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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