Annals of Oncology Advance Access originally published online on October 16, 2006
Annals of Oncology 2007 18(2):393; doi:10.1093/annonc/mdl351
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© 2007 European Society for Medical Oncology
letters to the editor |
The cost-effectiveness of bisphosphonates in metastatic breast cancer: letter to the editor in response to Botteman et al. 2006
We agree with the main conclusion of the recent paper by Botteman et al. [1] entitled ‘the cost effectiveness of bisphosphonates in the management of breast cancer patients with bone metastases’ that bisphosphonate use in patients with breast cancer is cost-effective. However, we consider that the paper contains key methodological problems that result in biased conclusions on the cost-effectiveness of zoledronic acid compared with other bisphosphonates. Of interest, another group recently compared the cost-effectiveness of oral ibandronate, i.v. zoledronic acid and generic pamidronate also in the metastatic breast cancer setting and came to a different conclusion on the most cost-effective bisphosphonate [2].In the absence of direct comparative data, all evidence on outcomes within an economic evaluation should be obtained from a systematic review of published literature. Where several sources of data exist, synthesis of these data through a meta-analysis should be considered [3]. Botteman's model [1] indirectly compares the efficacy of each treatment to a pooled estimate for placebo to provide an overall estimate of treatment effect. The methods for identifying and assessing the quality and validity of the trials are not reported and are subject to bias. For example, the data for zoledronic acid in the model [1] are drawn from a single study carried out in Japanese patients, while the impact of using alternative published studies has not been comprehensively explored in the sensitivity analysis. The model does not consider the impact of adverse events: the incidence of osteonecrosis of the jaw is estimated to be between 0.6% and 1.1% in patients with metastatic breast cancer receiving i.v. amino-bisphosphonates (zoledronic acid or pamidronate) [4]. These agents are also associated with a higher risk of renal impairment as compared with other bisphosphonates [5]. The cost of managing these adverse events and the resulting impact on patients' quality of life should therefore be considered in the economic evaluation. Furthermore, the original clodronate versus placebo trials were conducted in patients with more progressive disease than in the later trials with pamidronate and zoledronic acid.
Several assumptions used within the economic model are totally unsupported by clinical evidence, including the statement that the quality of life benefits of oral clodronate would be half as large as with other therapies. Furthermore, the assumptions on discontinuation rates are not consistent between treatments, with i.v. treatments and oral ibandronate using rates of adverse events (AE)-related discontinuations only, while those for oral clodronate are on the basis of all discontinuations with assumptions beyond the clinical trial setting. For example, the assumed monthly discontinuation rate for oral ibandronate of 0.95% is 20 times lower than that used for oral clodronate (20.1 %), while total discontinuations in the i.v. bisphosphonate and oral ibandronate studies >1–2 years ranged from 27% to 42% (excluding deaths).
The key methodological weaknesses of the economic evaluation is the lack of direct evidence to compare all treatments within a single study, thereby requiring the numerous inferences on the basis of limited clinical data. Nevertheless, it is important to remember that all bisphosphonate therapies are cost-effective relative to no treatment.
1 Senior Medical Advisor
2 Medical Information Officer, Schering Health Care Ltd, The Brow, Burgess Hill, West Sussex RHI5 9NE
3 WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX
* (E-mail: bsouberbielle{at}schering.co.uk)
References
1. Botteman M, Barghout V, Stephens J, et al. (2006) Cost effectiveness of bisphosphonates in the management of breast cancer patients with bone metastases. Ann Oncol 17:1072–1082.
2. De Cock E, Hutton J, Canney P, et al. (2005) Cost effectiveness of oral ibandronate compares with i.v. zoledronic acid or i.v. generic pamidronate in breast cancer patients with metastatic bone disease undergoing i.v. chemotherapy. Support Care Cancer 13:959–960.[CrossRef][Web of Science][Medline]
3. National Institute for Health and Clinical Excellence. Guide to the methods of technology appraisal [online] April 2004; http://www.nice.org.uk/page.aspx?o=201973 (15 September 2006, date last accessed).
4. Poznak C. (2004) The phenomenon of osteonecrosis of the jaw in patients with metastatic breast cancer. Cancer Invest 24:110–112.[CrossRef]
5. Balla J. (2005) The issue of renal safety of Zoledronic acid from a nephrologist's point of view. Oncologist 10:306–308.
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