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).

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.

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest Dr. Beale reports other from GSK, outside the submitted work. Dr. Sjoquist reports personal fees from Merck, personal fees from Amgen, personal fees from Servier, personal fees from BMS, personal fees from Ipsen, personal fees from Competitive Drug Development, outside the submitted work. Dr. Sykes reports grants from University of Sydney, during the conduct of the study. Dr. Edmondson reports non-financial support from Astra Zeneca, during the conduct of the study; grants from Tesaro (Glaxo Smith Kline), personal fees from Astra Zeneca, personal fees from Clovis Pharmaceuticals, outside the submitted work; Dr. Friedlander reports other from Astra Zeneca, during the conduct of the study, grants personal fees and other from Astra Zeneca, personal fees from MSD, personal fees from GSK, personal fees from Lilly, personal fees from Takeda, grants and personal fees from Novartis, other from Beigene, personal fees from ACT Genomics, outside the submitted work.