The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors.
Abstract Details
Trial Design and Endpoints in Hepatocellular Carcinoma: AASLD Consensus Conference
Hepatology. 2020 May 20. doi: 10.1002/hep.31327. Online ahead of print.
Josep M Llovet123, Augusto Villanueva1, Jorge A Marrero4, Myron Schwartz1, Tim Meyer5, Peter R Galle6, Riccardo Lencioni78, Tim F Greten9, Masatoshi Kudo10, Sumithra J Mandrekar11, Andrew X Zhu1213, Richard S Finn14, Lewis R Roberts15, AASLD Panel of experts on Trial Design in HCC
Author information
1Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
2Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Catalonia, Spain.
4UT Southwestern Medical Center, Dallas, Texas, United States.
5Dept Oncology, University College London Cancer Institute, London, UK.
6Dept. of Internal Medicine, Mainz University Medical Center, Mainz, Germany.
7Department of Radiology, University of Pisa School of Medicine, Pisa, Italy.
8Miami Cancer Institute, Miami, FL, United States.
9Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States.
10Department of Gastroenterology and Hepatology, Kindai University, Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
11Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States.
12Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
13Jiahui International Cancer Center, Shanghai, China.
14Geffen School of Medicine at UCLA, Los Angeles, California, United States.
15Gastroenterology & Hepatology Dept, Mayo Clinic, Rochester, MN, United States.
Abstract
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.