A Bayesian hierarchical mixture cure modelling framework to utilize multiple survival datasets for long-term survivorship estimates: A case study from previously untreated metastatic melanoma

Abstract: Time to an event of interest over a lifetime is a central measure of the clinical benefit of an intervention used in a health technology assessment (HTA). Within the same trial, multiple end-points may also be considered. For example, overall and progression-free survival time for different drugs in oncology studies. A common challenge is when an intervention is only effective for some proportion of the population who are not clinically identifiable. Therefore, latent group membership as well as separate survival models for identified groups need to be estimated. However, follow-up in trials may be relatively short leading to substantial censoring. We present a general Bayesian hierarchical framework that can handle this complexity by exploiting the similarity of cure fractions between end-points; accounting for the correlation between them and improving the extrapolation beyond the observed data. Assuming exchangeability between cure fractions facilitates the borrowing of information between end-points. We undertake a comprehensive simulation study to evaluate the model performance under different scenarios. We also show the benefits of using our approach with a motivating example, the CheckMate 067 phase 3 trial consisting of patients with metastatic melanoma treated with first line therapy.