title: Randomized phase II study of lonaprisan as second-line therapy for progesterone receptor-positive breast cancer.
abstract: BACKGROUND
  The progesterone-receptor (PR) antagonists onapristone (type I) and mifepristone (type II) showed modest activity in hormone-receptor-positive breast cancer; however, onapristone in particular was associated with hepatotoxicity. Lonaprisan is a novel, type III PR antagonist that was well tolerated in phase I studies.
  
  
  METHODS
  This randomized, open-label, phase II study evaluated the efficacy and tolerability of lonaprisan as second-line endocrine therapy in postmenopausal women with stage IV, PR-positive, HER2-negative, metastatic breast cancer.
  
  
  RESULTS
  Patients received once-daily lonaprisan 25 mg (n = 34) or 100 mg (n = 34). The primary objective was not met (≥ 35% clinical benefit rate: complete/partial responses at any time until month 6 or stable disease [SD] for ≥ 6 months from start of treatment). There were no complete/partial responses. In the 25 mg and 100 mg groups, 6 of 29 patients (21%) and 2 of 29 patients (7%), respectively, had SD ≥ 6 months. Overall, 61 of 68 patients (90%) had ≥ 1 adverse event (AE), the most frequent (≥ 10% overall) being fatigue, hot flush, dyspnoea, nausea, asthenia, headache, constipation, vomiting, and decreased appetite; 33 patients had serious AEs.
  
  
  CONCLUSIONS
  Lonaprisan showed limited efficacy as second-line endocrine therapy in postmenopausal women with PR-positive metastatic breast cancer.
authors.affiliation: Department of Gynaecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. Electronic address: walter.jonat@uksh.de.
authors.forename: W
authors.initials: W
authors.lastname: Jonat
authors.affiliation: Department of Medical Oncology and Lyon Cancer Research Centre, Centre Léon Bérard, Lyon, France.
authors.forename: T
authors.initials: T
authors.lastname: Bachelot
authors.affiliation: Breast Centre St. Gallen, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Ruhstaller
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Kuss
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Reimann
authors.affiliation: Academic Division of Breast Surgery, University of Nottingham, Royal Derby Hospital, Derby, UK.
authors.forename: J F R
authors.initials: JFR
authors.lastname: Robertson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004963:Estrenes / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome; D005466:Fluorocarbons
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004963:Estrenes; D011980:Receptors, Progesterone; C419162:lonaprisan; D005466:Fluorocarbons
keywords: antiprogestin; breast cancer; lonaprisan; progesterone-receptor antagonist; progesterone-receptor positive