Setting The study setting was secondary care. The economic study was carried out in Norway.

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1 Comparing cost/utility of giving an aromatase inhibitor as monotherapy for 5 years versus sequential administration following 2-3 or 5 years of tamoxifen as adjuvant treatment for postmenopausal breast cancer Lonning P E Record Status 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. Health technology The study investigated the use of an aromatase inhibitor (i.e. anastrozole, letrozole or exemestane), given as monotherapy for 5 years, as adjuvant treatment of postmenopausal breast cancer. This intervention was compared with sequential administration of an aromatase inhibitor following 2 to 3 or 5 years of tamoxifen. Type of intervention Treatment. Economic study type Cost-effectiveness analysis and cost-utility analysis. Study population The study population comprised a hypothetical cohort of postmenopausal women aged between 55 and 75 years who had been diagnosed with breast cancer. Setting The study setting was secondary care. The economic study was carried out in Norway. Dates to which data relate The effectiveness data were derived from studies published between 1996 and The price year was Source of effectiveness data The clinical and epidemiological data used in the economic evaluation included: the number of patients on treatment in the tamoxifen monotherapy arm at different time intervals; the annual relapse rates and the percentage of patients remaining relapse-free; the reduction in contralateral breast cancer; the increased risk of hip fracture; and life expectancy. Modelling Page: 1 / 5

2 A decision analytic tree model was used to evaluate the costs and outcomes associated with each of the treatment regimens. Sources searched to identify primary studies The clinical data were derived mainly from randomised controlled trials evaluating the effectiveness of aromatase inhibitors and tamoxifen. Some evidence on relapses prevented with aromatase inhibitors was derived from the author's own assumptions. Methods used to judge relevance and validity, and for extracting data The author did not report the methods used to obtain the primary data, and therefore provided no search methods or inclusion criteria. Measure of benefits used in the economic analysis The measures of benefits used were the additional years without relapse gained and the quality-adjusted life-years (QALYs) gained. The utility values appear to have been derived from the author's own assumptions and from those reported in the published literature. Since the benefits could be generated over the lifetime of the patient, discounting was relevant and was appropriately performed at an annual rate of 3%. Direct costs The direct costs to the health care system were included in the analysis. These comprised the costs of tamoxifen, aromatase inhibitor and oral alendronate, the direct and indirect costs of a hip joint fracture and those associated with secondary hip joint replacement, and the costs of breast cancer relapse treatment. The author did not report the resource use included under these cost categories. Consequently, it is unclear which costs were included under the indirect headings. The author reported that the price of the cheapest aromatase inhibitor was used for each drug compound. The sources of all other costs were not reported. Since the costs could be incurred over the lifetime of the patient, discounting was relevant and was appropriately performed at an annual rate of 3%. The authors only reported average cost-utility ratios and did not report the average costs separately. The price year was Statistical analysis of costs The costs were treated as point estimates (i.e. the data were deterministic). Indirect Costs No productivity costs were included in the analysis. Currency The costs were converted from Norwegian kroner (NOK) to US dollars ($) using the average exchange rate for the week 25 to 29 October 2004, which was $1 = NOK Sensitivity analysis A series of one-way sensitivity analyses were undertaken. These investigated the age of the patients, quality of life estimates, the inclusion of non-breast cancer deaths, the rate of hip joint fractures, the discount rate, and the inclusion of cost-savings of relapse prevention. Estimated benefits used in the economic analysis In women aged 65 years of age, expected life expectancy was: Page: 2 / 5

3 18.53 years with anastrozole for 5 years; years with tamoxifen for 5 years followed by letrozole for 5 years; years with tamoxifen for 2 years followed by exemestane for 3 years; and years with tamoxifen for 3 years followed by exemestane for 2 years. Assuming a quality of life estimate of 0.8 after surgery, in women aged 65 years, what the author referred to as qualityyears gained with each strategy were: with anastrozole for 5 years; with tamoxifen for 5 years followed by letrozole for 5 years; with tamoxifen for 2 years followed by exemestane for 3 years; and with tamoxifen for 3 years followed by exemestane for 2 years. Cost results The costs were not reported separately from the benefits. The author reported only the average cost-utility ratios (see 'Synthesis of Costs and Benefits' section). Synthesis of costs and benefits The costs and benefits were combined using an average cost-utility ratio (i.e. the ratio of average cost to average QALYs gained). Assuming a quality of life estimate of 0.8 after surgery, in node-negative women aged 65 years, the QALYs gained with each strategy were: with anastrozole for 5 years; with tamoxifen for 5 years followed by letrozole for 5 years; with tamoxifen for 2 years followed by exemestane for 3 years; and with tamoxifen for 3 years followed by exemestane for 2 years. Assuming a quality of life estimate of 0.8 after surgery, in node-positive women aged 65 years, the QALYs gained with each strategy were: with anastrozole for 5 years; with tamoxifen for 5 years followed by letrozole for 5 years; with tamoxifen for 2 years followed by exemestane for 3 years; and with tamoxifen for 3 years followed by exemestane for 2 years. The costs and benefits were also combined using an average cost-effectiveness ratio (i.e. the ratio of the average cost to years without relapse gained). The results showed that for both node-positive and -negative women aged 65 years, the treatment regimen with the lowest cost-effectiveness ratio was tamoxifen for 3 years followed by exemestane for 2 years. The regimen with the highest cost-effectiveness ratio was tamoxifen for 5 years followed by letrozole for 5 years. The results of the sensitivity analyses showed that increasing age of the patients, the discount rate and lower quality of Page: 3 / 5

