Trial eligibility in advanced hepatocellular carcinoma: Does it support clinical practice in underrepresented subgroups?

Abstract

Although hepatocellular carcinoma is considered a highly lethal malignancy, recent therapeutic advances have been achieved during the last 10 years. This scenario resulted in an unprecedented improvement in survival for patients with advanced hepatocellular carcinoma, almost reaching 20-26 mo of overall survival after first-second line sequential treatment. The advent of the combination of atezolizumab with bevacizumab showed, for the first time, superiority over sorafenib with improvement in overall survival. However, first and second-line trials were correctly based on the premise that a strict selection of patients enhances the power to capture the positive effect of treatment by excluding competing risks for mortality such as liver failure, decompensated cirrhosis or other underlying medical conditions. As a result, the inclusion criteria used in clinical trials do not support the use of novel therapies in several real-world scenarios involving underrepresented subgroups, such as patients with unpreserved liver function, other comorbid conditions, a history of solid-organ transplantation, autoimmune disorders and those with a high risk of bleeding. The present text aims at discussing treatment strategies in these subgroups.

Keywords: Eligibility; Systemic therapies; End-stage; Hepatocellular carcinoma

Core Tip: The strict criteria used in clinical trials in advanced hepatocellular carcinoma have led to a scarcity of available data in a considerable proportion of patients in the real-world practice. The daily challenge of treating these underrepresented subgroups can be overcome by future clinical trials addressing special situations, collaborative studies and real-world data.