Basket study of oral progesterone antagonist onapristone extended release in progesterone receptor-positive recurrent granulosa cell, low-grade serous ovarian cancer, or endometrioid endometrial cancer Journal Article


Authors: Andres, S.; Finch, L.; Iasonos, A.; Zhou, Q.; Girshman, J.; Chhetri-Long, R.; Green, H.; Jang, D.; O'Cearbhaill, R.; Kyi, C.; Cohen, S.; Friedman, C.; Makker, V.; Chi, D. S.; Sonoda, Y.; Chiang, S.; Aghajanian, C.; Weigelt, B.; Grisham, R. N.
Article Title: Basket study of oral progesterone antagonist onapristone extended release in progesterone receptor-positive recurrent granulosa cell, low-grade serous ovarian cancer, or endometrioid endometrial cancer
Abstract: Objective: To determine the safety and efficacy of the oral progesterone antagonist onapristone extended release (onapristone-XR) in patients with recurrent progesterone receptor (PR)-positive adult-type granulosa cell tumor (aGCT), low-grade serous ovarian cancer (LGSOC), or endometrioid endometrial cancer (EEC). Methods: This single-institution phase II study included patients with PR-positive aGCT, LGSOC, or EEC who received ≥1 prior line of chemotherapy. Patients were enrolled from 5/2019–5/2020. PR status was evaluated via immunohistochemistry. Eligible patients had PR expression ≥1% on tissue collected within 3 years of enrollment. Patients received 50 mg of onapristone-XR twice daily until disease progression or treatment discontinuation. Adverse events were graded by Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints were response duration, clinical benefit rate (CBR), and safety. Results: Five patients with LGSOC and 1 with EEC enrolled, but both cohorts closed early due to slow accrual. Fourteen patients with aGCT enrolled and completed stage 1 accrual. No responses were observed. Four patients with LGSOC were evaluable, with median PFS of 4.4 months (range, 1.8-NE) and CBR of 50% (range, 6.8%–93.2%). All 14 patients with aGCT were evaluable, with median PFS of 2.8 months (range, 1.6–4.9), 6-month PFS rate of 21.4% (range, 5.2%–44.8%), 12-month PFS rate of 14.3% (range, 2.3%–36.6%), and a CBR of 35.7% (range, 12.8%–64.9%). Conclusions: The study did not meet its primary endpoint. While onapristone-XR was well tolerated in all 3 arms, no objective responses were observed. © 2024
Keywords: immunohistochemistry; adult; controlled study; human tissue; aged; major clinical study; treatment duration; endometrium cancer; ovarian cancer; ovary cancer; phase 2 clinical trial; anemia; drug effect; abdominal pain; febrile neutropenia; lymphocytopenia; immunotherapy; thromboembolism; urinary tract infection; granulosa cell tumor; hormonal therapy; small intestine obstruction; overall response rate; granulosa cell; response evaluation criteria in solid tumors; serous ovarian cancer; human; female; article; protein expression level; endometrioid endometrial cancer; onapristone; progesterone receptor expression
Journal Title: Gynecologic Oncology
Volume: 189
ISSN: 0090-8258
Publisher: Elsevier Inc.  
Date Published: 2024-10-01
Start Page: 30
End Page: 36
Language: English
DOI: 10.1016/j.ygyno.2024.06.026
PROVIDER: scopus
PUBMED: 38991472
PMCID: PMC11867184
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Rachel N. Grisham -- Source: Scopus
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MSK Authors
  1. Vicky Makker
    265 Makker
  2. Dennis S Chi
    707 Chi
  3. Yukio Sonoda
    473 Sonoda
  4. Qin Zhou
    254 Zhou
  5. Alexia Elia Iasonos
    363 Iasonos
  6. Rachel Nicole Grisham
    170 Grisham
  7. Sara Cohen
    11 Cohen
  8. Britta Weigelt
    633 Weigelt
  9. Claire Frances Friedman
    118 Friedman
  10. Chrisann Kyi Kyi
    39 Kyi
  11. Seth Matthew Cohen
    21 Cohen
  12. Dasom Jang
    5 Jang
  13. Lindsey Adams Finch
    11 Finch
  14. Hunter Green
    18 Green
  15. Sarah Andres
    6 Andres