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The clinical effectiveness and cost-effectiveness of topotecan for small cell lung cancer: a systematic review and economic evaluation

By E. Loveman, J. Jones, D. Hartwell, A. Bird, P. Harris, K. Welch and A. Clegg

Abstract

Objectives: <br/><br/>To assess the clinical effectiveness<br/>and cost-effectiveness of topotecan as second-line<br/>treatment for small cell lung cancer (SCLC).<br/><br/>Data sources: <br/><br/>Bibliographic databases were searched<br/>from 1990 to February 2009, including the Cochrane<br/>library, MEDLINE (Ovid), EMBASE (Ovid), PREMEDLINE<br/>In-Process &amp; Other Non-Indexed Citations.<br/>Bibliographies of related papers were assessed and<br/>experts were contacted to identify additional references<br/>and the manufacturer’s submission to NICE was also<br/>searched.<br/><br/>Review methods: <br/><br/>Two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to the full text of retrieved papers using a standard form. For the clinical effectiveness review, the studies were randomised controlled trials (RCTs), which included adult participants with relapsed SCLC who responded to first-line treatment and for whom re-treatment with first-line therapy<br/>was inappropriate. The treatment was topotecan<br/>(oral or intravenous, i.v.) compared with one another,<br/>best supportive care (BSC) or other chemotherapy<br/>regimens. Outcomes included measures of response<br/>or disease progression and measures of survival. For<br/>the cost-effectiveness review studies were eligible for<br/>inclusion if they reported cost-effectiveness, cost–utility,<br/>cost–benefit or cost–consequence analyses. Data<br/>extraction and quality assessment of included studies<br/>was undertaken by one reviewer and checked by a<br/>second. Studies were synthesised through a narrative<br/>review with full tabulation of results. An independent<br/>economic model estimated the cost-effectiveness of<br/>topotecan (oral or i.v.) compared with BSC. The model<br/>used survival analysis methods to derive estimates of<br/>mean survival for patients treated with topotecan or<br/>receiving BSC alone. These were combined with quality<br/>of life (QoL) weights to derive estimates of mean<br/>quality-adjusted life expectancy for patients receiving<br/>BSC alone or topotecan plus BSC. Categories of costs<br/>included in the model included drug use, chemotherapy<br/>administration and on-treatment monitoring,<br/>management of adverse events, monitoring for disease<br/>progression and palliative care.<br/><br/>Results: <br/><br/>A total of 434 references were identified of<br/>which five were included in the clinical effectiveness<br/>review. In these trials topotecan was compared with<br/>BSC, CAV [cyclophosphamide, Adriamycin (doxorubicin)<br/>and vincristine] or amrubicin, or oral topotecan was<br/>compared with i.v. topotecan. No economic evaluations<br/>were identified. There were no statistically significant<br/>differences between groups when i.v. topotecan was<br/>compared with either CAV or oral topotecan for<br/>overall response rate (ORR). Response rate was<br/>significantly better in participants receiving i.v. amrubicin than in those receiving a low dose of i.v. topotecan (38% versus 13%, respectively, p = 0.039). There was a statistically significant benefit in favour of oral topotecan compared with BSC (HR 0.61, 95% CI 0.43 to 0.87,<br/>p = 0.01). Drug acquisition costs for four cycles of<br/>treatment were estimated at £2550 for oral topotecan<br/>and £5979 for i.v. topotecan. Non-drug treatment costs<br/>accounted for an additional £1097 for oral topotecan<br/>and £4289 for i.v. topotecan. Total costs for the<br/>modelled time horizon of 5 years were £4854 for BSC,<br/>£11,048 for oral topotecan and between £16,914 and<br/>£17,369 for i.v. topotecan (depending on assumptions<br/>regarding time progression). Life expectancy was 0.4735,<br/>0.7984 and 0.7784 years for BSC, oral topotecan and i.v.<br/>topotecan respectively. Total quality-adjusted life-years<br/>(QALYs) were 0.2247 and 0.4077, for BSC and oral<br/>topotecan respectively, resulting in an incremental costeffectiveness ratio (ICER) of £33,851 per QALY gained.<br/>Total QALYs for i.v. topotecan were between 0.3875<br/>and 0.4157 (depending on assumptions regarding time<br/>progression) resulting in an ICER between £74,074 and<br/>£65,507 per QALY gained.<br/><br/>Conclusions: <br/><br/>Topotecan appeared to be better than BSC alone in terms of improved survival, and was as effective as CAV and less favourable than i.v. amrubicin in terms of response. Oral topotecan and i.v. topotecan were similar in efficacy. Topotecan offers additional benefit over BSC, but at increased cost. ICERs for i.v. topotecan, compared with BSC, were high and suggest that it is unlikely to be a cost-effective option. The ICER for oral topotecan is at the upper extreme of the range conventionally regarded as cost-effective from an NHS decision-making perspective. Further research into the QoL of patients with relapsed SCLC could identify the impacts of disease progression and treatment response

Topics: R1
Year: 2010
OAI identifier: oai:eprints.soton.ac.uk:155431
Provided by: e-Prints Soton
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