AFP and hepatocellular carcinoma: However, starting in 2017, six additional systemic agents were approved for advanced-stage HCC, including for first-line therapy (lenvantinib) and second-line therapy (cabozantinib, regorafenib, and ramucirumab if AFP >400 ng/mL), as well as two immune checkpoint inhibitors (ICI) for second-line therapy (nivolumab and pembrolizumab) in the accelerated approval setting [76, 77].