title: A Phase 2, Randomized, Open-Label Study of Irosustat Versus Megestrol Acetate in Advanced Endometrial Cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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. 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.
  
  
  
  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.affiliation: *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.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pautier
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Florence
authors.initials: F
authors.lastname: Joly
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Melichar
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kutarska
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Hall
authors.forename: Anna
authors.initials: A
authors.lastname: Lisyanskaya
authors.forename: Nicholas
authors.initials: N
authors.lastname: Reed
authors.forename: Ana
authors.initials: A
authors.lastname: Oaknin
authors.forename: Valerijus
authors.initials: V
authors.lastname: Ostapenko
authors.forename: Zanete
authors.initials: Z
authors.lastname: Zvirbule
authors.forename: Eric
authors.initials: E
authors.lastname: Chetaille
authors.forename: Agnès
authors.initials: A
authors.lastname: Geniaux
authors.forename: Muhammad
authors.initials: M
authors.lastname: Shoaib
authors.forename: John A
authors.initials: JA
authors.lastname: Green
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D019290:Megestrol Acetate / Q000009:adverse effects / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011960:Receptors, Estrogen / Q000378:metabolism; D013451:Sulfonic Acids / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D013451:Sulfonic Acids; C520511:irosustat; D019290:Megestrol Acetate