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

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Description/Abstract

Objectives:

To assess the clinical effectiveness
and cost-effectiveness of topotecan as second-line
treatment for small cell lung cancer (SCLC).

Data sources:

Bibliographic databases were searched
from 1990 to February 2009, including the Cochrane
library, MEDLINE (Ovid), EMBASE (Ovid), PREMEDLINE
In-Process & Other Non-Indexed Citations.
Bibliographies of related papers were assessed and
experts were contacted to identify additional references
and the manufacturer’s submission to NICE was also
searched.

Review methods:

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
was inappropriate. The treatment was topotecan
(oral or intravenous, i.v.) compared with one another,
best supportive care (BSC) or other chemotherapy
regimens. Outcomes included measures of response
or disease progression and measures of survival. For
the cost-effectiveness review studies were eligible for
inclusion if they reported cost-effectiveness, cost–utility,
cost–benefit or cost–consequence analyses. Data
extraction and quality assessment of included studies
was undertaken by one reviewer and checked by a
second. Studies were synthesised through a narrative
review with full tabulation of results. An independent
economic model estimated the cost-effectiveness of
topotecan (oral or i.v.) compared with BSC. The model
used survival analysis methods to derive estimates of
mean survival for patients treated with topotecan or
receiving BSC alone. These were combined with quality
of life (QoL) weights to derive estimates of mean
quality-adjusted life expectancy for patients receiving
BSC alone or topotecan plus BSC. Categories of costs
included in the model included drug use, chemotherapy
administration and on-treatment monitoring,
management of adverse events, monitoring for disease
progression and palliative care.

Results:

A total of 434 references were identified of
which five were included in the clinical effectiveness
review. In these trials topotecan was compared with
BSC, CAV [cyclophosphamide, Adriamycin (doxorubicin)
and vincristine] or amrubicin, or oral topotecan was
compared with i.v. topotecan. No economic evaluations
were identified. There were no statistically significant
differences between groups when i.v. topotecan was
compared with either CAV or oral topotecan for
overall response rate (ORR). Response rate was
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,
p = 0.01). Drug acquisition costs for four cycles of
treatment were estimated at £2550 for oral topotecan
and £5979 for i.v. topotecan. Non-drug treatment costs
accounted for an additional £1097 for oral topotecan
and £4289 for i.v. topotecan. Total costs for the
modelled time horizon of 5 years were £4854 for BSC,
£11,048 for oral topotecan and between £16,914 and
£17,369 for i.v. topotecan (depending on assumptions
regarding time progression). Life expectancy was 0.4735,
0.7984 and 0.7784 years for BSC, oral topotecan and i.v.
topotecan respectively. Total quality-adjusted life-years
(QALYs) were 0.2247 and 0.4077, for BSC and oral
topotecan respectively, resulting in an incremental costeffectiveness ratio (ICER) of £33,851 per QALY gained.
Total QALYs for i.v. topotecan were between 0.3875
and 0.4157 (depending on assumptions regarding time
progression) resulting in an ICER between £74,074 and
£65,507 per QALY gained.

Conclusions:

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.