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, R. J. et al. (2021) 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). Gynecologic Oncology, 163(3), pp. 524-530. (doi: 10.1016/j.ygyno.2021.09.010) (PMID:34625284)

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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.

Item Type:Articles
Additional Information:This research was supported by a Cancer Australia Grant 632740 (2009–2011), Cancer Australia Priority-Driven Collaborative Research Scheme Project Grant 1063014 (2014–2016), Cancer Australia Priority-Driven Collaborative Cancer Research Scheme Project Grant 1142697, Cancer Research UK (C22375/A12846 and C22375/A13784), and Cancer Institute New South Wales Research Infrastructure Grant 15/RIG/1-16. UK Co-Sponsors: NHS Greater Glasgow and Clyde and University of Glasgow. Anastrozole was provided by AstraZeneca.
Keywords:Aromatase inhibitor, Uterine leiomyosarcoma, Uterine carcinosarcoma
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Alexander, Mrs Laura and Millan, Dr David and Kelly, Mrs Caroline and Carty, Mrs Karen and Divers, Miss Laura
Authors: Edmondson, R. J., O'Connell, R. L., 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., and on behalf of PARAGON investigators,
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Gynecologic Oncology
Publisher:Elsevier
ISSN:0090-8258
ISSN (Online):1095-6859
Published Online:05 October 2021

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
164893PARAGON - Phase II study of aromatase inhibitors in women with potentially hormone response recurrent/metastatic gynaecological neoplasmsJames PaulCancer Research UK (CRUK)C22375/A12846CS - Clinical Trials UInit Gartnavel
166881TRANS PARAGON - Translational research in potentially hormone responsive recurrent/metastic gynaecological neoplasms.James PaulCancer Research UK (CRUK)C22375/A13784CS - Clinical Trials UInit Gartnavel