Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer: outcomes in the partially platinum-sensitive (platinum-free interval 6-12 months) subpopulation of OVA-301 phase III randomized trial

Ann Oncol. 2011 Jan;22(1):39-48. doi: 10.1093/annonc/mdq352. Epub 2010 Jul 19.

Abstract

Background: OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD) over PLD alone in relapsed ovarian cancer. The optimal management of patients with partially platinum-sensitive relapse [6-12 months platinum-free interval (PFI)] is unclear.

Patients and methods: within OVA-301, we therefore now report on the outcomes for the 214 cases in this subgroup.

Results: Trabectedin/PLD resulted in a 35% risk reduction of disease progression (DP) or death [hazard ratio (HR) = 0.65, 95% confidence interval (CI), 0.45-0.92; P = 0.0152; median progression-free survival (PFS) 7.4 versus 5.5 months], and a significant 41% decrease in the risk of death (HR = 0.59; 95% CI, 0.43-0.82; P = 0.0015; median survival 23.0 versus 17.1 months). The safety of trabectedin/PLD in this subset mimicked that of the overall population. Similar proportions of patients received subsequent therapy in each arm (76% versus 77%), although patients in the trabectedin/PLD arm had a slightly lower proportion of further platinum (49% versus 55%). Importantly, patients in the trabectedin/PLD arm survived significantly longer after subsequent platinum (HR = 0.63; P = 0.0357; median 13.3 versus 9.8 months).

Conclusion: This hypothesis-generating analysis demonstrates that superior benefits with trabectedin/PLD in terms of PFS and survival in the overall population appear particularly enhanced in patients with partially sensitive disease (PFI 6-12 months).

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Dioxoles / administration & dosage
  • Dioxoles / adverse effects
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Doxorubicin / analogs & derivatives
  • Drug Administration Schedule
  • Female
  • Humans
  • Middle Aged
  • Multivariate Analysis
  • Organoplatinum Compounds / administration & dosage
  • Ovarian Neoplasms / drug therapy*
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / adverse effects
  • Recurrence
  • Tetrahydroisoquinolines / administration & dosage
  • Tetrahydroisoquinolines / adverse effects
  • Trabectedin
  • Treatment Outcome

Substances

  • Dioxoles
  • Organoplatinum Compounds
  • Tetrahydroisoquinolines
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin
  • Trabectedin