822TiP - BFR ESS: A randomized phase II trial from the GSF/GETO French group evaluating the impact of interruption versus maintenance of aromatase inhibitors in patients with advanced or metastatic low grade endometrial stromal sarcoma after at least 3 years of therapy

Background

Uterine sarcomas are rare tumors with an incidence of 1.7/100 000 women per year, including 20% of endometrial stromal sarcomas (ESS). Patients (pts) with low grade ESS (LGESS) have a good prognosis with 5-year overall survival rates ranging from 66 to 98%, depending on the stage of the disease. Unlike undifferentiated endometrial sarcoma (UES), which behave aggressively, LGESS are indolent. For advanced or metastatic stage, hormonal therapy (HT) is the standard of care. The use of HT for advanced or metastatic disease is recommended based on retrospective data from small series providing evidence that HT have an anti-tumor activity on LGESS. The favorite HT used is aromatase inhibitors (AI). However, if AI are effective and well tolerated, chronical grade 1-2 side-effects have a negative impact on patient’s well-being and need to be balanced in such long-term survival specifically for those with long duration of response (complete or partial). To date, the question of the optimal duration of HT in LGESS is still pending.

Trial design

This open-label randomized multicenter phase II study aims at evaluating the feasibility of interruption of AI in pts with locally advanced or metastatic LGESS after long term stabilization or response to AI. In the interruption arm, AI should be reintroduced as soon as the pt experiences progression (RECIST 1.1). In the maintenance arm, AI must be continued until PD or unacceptable toxicity. The study uses a sequential Bayesian design allowing for continuous monitoring of the main efficacy outcome (6-months progression-free rate), and particularly suited to characterize efficacy signals in the context of a very rare pathology. A maximum sample size of 20 pts per arm will be randomized. OS, time to 1^st subsequent treatment, and outcomes after AI reintroduction (ORR, PFS, and DOR) will be studied; Quality of Life Questionnaire C30 will also provide precious complementary data on patients’ quality of daily living. Fifteen pts are randomized up to date. The first interim analyze is coming soon (after 20 pts randomized).

Clinical trial identification

NCT03624244.

Editorial acknowledgement

Legal entity responsible for the study

Centre Léon Bérard, Lyon, France.

Funding

French Ministry of Health.

Disclosure

All authors have declared no conflicts of interest.