Phase 2 study of anastrozole in patients with estrogen receptor/progesterone receptor positive recurrent low-grade endometrial stromal sarcomas: The PARAGON trial (ANZGOG 0903)

Friedlander, M. et al. (2021) Phase 2 study of anastrozole in patients with estrogen receptor/progesterone receptor positive recurrent low-grade endometrial stromal sarcomas: The PARAGON trial (ANZGOG 0903). Gynecologic Oncology, 161(1), pp. 160-165. (doi: 10.1016/j.ygyno.2021.02.016) (PMID:33608144)

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Background: Aromatase inhibitors are standard of care for low-grade endometrial stromal sarcomas (LGESS), based on very high response rates reported in retrospective studies. We evaluated the activity of anastrozole in recurrent/metastatic LGESS patients enrolled in PARAGON, a basket trial of anastrozole in estrogen receptor (ER±)/progesterone receptor (PR+) gynecological cancers. Method: An investigator-initiated, single-arm, prospective open-label trial of anastrozole 1 mg/day in patients with ER ± PR + ve LGESS with measurable disease, treated until progressive disease 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: 15 eligible patients were enrolled. CBR at 3 months was 73% (95% CI: 48–89.1%); unchanged at 6 months. Best response was 26.7%, including complete response in one (6.7%; 95% CI 1.2–29.8%), partial response in three (20%, 95% CI 7.1–45.2%) and stable disease in seven (46.7%). Four patients ceased treatment by 3 months due to progression. Median PFS was not reached (25th percentile: 2.9 months (95% CI: 1.2–NR)). PFS was 73.3%, 73.3% and 66% at 6, 12, and 18 months, respectively. Six patients remained on treatment for an average of 44.2 months (range 34.5–63.6) up until data cut. Toxicity was as expected, with 3 patients stopping due to adverse effects. Conclusion: The 26.7% objective response rate with anastrozole is lower than reported in retrospective series, but the CBR was high and durable. The results underscore the importance of prospective trials in rare cancers.

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. FA is a senior researcher for the Flemish Research Fund Flanders (FWO). LM was supported by a Clinical Research Fellowship from the Victorian Cancer Agency. Anastrozole was provided by AstraZeneca. We thank Dr. Sherilyn Goldstone for editorial assistance.
Keywords:Anastrazole, Aromatase inhibitors, Endometrial stromal, Uterine sarcoma, sarcomas
Glasgow Author(s) Enlighten ID:Millan, Dr David and Kelly, Mrs Caroline and Alexander, Mrs Laura and Divers, Miss Laura
Authors: Friedlander, M., Benson, C., O'Connell, R. L., Reed, N., Clamp, A., Lord, R., Millan, D., Nottley, S., Amant, F., Steer, C., Anand, A., Mileshkin, L., Beale, P., Banerjee, S., Bradshaw, N., Kelly, C., Carty, K., Divers, L., Alexander, L., and Edmondson, R.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Gynecologic Oncology
ISSN (Online):1095-6859
Published Online:16 February 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