TY - JOUR
T1 - Phase 2 study of anastrozole in patients with estrogen receptor/progesterone receptor positive recurrent low-grade endometrial stromal sarcomas: The PARAGON trial (ANZGOG 0903)
AU - Friedlander, M.
AU - Benson, C.
AU - O'Connell, R. L.
AU - Reed, N.
AU - Clamp, A.
AU - Lord, R.
AU - Millan, D.
AU - Nottley, S.
AU - Amant, F.
AU - Steer, C.
AU - Anand, A.
AU - Mileshkin, L.
AU - Beale, P.
AU - Banerjee, S.
AU - Bradshaw, N.
AU - Kelly, C.
AU - Carty, K.
AU - Divers, L.
AU - Alexander, L.
AU - Edmondson, R.
N1 - Funding 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. Funding 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. Funding Information: 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. Publisher Copyright: © 2021
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - Anastrazole
KW - Aromatase inhibitors
KW - Endometrial stromal
KW - Uterine sarcoma
KW - sarcomas
UR - http://www.scopus.com/inward/record.url?scp=85100874284&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ygyno.2021.02.016
DO - https://doi.org/10.1016/j.ygyno.2021.02.016
M3 - Article
C2 - 33608144
SN - 0090-8258
VL - 161
SP - 160
EP - 165
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 1
ER -