Dataset Information

Systemic Treatment Options in Hepatocellular Carcinoma.

ABSTRACT: 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, nivolu-mab, 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.

SUBMITTER: Rimassa L

PROVIDER: S-EPMC6883446 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Systemic Treatment Options in Hepatocellular Carcinoma.

Rimassa Lorenza L Pressiani Tiziana T Merle Philippe P

Liver cancer 20190529 6

<h4>Background</h4>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, nivolu-mab, lenvatinib, pembrolizumab, and cabozantinib and positive phase II/III clinical trial results with other agents.<h4>Summary</h4>H ...[more]

PMID: 31799201

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Project description:Background:Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis. First-line sorafenib has been the standard of care for a decade, but the treatment landscape is expanding. This review provides a practical overview of current and future systemic treatment options for advanced HCC and their place in clinical practice. Summary:First-line sorafenib and lenvatinib have shown to improve the survival of patients with advanced HCC. In the second line, regorafenib provides benefit for patients who previously tolerated sorafenib. Anti-PD1 antibodies, nivolumab and pembrolizumab, recently became available for second-line use in the US. Ramucirumab (for patients with ?-fetoprotein [AFP] levels ?400) and cabozantinib present potential future second-line treatment options. Combinations of systemic and locoregional treatment, such as radiofrequency ablation or selective internal radiotherapy, require further research. Precision medicine has not yet been translated into clinical practice, as the most common driver mutations (TERT promoter, CTNNB1, TP53, and ARID1A mutations) have not yet been shown to be suitable therapeutic targets. However, our growing understanding of signaling pathways and efforts in drug development are expected to pave the way for precision medicine in HCC in the future. Evaluating the place for the current and novel systemic treatment options in clinical practice can be challenging due to the diverse toxicity profiles of the treatment options and characteristics of the patient population. Sorafenib data elucidate the effect patient characteristics (such as the performance score, Child-Pugh class, AFP, etiology of the underlying disease, and level of macrovascular invasion and extrahepatic spread) may have on outcomes in advanced stages. Key Messages:Lenvatinib is expected to join sorafenib as a preferred first-line treatment in advanced HCC. In the second line, the treatment of choice, regorafenib, is soon expected to be accompanied by cabozantinib and ramucirumab in patients with AFP ?400 ng/mL, whereas nivolumab and pembrolizumab present second-line alternatives in the US.

Dataset Information

Systemic Treatment Options in Hepatocellular Carcinoma.

Publications

Systemic Treatment Options in Hepatocellular Carcinoma.

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