title: Trabectedin plus pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer: overall survival analysis.
abstract: OBJECTIVE
  Trabectedin in combination with pegylated liposomal doxorubicin (PLD) improves progression-free survival (PFS) compared to PLD alone in recurrent ovarian cancer (J Clin Oncol 2010;28:3107-14).
  
  
  METHODS
  Women, stratified by performance status (0-1 versus 2) and platinum sensitivity (platinum-free interval [PFI]<6 versus ≥ 6 months), were randomly assigned to receive PLD 30 mg/m(2) IV followed by a 3-h infusion of trabectedin 1.1mg/m(2) every 3 weeks or PLD 50mg/m(2) every 4 weeks. The study was powered to show a 33% increase in overall survival (OS) after 520 deaths had occurred.
  
  
  RESULTS
  After a median follow-up of 47.4 months, there were 522 deaths among 672 subjects. The median OS for trabectedin+PLD and PLD arms was 22.2 and 18.9 months, respectively (hazard ratio [HR]=0.86; 95% confidence interval [CI]: 0.72-1.02; p=0.0835). An unexpected but significant imbalance in the PFI favouring the PLD arm (mean PFI: PLD=13.3 months, trabectedin+PLD=10.6 months) was identified. On the basis of this finding, an unplanned hypothesis generating analysis adjusting for the PFI imbalance and other prognostic factors suggested an improvement in OS associated with the trabectedin+PLD arm (HR=0.82; 95%CI: 0.69-0.98; p=0.0285). In another unplanned exploratory analysis, the subset of patients with a PFI of 6-12 months had the largest difference in OS (HR=0.64; 95%CI: 0.47-0.86; p=0.0027).
  
  
  CONCLUSIONS
  The final OS analysis did not meet the protocol-defined criterion for statistical significance. Despite stratification on platinum sensitivity, there was an imbalance in mean platinum free interval that had an effect on OS.
authors.affiliation: Creighton University School of Medicine at St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA. Bradley.Monk@chw.edu
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Herzog
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Kaye
authors.forename: Carolyn N
authors.initials: CN
authors.lastname: Krasner
authors.forename: Jan B
authors.initials: JB
authors.lastname: Vermorken
authors.forename: Franco M
authors.initials: FM
authors.lastname: Muggia
authors.forename: Eric
authors.initials: E
authors.lastname: Pujade-Lauraine
authors.forename: Youn C
authors.initials: YC
authors.lastname: Park
authors.forename: Trilok V
authors.initials: TV
authors.lastname: Parekh
authors.forename: Andres M
authors.initials: AM
authors.lastname: Poveda
mesh_terms: D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077216:Carcinoma, Ovarian Epithelial; D004149:Dioxoles / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D016019:Survival Analysis; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage; D000077606:Trabectedin
chemical_list: D000903:Antibiotics, Antineoplastic; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D000077606:Trabectedin