Title Loaded From File

Trabectedin (Yondelis; PharmaMar, Madrid, Spain) is a marine-derived antineoplastic agent first approved as a single-agent therapy for patients with soft-tissue sarcoma after failure of standard-of-care chemotherapies or who are unsuited to receive these agents. Following promising results in preclinical studies and as a single agent in phase II studies, a large randomized, multicenter, phase III trial (OVA-301) evaluated the combination of trabectedin plus PLD compared with PLD alone in patients with relapsed ovarian cancer (n = 672) and measured progression-free survival (PFS) by independent radiology review as the primary end point [9]?and?[10]. Patients included Ceftiofur in the study had recurrent or progressive disease, experienced one platinum-containing regimen and were not expected to benefit, or were ineligible or not willing to receive retreatment with platinum-based therapy. Patients were stratified by Eastern Cooperative Oncology Group (ECOG) performance score (0�C1 vs. 2) and platinum sensitivity of their disease (sensitive: PFI��6 months vs. resistant: PFI3-Methyladenine cost 0.73; 95% CI 0.56�C0.95; P = 0.017; median PFS 9.2 vs. 7.5 months). An interim analysis of overall survival (OS) was conducted with 419 events (vs. 520 required for the final analysis of OS [9]) on request from the European Medicines Agency and showed a 15% reduction in the risk of death with the combination (HR = 0.85; P = 0.092; median OS 22.4 vs. 19.5 months). Based on the PFS together with a positive trend in OS and a positive benefit/risk balance, the European Medicines Agency granted marketing authorization for trabectedin plus PLD for the treatment of patients with relapsed platinum-sensitive ovarian cancer in October 2009 [11]. A Protein Tyrosine Kinase inhibitor NICE submission was conducted for the platinum-sensitive population on the basis of the interim analysis during 2010 and it was concluded in April 2011 that there was not enough evidence to recommend trabectedin plus PLD [12]. This was primarily because the incremental cost-effectiveness ratio (ICER) for trabectedin plus PLD could be higher than ?95,000 per quality-adjusted life-year (QALY) gained compared with PLD alone. It was, however, acknowledged that the submission was based on immature data because the prespecified number of events for final analysis of OS (520 events) had not been reached [9]?and?[12].