Supplementary Material for: Systemic Treatment Options in Hepatocellular Carcinoma

Background: Patients with advanced hepatocellular carcinoma (HCC) typically have poor survival outcomes. Until recently, sorafenib was the only systemic therapy option available and no agents were approved after sorafenib failure. However, rapid changes are beginning to emerge in the treatment landscape of advanced HCC, with approvals of regorafenib, nivolu­mab, lenvatinib, pembrolizumab, and cabozantinib and positive phase II/III clinical trial results with other agents. Summary: Here, we provide a comprehensive overview of the clinical trial data of systemic agents that are currently approved for advanced HCC (sorafenib, regorafenib, and nivolumab), including agents recently approved in 2018 (lenvatinib, pembrolizumab, and cabozantinib) and those with recent positive phase II/III results (ramucirumab). Key features of the clinical trial design, including patient selection criteria, the use of biomarkers in HCC, and criteria for efficacy assessment, and their implications in real-world practice are discussed. Important ongoing and planned trials in advanced HCC are summarized to provide a glimpse into the future of advanced HCC treatment. From a physician’s viewpoint, the treatment algorithms for advanced HCC are undergoing significant changes, as additional and imminent approvals impact the choices of first- and second-line treatment and decisions regarding the timing of therapy initiation. With these additional choices at hand, treatment sequencing remains a complex task and should take patient selection and tolerance profiles into account. Key Messages: The treatment of advanced HCC remains challenging and complex. The rapid developments in systemic therapy for advanced HCC should be considered when determining the best choice and sequence of treatment for patients with advanced HCC.