title: Trabectedin for the treatment of advanced metastatic soft tissue sarcoma: a NICE single technology appraisal.
abstract: The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of trabectedin (PharmaMar) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of advanced metastatic soft tissue sarcoma (aMSTS), as part of the Institute's single technology appraisal (STA) process. The School of Health and Related Research (ScHARR) was commissioned to act as the Evidence Review Group (ERG). This paper provides a description of the company submission, the ERG review and NICE's subsequent decisions. The ERG produced a review of the evidence for the clinical and cost effectiveness of the technology contained within the manufacturer's submission to NICE. The ERG also independently modified the manufacturer's decision analytic model to examine the impact of altering some of the key assumptions. The main evidence was derived from a single phase II randomized controlled trial (RCT) conducted in liposarcoma and leiomyosarcoma only, in which the licensed dose of trabectedin was compared with a different dose of trabectedin. Additional data were also presented from three uncontrolled phase II trials. Supplementary studies were used to represent best supportive care (BSC). The median overall survival (OS) was 13.9 months for the licensed dose of trabectedin in the main randomized controlled trial (RCT) and ranged from 9.2 months to 12.8 months in the other studies included. Supplementary studies supplied by the manufacturer, and assumed to represent BSC, had median OS of 5.9-6.6 months. The progression-free survival (PFS) rates at 6 months for trabectedin were 35.5 % in the main RCT and 24.4-29 % in the other studies included. The PFS rates at 6 months were 8-14 % for BSC. In the manufacturer's original submission to NICE, the base-case incremental cost-effectiveness ratio (ICER) of trabectedin compared with BSC was approximately £44,000 per QALY gained. After amendment of errors identified by the ERG, the ICER reported by the manufacturer increased to approximately £61,000. The ERG concluded that, despite clarifications from the manufacturer and the revisions made to the model, there was still considerable uncertainty in the ICER. The NICE Appraisal Committee (AC) gave a negative initial recommendation, although indicated that trabectedin in aMSTS met the end-of-life criteria. Subsequently, the manufacturer submitted a patient access scheme (PAS) where any cycles beyond the fifth were provided at no cost by the manufacturer. This improved the ICER to approximately £34,000 per QALY gained. The AC gave a positive recommendation, subject to the implementation of the PAS.
authors.affiliation: The School of Health and Related Research-ScHARR, The University of Sheffield, Regent Court, 30 Regent Street, Sheffield S1 4DA, UK. r.rafia@sheffield.ac.uk
authors.forename: Rachid
authors.initials: R
authors.lastname: Rafia
authors.forename: Emma
authors.initials: E
authors.lastname: Simpson
authors.forename: Matt
authors.initials: M
authors.lastname: Stevenson
authors.forename: Diana
authors.initials: D
authors.lastname: Papaioannou
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000191:economics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003362:Cost-Benefit Analysis; D003661:Decision Support Techniques; D004149:Dioxoles / Q000191:economics / Q000627:therapeutic use*; D018572:Disease-Free Survival; D006801:Humans; D008962:Models, Theoretical; D009362:Neoplasm Metastasis; D019057:Quality-Adjusted Life Years; D012509:Sarcoma / Q000188:drug therapy* / Q000191:economics / Q000473:pathology; D015996:Survival Rate; D044005:Tetrahydroisoquinolines / Q000191:economics / Q000627:therapeutic use*; D000077606:Trabectedin; D006113:United Kingdom
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin