Trabectedin in the treatment of metastatic soft-tissue sarcoma: cost-effectiveness and cost–utility are yet to be proved
Authors: C Blomqvist, R Johansson, M Tarkkanen
Journal: Annals of Oncology (2011)

We read with interest the study by Soini et al. [1.Soini E. Garcia San Andres B. Joensuu T. Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information.Ann Oncol. 2011; 22: 215-223Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar] regarding the cost-effectiveness of trabectedin in the treatment of metastatic soft-tissue sarcoma (STS) after failure of anthracycline and/or ifosfamide. The study addresses the use of trabectedin followed by end-stage treatment (EST) versus EST alone and concludes that trabectedin is a potentially cost-effective treatment of metastatic STS patients. The following points can be raised from their analysis: they state that 50%–80% of STS metastasizes as the true rate was 20% in the study by Fiore et al. [2.Fiore M. Casali P. Miceli R. et al.Prognostic effect of re-excision in adult soft tissue sarcoma of the extremity.Ann Surg Oncol. 2006; 13: 110-117Crossref PubMed Scopus (121) Google Scholar] with nearly 600 patients; they claim that trabectedin arrests STS growth in 40%–60% of tumors. However, in large expanded access programs, stable disease was seen in 32%–35%, partial responses in 5% and complete response in 0% to <1% of the patients [3.Demetri G.D. Blay J.Y. Schöffski P. et al.Outcomes of patients with advanced soft-tissue sarcomas treated in clinical trials vs expanded access programs: a decade of experience with single-agent trabectedin.J Clin Oncol. 2010; 28: 15sCrossref PubMed Google Scholar, 4.Samuels B. Tap W. Patel S. et al.Trabectedin (Tr) as single agent for advanced soft tissue sarcomas (STS) failing standard of care: interim analysis of 1572 patients in an expanded access program study.J Clin Oncol. 2010; 28: 15sCrossref PubMed Google Scholar]. Moreover, stable disease may not be a valid efficacy in sarcomas since many STSs have a slow growth rate [5.Blomqvist C. Tribukait B. Huuhtanen R. et al.Growth rate of lung metastases and s-phase fraction as determined by flow cytometry from the primary tumour in 25 patients with bone or soft-tissue sarcomas.Br J Cancer. 1996; 73: 1556-1559Crossref PubMed Scopus (6) Google Scholar, 6.Rööser B. Pettersson H. Alvegård T. Growth rate of pulmonary metastases from soft tissue sarcoma.Acta Oncol. 1987; 26: 189-192Crossref PubMed Scopus (12) Google Scholar]. Especially liposarcomas and leiomyosarcomas are often characterized by a protracted clinical course [7.Engström K. Bergh P. Gustafson P. et al.Liposarcoma: outcome based on the Scandinavian Sarcoma Group register.Cancer. 2008; 113: 1649-1656Crossref PubMed Scopus (50) Google Scholar, 8.Svarvar C. Böhling T. Berlin O. et al.Clinical course of nonvisceral soft tissue leiomyosarcoma in 225 patients from the Scandinavian Sarcoma Group.Cancer. 2007; 109: 282-291Crossref PubMed Scopus (95) Google Scholar]. This is of special relevance since these two histotypes are the subtypes of STS in which trabectedin may have activity. The authors simulate the use of trabectedin followed by EST versus EST alone. However, after failure of ifosfamide and/or doxorubicin, the simulated second-line EST are regimens that nowadays are rarely used after prior ifosfamide and/or doxorubicin therapy: etoposide or dacarbazine monotherapy; combination of ifosfamide, doxorubicin and dacarbazin; combination of ifosfamide and etoposide and combination of ifosfamide, etoposide and methotrexate. In recent studies with docetaxel and gemcitabine as second-line treatment, the overall survival has varied between 12 and 18 months. In their model, trabectedin followed by EST is estimated to lead to an overall survival of 21.1 versus 7.2 months with EST alone. However, in large expanded access programs with trabectedin, the overall survival was 9.1 and 11.7 months [3.Demetri G.D. Blay J.Y. Schöffski P. et al.Outcomes of patients with advanced soft-tissue sarcomas treated in clinical trials vs expanded access programs: a decade of experience with single-agent trabectedin.J Clin Oncol. 2010; 28: 15sCrossref PubMed Google Scholar, 4.Samuels B. Tap W. Patel S. et al.Trabectedin (Tr) as single agent for advanced soft tissue sarcomas (STS) failing standard of care: interim analysis of 1572 patients in an expanded access program study.J Clin Oncol. 2010; 28: 15sCrossref PubMed Google Scholar] and in the original study by Demetri et al. [9.Demetri G.D. Chawla S.P. von Mehren M. et al.Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules.J Clin Oncol. 2009; 27: 4188-4196Crossref PubMed Scopus (429) Google Scholar] focusing on unresectable/metastatic liposarcoma or leiomyosarcoma 13.9 months and 11.8 months, respectively. The latter study compared two treatment schedules: treatment once every 3 weeks with a response rate of 5.6% compared with a weekly schedule with minimal activity (response rate 1.6%). Thus the difference in survival was merely 2.1 months. In this light, the median survival benefit of trabectedin of almost 14 months compared with alternative treatments postulated by Soini et al. seems implausible. Comparative analysis of cost-effectiveness and cost–utility should preferably be based on randomized clinical trials. If randomized trials are, however, not available, the trials should at least be contemporary and be based on modern chemotherapy options with realistic estimates of survival data. The study was supported by Helsinki University Central Hospital Research Fund (EVO).