title: Phase II randomized study of PM01183 versus topotecan in patients with platinum-resistant/refractory advanced ovarian cancer.
abstract: BACKGROUND
  PM01183 is a new compound that blocks active transcription, produces DNA breaks and apoptosis, and affects the inflammatory microenvironment. PM01183 showed strong antitumor activity in preclinical models of cisplatin-resistant epithelial ovarian cancer.
  
  
  METHODS
  Patients with platinum-resistant/refractory ovarian cancer were included in a two-stage, controlled, randomized (in a second stage), multicenter, phase II study. Primary endpoint was overall response rate (ORR) by RECIST and/or GCIG criteria. The exploratory first stage (n = 22) confirmed the activity of PM01183 as a single agent at 7.0 mg flat dose every 3 weeks (q3wk). The second stage (n = 59) was randomized and controlled with topotecan on days 1-5 q3wk or weekly (every 4 weeks, q4wk).
  
  
  RESULTS
  ORR was 23% (95% CI, 13%-37%) for 52 PM01183-treated patients. Median duration of response was 4.6 months (95% CI, 2.5-6.9 months), and 23% (95% CI, 0%-51%) of responses lasted 6 months or more. Ten of the 12 confirmed responses were reported for 33 patients with platinum-resistant disease [ORR = 30% (95% CI, 16%-49%)]; for the 29 patients treated with topotecan in the second stage, no responses were found. Median PFS for all PM01183-treated patients was 4.0 months (95% CI, 2.7-5.6 months), and 5.0 months (95% CI, 2.7-6.9 months) for patients with platinum-resistant disease. Grade 3/4 neutropenia in 85% of patients; febrile neutropenia in 21% and fatigue (grade 3 in 35%) were the principal safety findings for PM01183.
  
  
  CONCLUSIONS
  PM01183 is an active drug in platinum-resistant/refractory ovarian cancer and warrants further development. The highest activity was observed in platinum-resistant disease. Its safety profile indicates the dose should be adjusted to body surface area (mg/m2).
  EudraCT 2011-002172-16.
authors.affiliation: Department of Gynecologic Oncology, Instituto Valenciano de Oncología, Valencia.
authors.forename: A
authors.initials: A
authors.lastname: Poveda
authors.affiliation: Department of Medical Oncology, Hospital Vall d'Hebrón, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Del Campo
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard and University Claude Bernard, GINECO Group, Lyon.
authors.forename: I
authors.initials: I
authors.lastname: Ray-Coquard
authors.affiliation: Department of Medical Oncology, Paris Descartes University, GH Cochin Hôtel Dieu, Paris.
authors.forename: J
authors.initials: J
authors.lastname: Alexandre
authors.affiliation: Department of Medical Oncology, Institut Paoli Calmettes Marseille, France.
authors.forename: M
authors.initials: M
authors.lastname: Provansal
authors.affiliation: Department of Medical Oncology, Hospital Ramón y Cajal, Madrid.
authors.forename: E M
authors.initials: EM
authors.lastname: Guerra Alía
authors.affiliation: Department of Medical Oncology, Hospital Clínico Universitario San Carlos, Madrid.
authors.forename: A
authors.initials: A
authors.lastname: Casado
authors.affiliation: Department of Medical Oncology, M.D. Anderson Cancer Center, Madrid.
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez-Martin
authors.affiliation: Clinical R&D, Pharma Mar, S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Fernández
authors.affiliation: Clinical R&D, Pharma Mar, S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Rodriguez
authors.affiliation: Clinical R&D, Pharma Mar, S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Soto
authors.affiliation: Clinical R&D, Pharma Mar, S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Kahatt
authors.affiliation: Clinical R&D, Pharma Mar, S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Fernández Teruel
authors.affiliation: Clinical R&D, Pharma Mar, S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: C M
authors.initials: CM
authors.lastname: Galmarini
authors.affiliation: Clinical R&D, Pharma Mar, S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Pérez de la Haza
authors.affiliation: Clinical R&D, Pharma Mar, S.A, Colmenar Viejo, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Bohan
authors.affiliation: Department of Oncology, Institut de Cancérologie de l'Ouest, Centre René Gauducheau, Nantes-Saint Herblain, France.
authors.forename: D
authors.initials: D
authors.lastname: Berton-Rigaud
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002243:Carbolines / Q000627:therapeutic use*; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000627:therapeutic use*; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010984:Platinum / Q000627:therapeutic use*; D019772:Topotecan / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D002243:Carbolines; D006576:Heterocyclic Compounds, 4 or More Rings; C568606:PM 01183; D010984:Platinum; D019772:Topotecan
keywords: lurbinectedin; ovarian cancer; platinum resistant; topotecan