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

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.

Informations de copyright

Copyright © 2021. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of Competing Interest MF reports personal fees from Astra Zeneca, MSD, GSK, Tesaro, Lilly and Novartis; institutional grants from Astra Zeneca, Novartis and Beigene, and travel support from Astra Zeneca outside the submitted work. AC reports grants from Astra Zeneca outside the submitted work. RL reports travel and education support from Astra Zeneca outside the submitted work. CS reports personal fees from Astra Zeneca, GSK, Janssen, Specialised Therapeutics Australia, MSD and Merck outside the submitted work. AA reports personal fees from GSK-Tesaro and Astra Zeneca, and non-financial support from Astra Zeneca outside the submitted work. SB reports grants from Astra Zeneca, GSK and Tesaro; personal fees from Astra Zeneca, Amgen, Clovis, Genmab, Immunogen, Mersana, MSD, Merck Serono, Pfizer, Roche and Tesaro outside the submitted work. PB reports personal fees from Novartis outside the submitted work. RE reported personal fees from Astra Zeneca and Arquer Diagnostics outside the submitted work. All other authors have no conflicts of interest to disclose.