FIGO stage I at primary diagnosis, while the other five women had stage >II. All patients underwent surgical treatment at primary diagnosis, followed by chemotherapy in seven of them. All patients experienced multiple relapses and underwent surgical treatment, several lines chemotherapies and hormonal treatment with AI. The best response to AIMET combination we have observed was Partial Response 4 pts (19%). The median duration of AIMET treatment in this group was 28 months (12-45). Eleven women (53%) had stable disease or slowly progression. The median duration of AIMET treatment in this group was 16 months (2-63), and 6 women (28%) had progressive disease with median duration of treatment 10 months (3-30). Most of the women used combination Letrozol+metformin 500/1000mg, 40 % of patient reported mild gastrointestinal symptoms as side effects. Only one patient had to interrupt her treatment due to AES grade 3. One patient died due to disease progression; the other 20 patients are still alive.

Conclusions

Our results show promising effect and excellent tolerability of endocrine therapy with addition of metformin in pre-treated patients with recurrent ovarian granulosa cell tumors.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.