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

Citation: Gynecologic Oncology. 2021, 161(1), 160-65
Author: M. Friedlander, C. Benson, R.L. O'Connell, N. Reed, A. Clamp, R. Lord, D. Millan, S. Nottley, F. Amant, C. Steer, A. Anand, L. Mileshkin, P. Beale, S. Banerjee, N. Bradshaw, C. Kelly, K. Carty, L. Divers, L. Alexander, R. Edmondson
Abstract: 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. Keywords. Aromatase inhibitors; Anastrazole; Endometrial stromal; sarcomas; Uterine sarcoma