Trial Design And Endpoints In Hepatocellular Carcinoma: Aasld Consensus Conference

Proper trial design is critical for the success of clinical investigations. Hepatocellular carcinoma (HCC) is a complex disease that has several unique properties. In 2008, after the approval of sorafenib, a panel of experts proposed guidelines for trial design and endpoints in HCC that have been instrumental during the last decade and provided a framework to allow an homogeneous analysis of reported investigations. Since then, several phase III studies have been reported and novel challenges have emerged. A panel of experts conveyed by AASLD organized a Special Topic Conference on trial design and endpoints to address those emerging challenges. This review summarizes the analysis and conclusions of those discussions and provides novel recommendations on the selection endpoints, stratification variables and targeted populations in the complex arena of HCC. We have covered the full spectrum of the disease, from surveillance/ chemoprevention, to neoadjuvant and adjuvant trials after curative therapies, and trials in intermediate and advanced stages of HCC. We explore the prospects for incorporating biomarkers and liquid biopsy into conventional clinical trials. In addition, we address the need for obtaining tissue and blood samples in all investigations and propose novel primary endpoints such as progression free survival with restrictive rules and patient reported outcomes. This up-dated set of recommendations is timely considering the advent of more potent combination therapies in all areas of HCC management, the increase in adverse events associated with those combinations, and the evidence that several lines of effective treatments will benefit a given patient. We herein articulate a framework to facilitate capturing the efficacy of novel therapeutic strategies with the goal of improving the outcomes of patients suffering from this disease.