Pem and the Cost of Multicycle Maintenance

Klein et al.1 present a timely analysis on the cost-effectiveness of maintenance pemetrexed (Pem) in the treatment of advanced (stage IIIB/IV) non-small cell lung cancer (NSCLC), a relatively young treatment paradigm, in this issue of the Journal of Thoracic Oncology. After all, recent debate over health care reform has shed a new light on rising medical costs and their consequences for national economic health. This concern is particularly germane to cancer care for which the development of expensive novel therapeutics,2,3 limited cost controls,4 and increases in the percentage of patients receiving all types of therapy are contributing to increased health care expenditures.5 In this study, the primary analysis used the results of an international phase III trial published in 2009, which demonstrated improved progression-free and overall survival in patients receiving Pem over best supportive care alone in the maintenance setting, primarily accounted for by patients with nonsquamous histologies.6 The authors applied these results, data on adverse events, and cost estimates from a claims database as inputs to a semi-Markov model (a type of computer-based simulation of disease trajectory) to estimate life-years gained (LYGs) and the incremental cost-effectiveness ratio (ICER) of Pem maintenance therapy compared with best supportive care from the perspective of the health care payer. As secondary analyses, the authors compare Pem maintenance with the estimated ICERs for maintenance erlotinib or bevacizumab from other analyses. The authors used the recommended methods for cost-effectiveness research,7 including the use of intention-to-treat outcomes, applying a discount rate, providing sensitivity analyses to account for uncertainty, and using ICERs. Yet, in this study, the authors opted to measure outcomes in LYGs as opposed to the preferred quality-adjusted life-years; using the former measure will tend to make treatments of patients with advanced cancer more cost-effective than they actually are. This study evaluated subsets based on histology (squamous versus nonsquamous), a prespecified analysis in the original study although one for which no stratification was performed. In the absence of clinical trials directly comparing Pem to either erlotinib or bevacizumab in the maintenance setting, the authors instead relied on extrapolating data from other phase III trials, limiting the quality of the model assumptions used for the secondary analyses and making these comparisons less convincing. The key result then was the finding of the primary analysis that demonstrated an ICER of $122,371 per life-year gained in nonsquamous histology NSCLC. When all NSCLC histologies were included, the ICER increased to $205,597. So how do we use this information? To place their results into context, the authors cite the analysis by Braithwaite et al. that suggested a range for acceptable cost between $95,000 and $264,000 per LYG based on estimates of advances in health care and medical costs relative to 1950 and the benefits of insurance against the costs of noninsurance.8 Others have proposed the cost-effectiveness of renal dialysis ($120,090 per qualityadjusted life-year) as a benchmark.3 Regardless, these different ranges provide only theoretical guidance in the United States, where cost effectiveness analyses have no meaningful policy ramifications. The Food and Drug Administration has already approved Pem for maintenance therapy, but approval does not require or imply an assessment of