Cost Utility of Sequential Adjuvant Trastuzumab for HER2/Neu-Positive Breast Cancer

Abstract

Trastuzumab is often featured as a prototype for future cancer treatments. It is a rationally designed biologic agent that targets the intracellular and extracellular domains of human epidermal growth factor receptor 2 (HER2). The safety and efficacy of trastuzumab were first demonstrated in patients with metastatic breast cancer as monotherapy [1,2] or in combination with chemotherapy [3–5]. More recently, trastuzumab has demonstrated efficacy as adjuvant therapy after surgery in patients with HER2positive early breast cancer. For this indication, at a cost of $50,000 for 1 year of treatment, expenditures will approach an expected $1 billion in the United States alone [6]. Thus, any economic evaluation of the use of trastuzumab in adjuvant settings deserves careful scrutiny. In this issue of Value in Health, Skedgel et al. [7] report a cost-effectiveness analysis of sequential adjuvant trastuzumab using updated 2-year results from the Herceptin Adjuvant (HERA) trial, a multinational study of 5102 women with HER2positive early breast cancer. After a median of 1 year of followup, patients who received trastuzumab had significantly greater disease-free survival compared with patients who did not receive trastuzumab (hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.43–0.67) [8]. After 2 years of follow-up, Smith et al. [9] found that the HR for disease-free survival was 0.64 (95% CI 0.54–0.76) and the HR for overall survival was 0.66 (95% CI 0.47–0.91). One year of sequential trastuzumab therapy costs approximately Canadian $50,000. Assuming that the efficacy of trastuzumab extends to 5 years, Skedgel et al. estimated the incremental cost-effectiveness ratio (ICER) to be $70,292 (95% CI $28,606–$139,657) per quality-adjusted life-year (QALY). The ICER increased to $127,862 per QALY when they assumed the duration of benefit was 3 years. These results are a departure from the conclusions of several previous cost-effectiveness analyses conducted using the 1-year results from the HERA trial and from other trials of adjuvant trastuzumab administered alongside standard chemotherapy (see Table 1) [10–21]. Given that Skedgel et al. report ICERs exceeding the often-cited thresholds of $50,000 and $100,000 per QALY, the results are unlikely to go unnoticed by decisionmakers. Therefore, a close examination of the study assumptions and methodological issues is warranted. Based on findings from previous studies, the parameters that are most likely to influence the results include (1) the cost of the treatment, (2) the duration of the benefit, and (3) the magnitude of the benefit. Cost of Treatment