Introduction: Trastuzumab has significantly improved survival outcomes for women with HER2 over-expressing early breast cancer. Observed short term cardiac toxicity appears reversible in the majority of cases and confidence in the long term safety is growing. Despite this, reported follow-up from adjuvant trastuzumab clinical trials does not extend beyond six years. If trastuzumab causes myocardial cell death with loss of cardiac reserve in addition to reversible myocardial stress alone, this may lead to an increased long term risk of congestive heart failure (CHF). The future incidence of this possible late cardiac toxicity remains uncertain. The aim of this study is to quantify the consequences of scenarios of late cardiac toxicity on the survival benefit and cost-effectiveness of adjuvant trastuzumab for women treated for HER2 over-expressing early breast cancer.

Methods: A cost-utility analysis was performed using a discrete-state time-dependent semi-Markov model to calculate expected costs and benefits over the lifetime of an average cohort of women with HER2 over-expressing early breast cancer when treated with or without one year of adjuvant trastuzumab. The perspective was the UK NHS. Scenarios across the full range of possibility were explored along with estimates based on expert opinion to determine the impact of possible long-term cardiac toxicity on life-expectancy, quality of life and treatment costs. Probabilistic sensitivity analysis was used to characterise uncertainly around expected outcomes.

Results: With a willingness-to-pay threshold of £30,000 (GBP) per quality adjusted life-year, trastuzumab is cost-effective if the lifetime increased risk of CHF is no more than three times the average level expected in an anthracycline treated population of women diagnosed with HER2 overexpressing early breast cancer (figure 1). Life-expectancy gains from using adjuvant trastuzumab persist even if there is a high consequent lifetime risk of congestive cardiac failure (figure 2). Conclusion: The use of adjuvant trastuzumab remains the optimal clinical and economic treatment strategy even if its use leads to moderately increased levels of cardiac disease in later life. This study supports current confidence in its cost-effectiveness and safety. Long-term follow-up after current and future adjuvant breast cancer trials is essential in to reduce the uncertainty around these estimates.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-12-02.