Phase 2 study of anastrozole in rare cohorts of patients with estrogen receptor/progesterone receptor positive leiomyosarcomas and carcinosarcomas of the uterine corpus: The PARAGON trial (ANZGOG 0903)

Edmondson, RJ; O&#39;Connell, RL; Banerjee, S; Mileshkin, L; Sykes, P; Beale, P; Fisher, A; Bonaventura, A; Millan, D; Nottley, S; Benson, C; Hamilton, A; Sjoquist, K; Alexander, L; Kelly, C; Carty, K; Divers, L; Bradshaw, N; Friedlander, M; PARAGON investigators

Author(s): Edmondson, RJ; O'Connell, RL; Banerjee, S; Mileshkin, L; Sykes, P; Beale, P; Fisher, A; Bonaventura, A; Millan, D; Nottley, S; Benson, C; Hamilton, A; Sjoquist, K; Alexander, L; Kelly, C; Carty, K; Divers, L; Bradshaw, N; Friedlander, M; PARAGON investigators;
Details: Publication Year 2021-12,Volume 163,Issue #3,Page 524-530
Journal Title: Gynecologic Oncology
Publication Type: Research article
Abstract: BACKGROUND: Aromatase inhibitors have been used empirically to treat a subset of patients with hormone receptor positive uterine leiomyosarcomas(LMS) and carcinosarcomas (UCS) mainly supported by retrospective data. We evaluated the activity of anastrozole in two rare cohorts; patients with recurrent/metastatic LMS and UCS enrolled in PARAGON, a basket trial of anastrozole in estrogen receptor (ER+)/progesterone receptor positive (PR+) gynecological cancers. METHOD: An investigator-initiated, single-arm, prospective open-label trial of anastrozole 1 mg/day in patients with ER &/or PR + ve LMS or UCS with measurable disease, treated until progression or unacceptable toxicity. Primary endpoint was clinical benefit (complete/partial response + stable disease) rate (CBR) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life and toxicity. RESULTS: 39 eligible patients were enrolled, 32 with LMS and 7 with UCS. For the LMS cohort CBR at 3 months was 35% (95% CI: 21-53%) with a median duration of clinical benefit of 5.8 months. Best response was a partial response in one patient. Two patients remained on treatment for more than one year. The median progression-free survival was 2.8 months (95% CI: 2.6-4.9). For the UCS cohort CBR at 3 months was 43% (95% CI: 16-75%) with a median duration of clinical benefit of 5.6 months. Stable disease was seen in 3 patients but no objective responses were seen. The median progression-free survival was 2.7 months (95% CI, 1.1-8.2). Safety was acceptable with 5/39 evaluable patients showing grade 3 toxicities. CONCLUSION: Whilst objective response rates with anastrozole are low, the clinical benefit rate and good tolerance suggests that aromatase inhibitor therapy may have a role in a subset of patients with metastatic LMS and UCS.
Keywords: Adult; Aged; Aged, 80 and over; Anastrozole/adverse effects/*therapeutic use; Aromatase Inhibitors/adverse effects/therapeutic use; Carcinosarcoma/*drug therapy/metabolism/pathology; Female; Humans; Leiomyosarcoma/*drug therapy/metabolism/pathology; Middle Aged; Neoplasm Metastasis; Prospective Studies; Quality of Life; Receptors, Estrogen/metabolism; Receptors, Progesterone/metabolism; Uterine Neoplasms/*drug therapy/metabolism/pathology; Aromatase inhibitor; Uterine carcinosarcoma; Uterine leiomyosarcoma
Department(s): Medical Oncology
PubMed ID: 34625284
Publisher's Version: https://doi.org/10.1016/j.ygyno.2021.09.010
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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