Introduction/Background Many gynaecological malignancies including low-grade uterine sarcomas (LGUS), low-grade endometrial carcinomas (LGEC), sex cord stromal tumours (SCST) and low-grade epithelial serous ovarian cancers (LGSC) express oestrogen receptor (ER). Reports suggest that endocrine therapy can be effective, but due to their rarity, no consensus criteria define which patients would benefit from anti-ER treatment.
Methodology FUCHSia is an open-label, single-arm, prospective, multi-centre, tandem two-stage, phase II study evaluating Fulvestrant (Faslodex) efficacy in women with recurrent/metastatic ER-positive gynaecological malignancies. Tumour types studied are LGUS (all LG endometrial stromal sarcoma, adenosarcoma without sarcomatous overgrowth and leiomyosarcoma), LGEC, SCST and LGSC.
Fulvestrant is administered (intramuscular injection, 2 × 250 mg) once every 2 weeks for the first month, and monthly until progression.
In stage 1, 20 patients will be enrolled per tumour type. When 15 patients per type reach week-24, an interim analysis will be performed. If 1 or more responses are observed per type, 30 additional patients will be recruited in stage 2.
Primary endpoint is response rate, determined by RECIST v1.1 criteria.
Secondary endpoints are progression-free survival, overall survival, time to progression, clinical benefit, safety and tolerability, and quality of life.
Exploratory endpoints are feasibility of sequential 18F-FES PET scans for assessment of ER expression and functional status during treatment, value of 18F-FES PET scans combined with 18F-FDG PET scans in predicting response and patient stratification, and identification of genetic changes in cf-DNA and tumour biopsies potentially predicting response to Fulvestrant.
Results UZ Leuven is the sponsor and recruitment is ongoing in UZ Ghent, UZ Antwerp and AZ Sint-Maarten. The study will open soon in NKI/AvL Amsterdam. Additional centres in Belgium and The Netherlands will be added later.
Conclusion In this study, we will assess Fulvestrant activity in low-grade gynaecological cancers, while exploratory endpoints will investigate predictors of response and resistance mechanisms.
Disclosure The authors declare that they have no competing interests. The study obtained funding from ‘Kom op tegen Kanker (Stand up to Cancer), the Flemish cancer society’and ‘FWO - Research Fund Flanders’.
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