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An open-label, single-arm, prospective, multi-center, tandem two-stage designed phase II study to evaluate the efficacy of fulvestrant in women with recurrent/metastatic estrogen receptor-positive gynecological malignancies (FUCHSia study)
  1. Rita Trozzi1,
  2. Sandra Tuyaerts2,
  3. Daniela Annibali3,4,
  4. Alejandro Herreros Pomares3,
  5. Lotte Boog4,
  6. Peter Van Dam5,
  7. Karin Leunen6,
  8. Christophe Deroose7,8,
  9. Hans Trum4 and
  10. Frédéric Amant3,4
    1. 1Department of Women, children and Public health sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
    2. 2Laboratory of Medical and Molecular Oncology (LMMO), Department of Medical Oncology, Vrije Universiteit Brussel, UZ Brussel, Brussel, Belgium
    3. 3Laboratory of Gynecological Oncology, Department of Oncology, KU Leuven, Leuven, Belgium
    4. 4Department of Gynecological Oncology, Antoni van Leeuwenhoek Netherlands Cancer Institute Department of Gynecology, Amsterdam, The Netherlands
    5. 5Division Gynaecological Oncology, Multidisciplinary oncologic Centre, CORE Antwerp University, Edegem, Belgium
    6. 6Gynecology and Obstetrics, AZ Sint-Maarten, Mechelen, Antwerpen, Belgium
    7. 7Nuclear Medicine, University Hospitals Leuven, Leuven, Vlaams-Brabant, Belgium
    8. 8Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Flanders, Belgium
    1. Correspondence to Professor Frédéric Amant, Laboratory of Gynecological Oncology, Department of Oncology, KU Leuven, Leuven 3000, Belgium; frederic.amant{at}uzleuven.be

    Abstract

    Objective This study aimed to evaluate fulvestrant efficacy in women with estrogen receptor-positive low-grade gynecological cancers. The primary objective was to determine the response rate. Secondary objectives were progression-free survival, clinical benefit, duration of response, safety, tolerability, and quality of life.

    Methods FUCHSia is an open-label, single-arm, prospective, multi-center phase II study. The study population included patients with recurrent/metastatic low-grade gynecological malignancies with estrogen receptor positivity who received a maximum of two lines of previous hormonal therapy. Patients received fulvestrant (FASLODEX, AstraZeneca) via two intramuscular injections (250 mg/5 mL each) in the gluteal muscle on day 1, day 15, day 29, and then every 28 days thereafter until disease progression, withdrawal from the trial due to any unacceptable adverse event, or withdrawal of patient consent.

    Results A total of 15 patients (uterine sarcoma n=4; sex cord-stromal ovarian tumors n=3; endometrial carcinoma n=4; serous ovarian cancer n=4) were enrolled. Median follow-up was 48 weeks (interquartile range (IQR) 26–122) in the uterine sarcoma cohort, 63 weeks (IQR 28–77) for sex cord-stromal tumors, 19 weeks (IQR 17–21) for endometrial carcinoma, and 60 weeks (IQR 40–119) for serous ovarian cancer. One partial response according to Response Evaluation Criteria in Solid Tumors v1.1 was observed in one uterine sarcoma patient. No responses were observed in the other cohorts. However, stable disease was observed in three uterine sarcomas (median duration 12 weeks), three sex cord-stromal tumors (median duration 32 weeks), and four low-grade serous ovarian cancer patients (median duration 20 weeks), leading to a disease control rate of 100% for these tumor types. All patients with endometrial carcinoma showed progressive disease.

    Conclusion Fulvestrant may control tumor growth in recurrent/metastatic estrogen receptor-positive low-grade gynecological malignancies of specific histology. Further studies are needed to confirm these results.

    • Genital Neoplasms, Female
    • Ovarian Neoplasms
    • Sex Cord-Gonadal Stromal Tumors
    • Sarcoma

    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

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    Footnotes

    • X @Ritarella_

    • RT and ST contributed equally.

    • Contributors FA,ST,DA contributed to study design, data interpretation; RT, AHP contributed to literature search, and writing of the manuscript; LB,PVD,KL,CD,HT contributed to data collection; ST,AHP contributed to data analysis and generation of figures; FA,DA,ST,LB,PVD,KL,CD,HT contributed in revision of the manuscript. All authors read and approved the final paper. FA act as guarantor.

    • Funding The study was financially supported by Kom Op Tegen Kanker (Stand up to Cancer, the Flemish Cancer Society) and by the Research Foundation Flanders (FWO-TBM program).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.