Non-Inferiority Cardiac Surveillance in HER2+ Breast Cancer

The proportion of patients who develop a cardiac event at 12 months will be estimated together with an exact 95% confidence interval. Based upon our preliminary data of early-stage HER2-positive patients treated with non-anthracycline trastuzumab-based regimens, the estimated cardiac event rate is 1.2% (95% CI 0.1–4.1%) [21 ]. The null hypothesis of the current study is that a reduced cardiotoxicity surveillance strategy is non-inferior to routine standard-of-care surveillance by a prespecified margin in the cardiac event rate of 2.9%. This non-inferiority margin corresponds to the difference between the observed cardiac event rate from our preliminary data and the upper bound of the 95% confidence interval. With 190 patients, we will have 84% power to reject the null hypothesis using a one-sided exact test with a significance level of 0.052. We will reject the null hypothesis if no more than 3 participants develop a cardiac event. If 4 or more cardiac events are observed during any point in the trial, the study will stop.