Richard S. Finn, MD, provides an overview of the systemic treatment options for advanced unresectable hepatocellular carcinoma.
Richard S. Finn, MD: When we talk about systemic treatment for advanced liver cancer, we have had several advances in the last several years. Historically, sorafenib was first approved in 2008, and it was the only systemic treatment for advanced liver cancer until around 2017, when regorafenib was approved in the second-line setting.
We are now going to concentrate on patients with newly diagnosed advanced liver cancer: patients who progressed on TACE [transarterial chemoembolization] or those who present to clinic with advanced disease. We know that sorafenib, as mentioned, was the standard of care until the approval of lenvatinib in the frontline setting. Lenvatinib, like sorafenib, is a VEGF receptor kinase inhibitor. It is multitargeted, and it has a different kinase inhibitory profile than sorafenib.
No. 1, it is potent against the VEGF receptor family, and it also has significant activity against the fibroblast growth factor receptor. These 2 things differentiate it quite a bit from sorafenib, at least scientifically. We saw in the REFLECT study that, when compared to sorafenib in this open-label study, overall survival for lenvatinib, while numerically a little longer, was noninferior by statistical design: it was not superior. It improved progression-free survival significantly, and it had an objective response rate of about 19%.
Based on these data, lenvatinib received approval for frontline therapy, and it has a little different [adverse] effect profile. While both sorafenib and lenvatinib cause GI [gastrointestinal] toxicity, such as diarrhea, anorexia, and weight loss, and both can cause hypertension, but the degree and frequency of hypertension is higher with lenvatinib. The incidence of proteinuria is more frequent and higher grade with lenvatinib vs sorafenib, which is reflecting its potent VEGF receptor activity. However, also differentiating them is the fact that hand-foot-skin reaction syndrome, or HFSR, is more common and more intense with sorafenib.
Transcript edited for clarity.