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A cost-utility analysis of second-line chemotherapy in metastatic breast cancer |
Launois R, Reboul-Marty J, Henry B, Bonneterre J |
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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 Second-line chemotherapy (docetaxel, paclitaxel and vinorelbine).
Study population Patients with metastatic breast cancer.
Setting The practice setting was in secondary care. The economic study was carried out in France.
Dates to which data relate Effectiveness data were based on phase II clinical trials published between 1993 and 1995. The dates for resource use were not reported. 1993 prices were used.
Source of effectiveness data The evidence of effectiveness was based on a review of previously completed studies.
Modelling A Markov model was constructed to simulate the course of patients following each of the treatments, in order to evaluate expected cost and benefits to patients. The model took into account 53 Markov states (20 for docetaxel, 19 for paclitaxel and 14 for vinorelbine) corresponding to the different clinical criteria (responses, toxicities and complications of the disease).
Outcomes assessed in the review The efficacy of different drug therapies was assessed in terms of objective response rate, duration of response, and time to progression. The side effects of therapies in terms of main toxicities: febrile neutropenia, arthralgia, severe fluid retention leading to interrupted treatment, severe fluid retention with no interruption of the treatment, and severe neurotoxicities.
Study designs and other criteria for inclusion in the review Phase II clinical trials were included in the review.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included 5 clinical trials (3 for docetaxel, 1 for paclitaxel, and 1 for vinorelbine) were included.
Methods of combining primary studies For docetaxel, pooled data from drug registration master file were used. The efficacy of the 2 other drugs was based on a single study only.
Investigation of differences between primary studies Results of the review The response rates were 57.1%, 28.9%, and 16.0% for docetaxel, paclitaxel, and vinorelbine, respectively. Response duration and time to progression were 28.0 and 21.0 weeks for docetaxel, 28.0 and 18.0 weeks for paclitaxel, and 21.0 and 12.9 weeks for vinorelbine. Febrile neutropenia occurred in 17.9%, 2.0%, and 3.0% of patients treated with docetaxel, paclitaxel, and vinorelbine, respectively. Arthralgia was found in 16.0% and severe neurotoxicities in 6.0% of patients treated with paclitaxel only. Severe fluid retention was found in docetaxel patients only, leading to interrupted treatment in 1.9% and with no interruption of the treatment in 2.9% of the patients.
Measure of benefits used in the economic analysis The following benefits were measured: Progression-free survival (PFS) and quality-adjusted progression-free survival (Q-PFS) days. Health-related quality-of-life was evaluated using a purpose built scale consisting of 6 generic and 5 disease specific dimensions. Preference values were obtained, using the standard gamble method, from 20 oncology nurses used as proxies for the patients.
Direct costs The direct medical costs were calculated using a standard cost method. A retrospective study in 5 different hospitals was conducted.153 case records from patients treated with a second-line therapy for metastatic breast cancer were examined in order to estimate the mean number of related procedures and hospital admissions. Hospital costs were allocated values from the national accounting costs by diagnosis-related groups (DRGs). Quantities of resource use were not reported separately from costs. The cost boundary adopted was hospital. Costs were not discounted.
Sensitivity analysis Response rates, median time to progression, median duration of response, adverse event rates and costs were varied in a one-way simple sensitivity analysis.
Estimated benefits used in the economic analysis For each patient, from the start of second-line chemotherapy until death, the different interventions achieved:
docetaxel:0.473 years or 173 days of PFS;
paclitaxel: 0.398 years or 145 days of PFS
vinorelbine: 0.271 years or 99 days of PFS.
After quality-adjustment the results were:
docetaxel: 125 days of Q-PFS;
paclitaxel: 103 days of Q-PFS;
vinorelbine: 68 days of Q-PFS.
Incremental PFS of docetaxel therapy was estimated to be 74 days compared to vinorelbine and 28 days compared paclitaxel. Incremental Q-PFS figures were 57 days and 22 days, respectively. Side effects of the therapies were taken into account in the model. No discounting was undertaken.
Cost results Projected costs from the start of treatment to death, after taking into account the incremental acquisition costs of taxoids, were:
docetaxel FF250,400;
paclitaxel FF251,100;
and vinorelbine FF257,200.
Total costs of docetaxel were FF6,800 lower than the costs of vinorelbine and FF700 lower than the costs of paclitaxel therapy. Costs were not discounted. Costs of adverse treatment effects were included in the total costs.
Synthesis of costs and benefits Vinorelbine and paclitaxel were dominated strategies with a lower effectiveness (progression-free days both adjusted and not adjusted for quality of life) and a greater cost than docetaxel. Using docetaxel leads to savings of approximately FF6,800 compared with the costs of using vinorelbine and FF700 compared with those of paclitaxel. When the least favourable values for the time to progression, median response time and response rate seen in phase II trials with docetaxel were used, docetaxel was still dominant over vinorelbine in all situations. However, if the same procedure was repeated with paclitaxel, the ranking of the 2 drugs was changed in three situations.
Authors' conclusions Using docetaxel brings a net benefit of 57 progression- and discomfort-free days compared with using vinorelbine, and 22 such days compared with using paclitaxel. Not only is docetaxel self-financing because of saved hospital admissions, but it produces net savings of FF6,800 compared with vinorelbine and FF700 compared with the equivalent figures for paclitaxel. The 2 competing treatment strategies are inferior to docetaxel, since overall, they are less effective than docetaxel, whereas the projected costs per patient treated are higher.
CRD COMMENTARY - Selection of comparators A justification was given for the comparators used. Vinorelbine (30 mg/m2) is the most widely used second line treatment in France. Paclitaxel (175 mg/m2) and docetaxel (100 mg/m2) are emerging as promising alternatives in France and in other markets. As the authors indicated, although vinorelbine is the most widely used drug in current French practice, this is different in other countries: mitomycin plus vinblastine is the standard treatment in the UK. You, as a user of this database, should consider whether these are widely used technologies in your setting.
Validity of estimate of measure of benefit The effectiveness model was based on 5 phase II clinical trials. No details were provided of the quality of these primary sources of evidence. The validity of quality of life related information, collected by someone acting in place of or on behalf of the patient, may be considered debatable.
Validity of estimate of costs The resource quantities were not reported separately from the costs. Adequate details of costing methods and sources of data were provided. No important cost were omitted.
Other issues The authors' conclusions seem to be justified. Sensitivity analyses were carried out to demonstrate the stability of results under varying circumstances thus enhancing generalisability to patient groups with less favourable responses to therapy. The generalisability to other countries, however, may be reduced due to selection of comparators mainly relevant in France. Also, the necessary assumption at this stage, that no difference is expected in the drugs' capacity to improve survival, needs to be assessed in future studies.
Bibliographic details Launois R, Reboul-Marty J, Henry B, Bonneterre J. A cost-utility analysis of second-line chemotherapy in metastatic breast cancer. PharmacoEconomics 1996; 10(5): 504-521 Indexing Status Subject indexing assigned by NLM MeSH Antineoplastic Agents /economics; Breast Neoplasms /drug therapy; Cost-Benefit Analysis /economics; Female; Humans; Paclitaxel /analogs & Taxoids; Vinblastine /analogs & derivatives /economics /therapeutic use; derivatives /economics /therapeutic use AccessionNumber 21996008278 Date bibliographic record published 30/11/1998 Date abstract record published 30/11/1998 |
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