| The management of hepatocellular carcinoma (HCC) has been transformed by the emergence of multi-targeted kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICI). Recently conducted phase III trials have shown that combination therapy, which includes ICI, has surpassed sorafenib as the primary treatment choice for advanced HCC. This shift is due to the higher response rate and improved survival benefits offered by combination therapy. Currently, as the first line treatment for the advanced HCC patients atezolizumab and bevacizumab combinations or tremelimumab and durvalumab combination are recommended. For those who are not feasible to those immune check inhibitor combinations, such as underlying moderate to severe autoimmune disease or HCC recurrence after liver transplantation, TKIs such as lenvatinib or sorafenib are recommended as alternative first line options. So far, there is only evidence for second line treatment after sorafenib treatment including regorafenib, nivolumab plus ipilimumab, or pembrolizumab. The development of multiple lines of systemic therapy might lead to improving overall survival and quality of life for patients with advanced HCC. However, determining the optimal sequencing and tailoring of these therapies remains a complex task due to the heterogeneity of the disease and the limited understanding of individual patient characteristics that drive treatment responses. Examining a comprehensive set of clinical, molecular, and genetic factors might be needed to identify predictive biomarkers and treatment response indicators that can guide personalized therapeutic approaches. These approaches will provide insights into the evolving landscape of HCC treatment and contribute to the development of evidence-based guidelines for tailoring therapy in advanced HCC, which might shed light on the potential of targeted therapies, immunotherapies, and combination regimens in the management of advanced HCC. |
