Letter to the Editor

Re: Xie J, Diener M, De G, et al. Budget impact analysis of everolimus for the treatment of hormone receptor positive, human epidermal growth factor receptor-2 negative (HER2−) advanced breast cancer in the United States. J Med Econ 2014;16(2):278-88.

Dear Editor

This commentary responds to the article by Xie et al.1, who conducted a budget impact analysis (BIA) of everolimus as the first and second treatment option after letrozole or anastrozole (L/A) failure, for post-menopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2−) advanced breast cancer (ABC).

The study by Xie et al.1 builds upon the interim results of the phase 3 randomized controlled trial referred to as BOLERO-22. These results favored the combination of everolimus and exemestane over exemestane alone, in regard to the median progression free survival, causing the approval of the combination by the United States (US) Food and Drug Administration (FDA) in 2012. In the attempt to provide the necessary and required evidence for payers to make informed coverage decisions, Xie et al.1 assessed the economic (budgetary) impact, to a US payer, of listing everolimus as a first and second treatment option after L/A in post-menopausal women HER2− ABC.

As part of the sensitivity analysis of the BIA, Xie et al.1 estimated the cost of the management of grade 3–4 adverse events for the combination everolimus and exemestane (US$847) and exemestane alone (US$141) (see page 283, Xie et al.1). While we value the design of the BIA, we have reservations about the above-mentioned estimates used in the sensitivity analysis.

Firstly, the authors state the following ‘only grade 3/4 levels adverse events with at least 5% incidence in any arm of the BOLERO-2 trial (stomatitis and anemia) were considered’1. The authors did not provide any rationale for considering only 5% incidence of grade 3/4 levels adverse events. We would have expected to see all grade 3/4 levels adverse events included in the analysis. It is our understanding that this approach under-estimates the economic impact of the potential addition of everolimus to a formulary.

Secondly, let us presume there is a rationale for considering only adverse events for which the incidence is at least 5%. This would imply that the cost of the management of adverse events should be US$0 in the exemestane arm as the incidence of each adverse event was 1% and, therefore, should not be considered (see Table 1). Under these circumstances, using the current costs of the management of the adverse events would under-estimate the economic impact of covering everolimus.

Table 1. Incidence of common grade 3/4 adverse events of BOLERO-2.

Adverse events	Treatment arm 0	Treatment arm 1
Stomatitis	1%	8%*
Anemia	1%	6%*
Dyspnea	1%	4%
Hyperglycemia	1%	4%
Fatigue	1%	4%
Pneumonitis	0%	3%

*Incidence of grade 3/4 adverse events superior or equal to 5%; Treatment arm 0: exemestane; Treatment arm 1: everolimus and exemestane.

We suggest that Xie et al.1 provide a rationale for excluding grade 3/4 levels of adverse events, with less than 5% incidence, of the sensitivity analysis conducted in their BIA. In addition, we would be interested in receiving some clarifications about the steps that led the authors to estimate a cost of US$141 for exemestane alone, when considering only grade 3/4 levels of adverse events with at least 5% incidence.

Transparency

Declaration of funding

This letter was not funded.

Declaration of financial/other relationships

The authors have no relevant financial or other relationships to disclose.