Models to select chemotherapy, endocrine therapy or biologic agent to advance to phase III trials for advanced breast cancer

In order to improve the success rate of oncology phase III trials giving promising results in previous phase II studies, the Exponential-Gamma statistical model based on Bayesian framework is adopted and applied into the oncology drug trial for patients with the advanced breast cancer to provide insight of the likelihood that experimental regimen will provide a clinical benefit such as prolongation of survival compared with standard therapy in subsequent phase III clinical trials to make a phase III go/no go decision. The Bayesian statistical model is a hybrid Bayesian/frequentist approach where the phase III test is still in the classical (frequentist) framework, and the preceding phase II or phase III studies are used to evaluate the probability of success of such a phase III test by a Bayesian approach. The information extracted from advanced breast cancer clinical trials from 1990 to 2012 and survival data from phase II or III studies of the experimental and control regimens are used to model the survival hazard distributions for the two regimens. In addition, the existing statistical method is expanded to include two new models, the Weibull-Inverse Gamma model and Piece-wise Exponential model to derive the expected power. We study and explore retrospectively the consistence and inconsistence between calculated expected powers and the significance of actual subsequent phase III study results with endpoints of progression free survival and overall survival, and evaluate the validity of the expected power model in predicting the likelihood of successful phase III trials. Based on our experience in advanced breast cancer, an expected power of greater than 0.59 with the Exponential-Gamma model, and of greater than 0.64 with the Weibull-Inverse Gamma model provide a reasonable base to proceed to a phase III study. However, due to limitation of data, we cannot evaluate the validity of the Piece-wise Exponential method, nor provide suggestion of cut-off value of expected power for later phase III studies.Dr.P.H.Includes bibliographical referencesIncludes vitaby Xinqun Che