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dc.contributor.authorJames, Nen_US
dc.contributor.authorPirrie, Sen_US
dc.contributor.authorPope, Aen_US
dc.contributor.authorBarton, Den_US
dc.contributor.authorAndronis, Len_US
dc.contributor.authorGoranitis, Ien_US
dc.contributor.authorCollins, Sen_US
dc.contributor.authorMcLaren, Den_US
dc.contributor.authorO'Sullivan, Jen_US
dc.contributor.authorParker, Cen_US
dc.contributor.authorPorfiri, Een_US
dc.contributor.authorStaffurth, Jen_US
dc.contributor.authorStanley, Aen_US
dc.contributor.authorWylie, Jen_US
dc.contributor.authorBeesley, Sen_US
dc.contributor.authorBirtle, Aen_US
dc.contributor.authorBrown, Jen_US
dc.contributor.authorChakraborti, Pen_US
dc.contributor.authorRussell, Men_US
dc.contributor.authorBillingham, Len_US
dc.date.accessioned2017-03-01T12:00:42Z
dc.date.issued2016-07en_US
dc.identifier.citationHealth technology assessment (Winchester, England), 2016, 20 (53), pp. 1 - 288en_US
dc.identifier.issn1366-5278en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/430
dc.identifier.eissn2046-4924en_US
dc.identifier.doi10.3310/hta20530en_US
dc.description.abstract<h4>Background</h4>Bony metastatic castration-refractory prostate cancer is associated with a poor prognosis and high morbidity. TRAPEZE was a two-by-two factorial randomised controlled trial of zoledronic acid (ZA) and strontium-89 (Sr-89), each combined with docetaxel. All have palliative benefits, are used to control bone symptoms and are used with docetaxel to prolong survival. ZA, approved on the basis of reducing skeletal-related events (SREs), is commonly combined with docetaxel in practice, although evidence of efficacy and cost-effectiveness is lacking. Sr-89, approved for controlling metastatic pain and reducing need for subsequent bone treatments, is generally palliatively used in patients unfit for chemotherapy. Phase II analysis confirmed the safety and feasibility of combining these agents. TRAPEZE aimed to determine the clinical effectiveness and cost-effectiveness of each agent.<h4>Methods</h4>Patients were randomised to receive six cycles of docetaxel plus prednisolone: alone, with ZA, with a single Sr-89 dose after cycle 6, or with both. Primary outcomes were clinical progression-free survival (CPFS: time to pain progression, SRE or death) and cost-effectiveness. Secondary outcomes were SRE-free interval (SREFI), total SREs, overall survival (OS) and quality of life (QoL). Log-rank test and Cox regression modelling were used to determine clinical effectiveness. Cost-effectiveness was assessed from the NHS perspective and expressed as cost per additional quality-adjusted life-year (QALY). An additional analysis was carried out for ZA to reflect the availability of generic ZA.<h4>Results</h4><h4>Patients</h4>757 randomised (median age 68.7 years; Eastern Cooperative Oncology Group scale score 0, 40%; 1, 52%; 2, 8%; prior radiotherapy, 45%); median prostate-specific antigen 143.78 ng/ml (interquartile range 50.8-353.9 ng/ml). Stratified log-rank analysis of CPFS was statistically non-significant for either agent (Sr-89, p = 0.11; ZA, p = 0.45). Cox regression analysis adjusted for stratification variables showed CPFS benefit for Sr-89 [hazard ratio (HR) 0.845, 95% confidence interval (CI) 0.72 to 0.99; p = 0.036] and confirmed no effect of ZA (p = 0.46). ZA showed a significant SREFI effect (HR 0.76; 95% CI 0.63 to 0.93; p = 0.008). Neither agent affected OS (Sr-89, p = 0.74; ZA, p = 0.91), but both increased total cost (vs. no ZA and no Sr-89, respectively); decreased post-trial therapies partly offset costs [net difference: Sr-89 £1341; proprietary ZA (Zometa(®), East Hanover, NJ, USA) £1319; generic ZA £251]. QoL was maintained in all trial arms; Sr-89 (0.08 additional QALYs) and ZA (0.03 additional QALYs) showed slight improvements. The resulting incremental cost-effectiveness ratio (ICER) for Sr-89 was £16,590, with £42,047 per QALY for Zometa and £8005 per QALY for generic ZA.<h4>Conclusion</h4>Strontium-89 improved CPFS, but not OS. ZA did not improve CPFS or OS but significantly improved SREFI, mostly post progression, suggesting a role as post-chemotherapy maintenance therapy. QoL was well maintained in all treatment arms, with differing patterns of care resulting from the effects of Sr-89 on time to progression and ZA on SREFI and total SREs. The addition of Sr-89 resulted in additional cost and a small positive increase in QALYs, with an ICER below the £20,000 ceiling per QALY. The additional costs and small positive QALY changes in favour of ZA resulted in ICERs of £42,047 (Zometa) and £8005 for the generic alternative; thus, generic ZA represents a cost-effective option. Additional analyses on the basis of data from the Hospital Episode Statistics data set would allow corroborating the findings of this study. Further research into the use of ZA (and other bone-targeting therapies) with newer prostate cancer therapies would be desirable.<h4>Study registration</h4>Current Controlled Trials ISRCTN12808747.<h4>Funding</h4>This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 53. See the NIHR Journals Library website for further project information.en_US
dc.formatPrinten_US
dc.format.extent1 - 288en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectHumansen_US
dc.subjectBone Neoplasmsen_US
dc.subjectStrontium Radioisotopesen_US
dc.subjectTaxoidsen_US
dc.subjectDiphosphonatesen_US
dc.subjectImidazolesen_US
dc.subjectPrednisoloneen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectDisease-Free Survivalen_US
dc.subjectQuality-Adjusted Life Yearsen_US
dc.subjectQuality of Lifeen_US
dc.subjectAgeden_US
dc.subjectMiddle Ageden_US
dc.subjectCost-Benefit Analysisen_US
dc.subjectMaleen_US
dc.subjectBone Density Conservation Agentsen_US
dc.subjectProstatic Neoplasms, Castration-Resistanten_US
dc.subjectDocetaxelen_US
dc.subjectZoledronic Aciden_US
dc.titleTRAPEZE: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of chemotherapy with zoledronic acid, strontium-89, or both, in men with bony metastatic castration-refractory prostate cancer.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.3310/hta20530en_US
rioxxterms.licenseref.startdate2016-07en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfHealth technology assessment (Winchester, England)en_US
pubs.issue53en_US
pubs.notesNo embargoen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Prostate and Bladder Cancer Research
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume20en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamProstate and Bladder Cancer Researchen_US
dc.contributor.icrauthorParker, Chrisen_US
dc.contributor.icrauthorJames, Nicholasen_US


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