|Economic evaluation of fulvestrant as an extra step in the treatment sequence for ER-positive advanced breast cancer
|Cameron D A, Camidge D R, Oyee J, Hirsch M
This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.
The objective was to examine the cost-effectiveness of adding fulvestrant to the treatment pathways, as second- or third-line therapy, in post-menopausal women with hormone-receptor-positive breast cancer. The authors concluded that fulvestrant was an economically attractive endocrine addition to the current treatment pathways, from the perspective of the UK National Health Service. The study was based on valid methodology, although some aspects of the analysis were only partially reported. The authors’ conclusions appear to be appropriate.
Type of economic evaluation
Cost-effectiveness analysis, cost-utility analysis
The objective was to examine the cost-effectiveness of adding a hormone agent, namely fulvestrant, to the treatment pathways, in post-menopausal women, with hormone-receptor-positive advanced breast cancer (BC), who had previously received adjuvant tamoxifen.
Fulvestrant was included in the treatment pathway as either second- or third-line therapy.
For second-line therapy, the treatment sequence was non-steroidal aromatase inhibitors (NSAI, anastrozole or letrozole), fulvestrant, exemestane, docetaxel, capecitabine, and best supportive care (BSC). For third-line therapy, the sequence was NSAI, exemestane, fulvestrant, docetaxel, capecitabine, and BSC.
Both sequences were compared with the same sequence without fulvestrant; NSAI, exemestane, docetaxel, capecitabine, and BSC.
This economic evaluation was based on a Markov model with a 10-year time horizon which represented the lifetime for women with advanced BC. The authors stated that the perspective was that of the National Health Service (NHS).
The clinical data came from a systematic review of randomised controlled trials and other experimental studies. These data were supplemented with opinions from a panel of seven UK oncologists. When more than one study was retrieved, the clinical data were pooled using meta-analysis and standard statistical methods. The primary clinical endpoint was the time to progression (TTP).
Monetary benefit and utility valuations:
The utility values were derived from the panel of experts using the visual analogue scale to elicit their preferences for specific health states for advanced cancer.
Measure of benefit:
Life-years (LYs) and quality-adjusted life-years (QALYs) were used as the summary benefit measures. These were discounted at an annual rate of 3.5%.
The health service costs were those of drug acquisition, treatment administration and monitoring the underlying disease, BSC requirements, and treatment of serious adverse events requiring hospitalisations. The drug costs were derived from the British National Formulary. The resource use came from the panel of oncologists. The unit costs were derived from nationally published sources and referred to 2005 to 2006 values. All costs were in UK pounds sterling (£) and a 3.5% annual discount rate was applied.
Analysis of uncertainty:
A first-order probabilistic sensitivity analysis was undertaken involving 1,000 random simulations of the median TTP, which was the most uncertain model input. Furthermore, a series of univariate sensitivity analyses was carried out on the following model inputs: the discount rate, efficacy of treatment, different chemotherapy regimens, median TTP and number of cycles, and proportion of patients receiving docetaxel. The alternative values were either based on published reports or determined by the authors.
In the simulation for second-line fulvestrant, the expected costs per patient were £11,725 with fulvestrant and £11,424 without fulvestrant. The expected LYs were 1.86 with fulvestrant and 1.81 without fulvestrant. The expected QALYs were 1.18 with fulvestrant and 1.14 without fulvestrant. The incremental cost per LY gained with fulvestrant was £6,500 and the incremental cost per QALY gained with fulvestrant was £7,300.
In the simulation for third-line fulvestrant, the expected costs per patient were £11,055 with fulvestrant and £11,424 without fulvestrant. The expected LYs were 1.86 with fulvestrant and 1.82 without fulvestrant. The expected QALYs were 1.178 with fulvestrant and 1.142 without fulvestrant. The incremental analysis showed that fulvestrant was the dominant strategy because it was both less expensive and more effective than the treatment without fulvestrant.
The probabilistic sensitivity analysis showed that the sequence with fulvestrant as second-line therapy had a greater than 60% probability, and as third-line therapy greater than 70% probability, of being cost-effective at a threshold of £30,000 per QALY.
The deterministic sensitivity analysis did not produce wide changes in these base-case findings, except when the number of patients receiving chemotherapy on both arms was equal. In this scenario, the cost-utility ratios (per QALY) were increased to £24,000 for second-line therapy and £19,000 for third-line therapy.
The authors concluded that fulvestrant was an economically attractive endocrine addition to the current treatment pathways from the perspective of the UK NHS.
The selection of the comparators appears to have been appropriate in that the commonly used treatment pathways were considered. The authors noted that, even from a pragmatic viewpoint, the high variety of existing treatment pathways limited the ability of the model to capture all the relevant sequences.
The approach used to derive the clinical data was appropriate. The authors reported only limited details of the method and conduct of their systematic review of the literature. However, the use of a systematic literature review to identify the primary sources of evidence is a valid method. The authors acknowledged that no head-to-head comparisons were available from the literature, which was a limitation of their analysis. The opinions of a panel of experts were used to overcome the scarcity of published data. The two summary benefit measures were appropriate in capturing the impact of the treatments on patients’ health. Moreover, LYs and QALYs are comparable across diseases, thus improving the generalisability of the findings.
The analysis of costs was consistent with the perspective. A breakdown of the cost items was not presented and unit costs were reported only for the drugs. The sources of costs were appropriately selected and reflected the viewpoint of the analysis. The use of discounting was appropriate given the long-term time horizon. The cost estimates appear to have been treated deterministically and were not considered in the sensitivity analysis.
Analysis and results:
The incremental approach used to synthesise the costs and benefits was appropriate. The issue of uncertainty was addressed in the sensitivity analysis, but only focused on the clinical inputs. The results of both the base case and the sensitivity analyses were clearly presented and discussed. The authors noted some potential limitations of their analysis, which are common to other modelling studies. Also, fulvestrant led to cost savings associated with delayed or reduced use of chemotherapy as well as increased benefits, because women with advanced BC could spend a greater proportion of time on hormonal treatments, which provide a better quality of life than chemotherapies. However, this might have occurred on BSC.
The study was based on valid methodology although some aspects of the analysis were only partially reported. In general, the authors’ conclusions appear to be appropriate.
Funding received from AstraZeneca.
Cameron D A, Camidge D R, Oyee J, Hirsch M. Economic evaluation of fulvestrant as an extra step in the treatment sequence for ER-positive advanced breast cancer. British Journal of Cancer 2008; 99(12): 1984-1990
Other publications of related interest
Chia S, Gradishar W, Mauriac L, et al. Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. J Clin Oncol 2008;26:1664-70.
Howell A, Robertson JF, Abram P, et al. Comparison of fulvestrant vs tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. J Clin Oncol 2004;22:1605-13.
Hutton J, Brown R, Borowitz M, et al. A new decision model for cost-utility comparisons of chemotherapy in breast cancer. Pharmacoeconomics 1996;9:8-22.
Tobias JS. Recent advances in endocrine therapy for postmenopausal women with early breast cancer: implications for treatment and prevention. Ann Oncol 2004;15:1738-47.
Subject indexing assigned by NLM
Antineoplastic Agents /adverse effects /economics /therapeutic use; Breast Neoplasms /drug therapy /economics /metabolism /pathology; Estradiol /adverse effects /analogs & Hormone Replacement Therapy; Humans; Neoplasm Staging; Receptors, Estrogen /metabolism; Substrate Specificity; derivatives /economics /therapeutic use
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Date abstract record published