Trabectedin for the treatment of relapsed ovarian cancer.

The paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of trabectedin for the treatment of relapsed platinum-sensitive ovarian cancer, based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The submission addressed only part of the decision problem and did not provide evidence to compare trabectedin (Yondelis®, PharmaMar) and pegylated liposomal doxorubicin hydrochloride (PLDH) (Caelyx®, Schering-Plough) with key comparators. The submission's direct comparison evidence came from one reasonable-quality randomised controlled trial (RCT) of trabectedin and PLDH versus PLDH alone (ET743-OVA-301). The results of the RCT were subdivided into the entire platinum-sensitive population (> 6-month relapse after initial platinum-based chemotherapy) and partially platinum-sensitive (≥ 6- to 12-month relapse) and fully platinum-sensitive (> 12-month relapse) populations. The outcomes included were overall survival, progression-free survival measured by three types of assessor, response rates, adverse effects of treatment, health-related quality of life and cost per quality-adjusted-life-year (QALY) gained. A mixed treatment comparison (MTC) meta-analysis comparing trabectedin and PLDH with single-agent PLDH within the entire platinum-sensitive population, with paclitaxel or with topotecan also formed part of the submission. The RCT data showed that trabectedin plus PLDH compared with PLDH monotherapy had a significant effect on overall survival only within the partially platinum-sensitive subgroup. PFS results reported by the independent radiologists showed significant effects in favour of the trabectedin and PLDH arm for the entire and partially platinum-sensitive populations only. Rates of grade 3 and 4 adverse events were mostly higher in the trabectedin and PLDH arm than in the PLDH alone arm. There were several issues regarding the undertaking of the MTC, and thus the data were not considered robust. Furthermore, the ERG did not believe the MTC to be necessary to answer the decision problem. The manufacturer submitted a de novo cost-effectiveness model. The main analysis compared trabectedin in combination with PLDH versus paclitaxel, topotecan and PLDH (each as monotherapy) in the entire platinum-sensitive population, using results estimated from the MTC. Additional analyses were presented comparing trabectedin in combination with PLDH versus PLDH monotherapy using direct evidence from the OVA-301 trial for the fully, partially and entire platinum-sensitive populations. The cost per QALY gained for trabectedin in combination with PLDH versus PLDH monotherapy was estimated to be £ 70,076 in the main analysis. In the additional analyses, the cost per QALY gained for trabectedin in combination with PLDH versus PLDH monotherapy was £ 94,832, £ 43,996 and £ 31,092 for the entire, partially and fully platinum-sensitive populations, respectively. Additional work was undertaken by the ERG using patient-level data and amending some assumptions to provide a better statistical fit to the Kaplan-Meier data than the exponential distribution assumed by the manufacturer. The ERG base-case estimate of the cost per QALY of trabectedin in combination with PLDH ranged from £46,503 to £54,607 in the partially platinum-sensitive population. At the time of writing, trabectedin in combination with PLDH for the treatment of women with relapsed platinum-sensitive ovarian cancer is not recommended by NICE in the final appraisal determination.