Review article: new therapeutic interventions for advanced hepatocellular carcinoma.

Abstract

Advanced hepatocellular carcinoma (HCC) portends a poor prognosis; however recent advances in first-line and second-line treatment options should yield significant improvements in survival. To summarize the evolving landscape of treatment options for patients with advanced HCC. We reviewed published clinical trials conducted in patients with advanced HCC published in PubMed or presented at national conferences. Sorafenib was approved for treatment of unresectable HCC in 2007 and remained the only therapy with proven survival benefit in advanced HCC for several years. Lenvatinib, another tyrosine-kinase inhibitor, was recently shown to have non-inferior survival vs sorafenib and is another first-line treatment option. The tyrosine-kinase inhibitors, regorafenib and cabozantinib, were shown to significantly improve survival in the second-line setting after sorafenib failure. Ramucirumab, a VEGF inhibitor, can also improve survival in the second-line setting among patients with AFP≥400ng/dL. Phase II data highlight potential durable objective responses with immune checkpoint inhibitors, prompting conditional FDA approval of nivolumab and pembrolizumab in the second-line setting; however, recent phase III data have failed to demonstrate improved survival compared to other treatment options. Ongoing trials are evaluating combination immune checkpoint inhibitor and immune checkpoint inhibitors with tyrosine-kinase inhibitors or VEGF inhibitors in hopes of further increasing objective responses and overall survival in this patient population. There are several first-line and second-line therapeutic options available for patients with advanced HCC. Further studies are needed to determine how best to select between and sequence the growing number of therapeutic options.