4 life estimates increased average cost-effectiveness ratios. The inclusion of non-breast cancer deaths in the model had little impact on the average cost-effectiveness ratios. Authors' conclusions While tamoxifen for 2 to 3 years followed by an aromatase inhibitor provided the lowest cost per quality-adjusted lifeyear (QALY) estimates, a further improvement in relapse-free survival of 1% if the aromatase inhibitor was given upfront provided an acceptable cost per QALY. CRD COMMENTARY - Selection of comparators An explicit justification for using tamoxifen as the comparator was given. The use of tamoxifen for 5 years was considered to be the previous 'gold' standard of adjuvant endocrine therapy. Validity of estimate of measure of effectiveness The model parameters were derived from published research and the author's own assumptions. The author reported virtually no details of the literature search conducted. It was also unclear if data from multiple studies were combined. Validity of estimate of measure of benefit The estimation of health benefit (QALYs) was derived appropriately using a decision tree analytic model. The QALYs gained were appropriately discounted. As with the measures of effectiveness, the full sources of quality of life estimates were not reported. In addition, the author presented quality-years gained in the 'Results' section, but it was unclear what these were meant to reflect, or if they had to be combined with life expectancy to generate QALYs. Validity of estimate of costs The analysis of the costs was performed from the perspective of the Norwegian health care system. Given this perspective it appears that all the relevant cost categories have been included. However, as so few details of the costing study were reported, it was unclear whether all the relevant costs had been included. The full sources used to derive the costs were not reported. Discounting was relevant, as the costs could be incurred over the lifetime of the patient, and was appropriately performed. The price year was reported, which will aid any future inflation exercises. Other issues The author reported that endocrine therapy, in general, has been found to be associated with low cost-utility estimates in early therapy as well as in the advanced setting. The issue of generalisability to other settings was addressed. Owing to the lack of information on the methods used by the author, and the assumptions made (e.g. that each drug had similar efficacy in preventing breast cancer relapse), it was unclear whether the author had presented the results selectively. Further, the author did not perform an incremental cost-utility or cost-effectiveness analysis. Consequently, the interventions were not compared against the best possible alternative. For these reasons, the conclusions of this study should be treated with some caution. The author did not report any limitations to the study. Implications of the study Given the important limitations of this study, the results should be treated with caution. Source of funding There was no financial support from industry. Bibliographic details Lonning P E. Comparing cost/utility of giving an aromatase inhibitor as monotherapy for 5 years versus sequential administration following 2-3 or 5 years of tamoxifen as adjuvant treatment for postmenopausal breast cancer. Annals of Oncology 2006; 17(2): PubMedID Page: 4 / 5

5 Powered by TCPDF ( DOI /annonc/mdj048 Other publications of related interest Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information. Hillner BE. Benefit and projected cost-effectiveness of anastrozole versus tamoxifen as initial adjuvant therapy for patients with early-stage estrogen receptor-positive breast cancer. Cancer 2004;101: Dranitsaris G, Leung P, Mather J, et al. Cost-utility analysis of second-line hormonal therapy in advanced breast cancer: a comparison of two aromatase inhibitors to megestrol acetate. Anticancer Drug 2000;11: Indexing Status Subject indexing assigned by NLM MeSH Antineoplastic Agents, Hormonal /administration & dosage /economics; Aromatase Inhibitors /administration & dosage /economics; Breast Neoplasms /drug therapy /economics /prevention & control; Chemotherapy, Adjuvant /economics; Cost-Benefit Analysis; Disease-Free Survival; Female; Humans; Models, Economic; Postmenopause; Randomized Controlled Trials as Topic; Secondary Prevention; Tamoxifen /administration & dosage /economics AccessionNumber Date bibliographic record published 31/03/2008 Date abstract record published 31/03/2008 Page: 5 / 5