Trastuzumab for all? A decision analysis examining tradeoffs between efficacy and cardiac toxicity of adjuvant therapy in HER2 positive breast cancer

Abstract

6022 Background: Early results from three randomized trials showed that adjuvant trastuzumab (T) results in significant reduction in recurrence rates in high risk HER2 positive breast cancer patients (pts). However, the long term survival benefits and the balance of risk and benefit of adjuvant T in pts with lower risk of cancer recurrence and a higher risk of cardiac toxicity (elderly and pre-existing heart disease) remain undetermined. Methods: We evaluated these tradeoffs through a Markov state transition decision analytic model to simulate the survival benefits in a variety of subpopulations of HER2 positive cancer pts. Efficacy and cardiac toxicity of T were based on B-31 and N9831 trials. Outcomes were expressed in quality adjusted life years (QALYs) and 10 year survival rates. We explored a number of prototypic scenarios that varied in age, risk of cancer recurrence, and cardiac toxicity rates. Our base case focused on a 50 year-old, 2 cm, node positive, ER/PR negative pt with a 6% cumulative risk of cardiac toxicity. Results: Survival rates and the cardiac death rates for the base case and a hypothetical elderly pt with low risk of cancer recurrence are illustrated in the table . One-way sensitivity analyses on the base case, across a wide range of values for age (50–80); hazard ratio for T efficacy (0.48 to 0.95); annual cancer recurrence risk (0.5–5%) and cardiac toxicity (4–60%) demonstrated that adjuvant T was the more effective strategy. Conclusions: The addition of T in HER2 positive cancer is more effective than standard chemotherapy alone in most cases, including elderly pts with node negative disease and those with increased risk of cardiac toxicity. However, the incremental benefit decreases with advancing age, higher risk of cardiac toxicity and in pts with lower risk of recurrence. This model is a useful clinical tool to quantify risks and benefits of adjuvant T and in predicting long term survival in different subpopulations of HER2 positive breast cancer pts. [Table: see text] No significant financial relationships to disclose.