Do the Large Benefits Justify the Large Costs of Adjuvant Breast Cancer Trastuzumab

In the 1990s, breast cancer mortality rates in middle-age women declined by 25% to 30% in the United States. This decline was primarily due to adjuvant hormonal therapy or chemotherapies. The efficacy of adjuvant therapy was determined in randomized trials to form a rich evidence base and the rapid adoption of this knowledge by cancer providers into routine care. Separate from the effectiveness assessments, the vast majority of these interventions also met typical criteria for acceptable cost effectiveness—as defined by the WHO as interventions with a cost-effectiveness ratio less than the per capita gross domestic product. Since 2000, innovative approaches to adjuvant therapy for breast cancer patients have emerged using a new class of hormonal therapies(aromatase inhibitors),newschedulesofdeliveringchemotherapy (dose-dense therapy), and targeted treatments at specific newly identified features of the breast cancer cells (trastuzumab). Unfortunately, the financial price of these new interventions has been an increase in costs of fiveto 10-fold compared with the preceding standard approach. Such marked increased adjuvant therapy costs are a microcosm of broader trends pushing up health care costs in the United States—patients continue to want the newest (and most expensive) drugs and medical devices, patients are relatively protected from the prices of new agents (excluding potential copayments), the US Food and Drug Administration does not regulate or negotiate prices as part of its approval process for new agents, and Medicare does not consider costs in any of its reimbursement decisions. Given this perfect storm environment in the United States, cost-effectiveness analyses that attempt to estimate the incremental costs per additional year of survival may be highly important in deciding whether we can justify these new treatments compared with other uses of the same or additional health care dollars. In this issue of the Journal of Clinical Oncology, two reports (Kurian et al and Liberato et al) assess the projected long-term costs and benefits of adjuvant trastuzumab for patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer. Does the unprecedented reduction by about one half in the risk of breast cancer recurrences represent a good value given that the drug costs alone for 1 year of trastuzumab exceed the average lifetime costs of the typical breast cancer patient of 10 to 15 years ago? First, we discuss the methods used. Both reports were conducted without financial support from manufacturers of trastuzumab. Each used a Markov model to track the long-term natural history of hypothetical cohorts of women with node-positive, HER2-positive breast cancer similar to the entry criteria of National Surgical Adjuvant Breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 trials. Each attempted to take a societal perspective but in their conduct actually took a health care insurer perspective because only direct health care costs were considered. Given that the median follow-up was only 2 years, it is not surprising that the reports differed in the assumptions used for the benefits and risks in subsequent years. Tables 1 and 2 summarize and compare important differences. The two most important factors were the duration of trastuzumab’s benefit and the annual risk of systemic recurrence. The assumption of Liberato et al that the benefit of trastuzumab would persist only for 5 years is well supported by the Early Breast Cancer Trialists’ Meta-Analysis. In contrast, the assumption of Kurian et al that a one-third decline in benefit in years 3 to 5 and an additional but persistent benefit from years 6 to 10 to us appears excessively optimistic. The reports differed slightly in the risk of systemic recurrences beyond 5 years but this had little impact on the results.