| Hepatocellular carcinoma (HCC) is an important global health problem, and is one of the leading causes of cancer related mortality in the world. We have seen the approval of several novel targeted therapies and immunotherapies for advanced HCC. However, existing targeted therapies for advanced HCC, including immunotherapy, have only a modest impact on overall survival. Promising results from a recent phase III clinical trial of combination treatment with immunotherapy and anti-angiogenic therapy indicates this combination will now finally displace sorafenib as first-line therapy for advanced HCC9. Despite these results being considered a major breakthrough for HCC, the combination therapy only improves progression-free survival by few months over sorafenib and is associated with significant side effects. Clearly, there is an urgent need to understand the reasons for therapy-resistance to immune checkpoint blockade (ICB) in HCC. Another interesting aspect of ICB is that it can lead to prolonged durable responses, but only 20-25% of patients experience this. Thus, identifying biomarkers to accurately predict therapeutic response to ICB in HCC is currently of paramount importance. In this talk I will outline the major clinical trials which led to accelerated approval for various immunotherapies in the US, discuss major adverse events associated with immunotherapy and address future challenges the management of advanced HCC. |
