Patricia Pautier1, Ignace Vergote, Florence Joly, Bohuslav Melichar, Elzbieta Kutarska, Geoffrey Hall, Anna Lisyanskaya, Nicholas Reed, Ana Oaknin, Valerijus Ostapenko, Zanete Zvirbule, Eric Chetaille, Agnès Geniaux, Muhammad Shoaib, John A Green. 1. *Gustave Roussy Cancer Campus, Villejuif, France; †Leuven Cancer Institute, Leuven, Belgium; ‡Centre François Baclesse, Caen, France; §Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic; ‖Centrum Onkologii Ziemi Lubelskiej, Lublin, Poland; ¶Leeds Cancer Centre, St James University Hospital, Leeds, United Kingdom; #City Clinical Oncology Dispensary, St Petersburg, Russia; **Gartnavel General Hospital, Glasgow, United Kingdom; ††Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain; ‡‡Vilnius University Institute of Oncology, Vilnius, Lithuania; §§Oncology Centre of Latvia, Riga East University Hospital, Riga, Latvia; ‖‖Ipsen Innovation, Les Ulis, France; and ¶¶Clatterbridge Cancer Centre, University of Liverpool, Bebington, Merseyside, United Kingdom.
Abstract
OBJECTIVE:Advanced/metastatic or recurrent endometrial cancer has a poor prognosis. Malignant endometrial tissue has high steroid sulphatase (STS) activity. The aim of this study was to evaluate STS as a therapeutic target in patients with endometrial cancer. METHODS: This was a phase 2, multicenter, international, open-label, randomized (1:1), 2-arm study of the STS inhibitor oral irosustat 40 mg/d versus oral megestrol acetate 160 mg/d in women with advanced/metastatic or recurrent estrogen receptor-positive endometrial cancer. The primary end point was the proportion of patients without progression or death 6 months after start of treatment. Secondary end points included progression-free survival, time to progression, overall survival, and safety. RESULTS:Seventy-one patients were treated (36 with irosustat, 35 withmegestrol acetate). The study was prematurely stopped after futility analysis. Overall, 36.1% and 54.1% of patients receiving irosustat or megestrol acetate had not progressed or died at 6 months, respectively. There were no statistically significant differences between irosustat and megestrol acetate in response and overall survival rates. Irosustat patients had a median progression-free survival of 16 weeks (90% confidence interval, 9.0-31.4) versus 40 weeks (90% confidence interval, 16.3-64.0) in megestrol acetate patients. Treatment-related adverse events occurred in 20 (55.6%) and 13 (37.1%) patients receiving irosustat or megestrol, respectively. Most adverse events in both groups were grade 1 or 2. CONCLUSIONS: Although irosustat monotherapy did not attain a level of activity sufficient for further development in patients with advanced/recurrent endometrial cancer, this study confirms the activity of hormonal treatment (megestrol acetate) for this indication.
RCT Entities:
OBJECTIVE: Advanced/metastatic or recurrent endometrial cancer has a poor prognosis. Malignant endometrial tissue has high steroid sulphatase (STS) activity. The aim of this study was to evaluate STS as a therapeutic target in patients with endometrial cancer. METHODS: This was a phase 2, multicenter, international, open-label, randomized (1:1), 2-arm study of the STS inhibitor oral irosustat 40 mg/d versus oral megestrol acetate 160 mg/d in women with advanced/metastatic or recurrent estrogen receptor-positive endometrial cancer. The primary end point was the proportion of patients without progression or death 6 months after start of treatment. Secondary end points included progression-free survival, time to progression, overall survival, and safety. RESULTS: Seventy-one patients were treated (36 with irosustat, 35 with megestrol acetate). The study was prematurely stopped after futility analysis. Overall, 36.1% and 54.1% of patients receiving irosustat or megestrol acetate had not progressed or died at 6 months, respectively. There were no statistically significant differences between irosustat and megestrol acetate in response and overall survival rates. Irosustatpatients had a median progression-free survival of 16 weeks (90% confidence interval, 9.0-31.4) versus 40 weeks (90% confidence interval, 16.3-64.0) in megestrol acetatepatients. Treatment-related adverse events occurred in 20 (55.6%) and 13 (37.1%) patients receiving irosustat or megestrol, respectively. Most adverse events in both groups were grade 1 or 2. CONCLUSIONS: Although irosustat monotherapy did not attain a level of activity sufficient for further development in patients with advanced/recurrent endometrial cancer, this study confirms the activity of hormonal treatment (megestrol acetate) for this indication.
Authors: Gonda Konings; Linda Brentjens; Bert Delvoux; Tero Linnanen; Karlijn Cornel; Pasi Koskimies; Marlies Bongers; Roy Kruitwagen; Sofia Xanthoulea; Andrea Romano Journal: Front Pharmacol Date: 2018-09-19 Impact factor: 5.810
Authors: Mateusz Daśko; Sebastian Demkowicz; Karol Biernacki; Olga Ciupak; Witold Kozak; Maciej Masłyk; Janusz Rachon Journal: J Enzyme Inhib Med Chem Date: 2020-12 Impact factor: 5.051
Authors: Karol Biernacki; Olga Ciupak; Mateusz Daśko; Janusz Rachon; Witold Kozak; Janusz Rak; Konrad Kubiński; Maciej Masłyk; Aleksandra Martyna; Magdalena Śliwka-Kaszyńska; Joanna Wietrzyk; Marta Świtalska; Alessio Nocentini; Claudiu T Supuran; Sebastian Demkowicz Journal: J Med Chem Date: 2022-03-02 Impact factor: 7.446