Systemische Therapie des hepatozellulären Karzinoms

Background: Hepatocellular carcinoma (HCC) is one of the most common and deadly malignancies worldwide. The multikinase inhibitor sorafenib has provided a survival benefit in patients with advanced HCC. Sorafenib remains the only approved agent for advanced HCC. There are only few systemic therapeutic options. No standardized second-line treatment exists for patients with progressive disease during sorafenib treatment or with intolerable side effects. Method: Novel molecular targets are under clinical development, with sobering outcomes so far. Results: Investigations of the alternative inhibitors of angiogenesis, i.e. sunitinib and brivanib, the EGFR (epidermal growth factor receptor) inhibitors erlotinib, gefitinib, lapatinib, and cetuximab as well as the MEK (mitogen- activated protein kinase) inhibitor selumetinib did not provide constructive results. Targeting c-MET with the associated inhibitor tivantinib appears to be a promising option. Overall survival and time to progression was significantly prolonged with tivantinib in patients overexpressing c-MET. Moreover, targets such as mTOR, PI3K/ Akt, and IGFR, among others, are under clinical development, though partially in early stages. The results remain to be seen. Conclusions: Systemic management of HCC remains challenging. Among HCC patients, a difficult balance between the toxicity of the treatment and the antitumoral effect can be ascertained, enabling a significant improvement of the survival of the patients. There is an urgent need for the identification of predictive and prognostic factors such as C-MET for a personalized and efficient treatment in subgroups of HCC patients.