M Friedlander1, C Benson2, R L O'Connell3, N Reed4, A Clamp5, R Lord6, D Millan7, S Nottley7, F Amant8, C Steer9, A Anand10, L Mileshkin11, P Beale12, S Banerjee2, N Bradshaw3, C Kelly13, K Carty13, L Divers13, L Alexander13, R Edmondson14. 1. Royal Hospital for Women/Prince of Wales Hospital and Prince of Wales Clinical School, University of New South Wales, Sydney, Australia. Electronic address: m.friedlander@unsw.edu.au. 2. The Royal Marsden NHS Foundation Trust, London, UK. 3. NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia. 4. Beatson Oncology Centre, Gartnavel General Hospital, Glasgow, UK. 5. The Christie NHS Foundation Trust and University of Manchester, Manchester, UK. 6. The Clatterbridge Cancer Centre, Liverpool and Wirral, UK. 7. Queen Elizabeth University Hospital, Glasgow, Scotland, UK. 8. Division of Gynecologic Oncology, University Hospitals Gasthuisberg, Leuven, Belgium. 9. Border Medical Oncology, Albury-Wodonga Regional Cancer Centre, Albury, NSW, Australia. 10. Nottingham City Hospital, Nottingham, UK. 11. Peter MacCallum Cancer Centre and The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. 12. Chris O'Brien Lifehouse, Sydney, NSW, Australia. 13. Cancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, UK. 14. Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary''s Hospital, Manchester, UK; Department of Obstetrics and Gynaecology, Manchester Academic Health Science Centre, St Mary''s Hospital, Central Manchester NHS Foundation Trust; Manchester Academic Health Science Centre, Level 5, Research, Oxford Road, Manchester, UK; Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary''s Hospital, Manchester, UK; Department of Obstetrics and Gynaecology, Manchester Academic Health Science Centre, St Mary''s Hospital, Central Manchester NHS Foundation Trust; Manchester Academic Health Science Centre, Level 5, Research, Oxford Road, Manchester, UK.
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.
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.
Authors: Fionnuala Crowley; Karen A Cadoo; Sarah Chiang; Diana L Mandelker; Raazi Bajwa; Alexia Iasonos; Qin C Zhou; Kathryn M Miller; Martee L Hensley; Roisin E O'Cearbhaill Journal: Gynecol Oncol Rep Date: 2022-04-06