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Abstract:
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There has been a shift in the conduct of early-stage breast cancer trials in recent years. Instead of long adjuvant trials with survival time as the efficacy endpoint, researchers are conducting shorter neoadjuvant trials with pathological complete response (pCR) at time of surgery as the efficacy endpoint. The FDA currently accepts these trials for drug approval on condition that long-term data is collected to eventually prove survival efficacy, either in conjunction with, or subsequent to, the neoadjuvant trial. To calculate an appropriate sample size for a confirmatory adjuvant trial based upon data from a neoadjuvant trial, it is necessary to relate the effect size of the binary neoadjuvant pCR endpoint with a survival end point effect size. We propose a parametric model for survival time using the neoadjuvant pCR rates, as well as an estimated benefit of achieving pCR to determine the treatment effect size. Through simulation we determine the appropriate sample size to achieve 80% power under a range of parameter values. These results can be used in powering confirmatory adjuvant trials in early-stage breast cancer.
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