**4. Conclusion**

Current data of systemic therapy in advanced stage/unresectable or failure to locoregional therapy HCC shown efficacy and safety profile of multiple targeting agents such as Lenvatinib, regorafenib, cabozantinib and ramucirumab in addition to standard treatment with sorafenib. New emerging current standard of care in advanced HCC is change to combination therapy with Bevacizumab plus atezolizumab as first line therapy due to improvement of progression free survival and with overall survival. The increase in available multiple targeting agents and immune checkpoint blockade will benefit in many patients. Sequential therapy and drug selection will become more challenging as **Figure 1**. New strategies of systemic therapy with new combination therapy are needed to explore.

**Figure 1.**

*Possible sequential systemic therapy for advanced stage/unresectable or failure to locoregional treatment HCC, hepatocellular carcinoma; 2 L, second line; 3 L, third line; AFP, alpha-fetoprotein.*
