Abstract: Objective The aim of this study was to explore the clinical application value and safety of immunotherapy combined with molecular targeted drugs in the treatment of advanced hepatocellular carcinoma(HCC).Methods According to the inclusion criteria,33 patients with advanced HCC who received immunotherapy combined with molecular targeted drug therapy were included.The clinical data such as blood biochemical indexes,tumor stage,tumor imaging characteristics and previous treatment strategies of patients before medication were recorded,following up the imaging reexamination results of patients and adverse reactions during medication until the end of follow-up and loss of follow-up or the patient death.The primary endpoints were Objective response rate(ORR)and safety,and the secondary endpoint were progression-free survival(PFS)and overall survival(OS).The Kaplan-Meier method was used to analyze the clinical curative effect of patients taking medication.Results As of the last follow-up,a total of 33 patients with advanced HCC had received the combination therapy of immune drugs and molecular targeted drugs,the ORR and the disease control rate(DCR)were 24.2% and 66.7%,respectively.The median progression-free survival(mPFS)and median overall survival(mOS)were 10.9 months and 11.8 months,respectively.Treatment-related grade 1-2 adverse events and their incidences were nausea and vomiting in 2 cases(6.1%),hand-foot skin reaction in 2 cases(6.1%),reactive cutaneous capillary endothelial proliferation in 2 cases(6.1%),and fatigue in 1 case(3.0%),1 case of stomach pain(3.0%),1 case of proteinuria(3.0%),9 cases of abdominal pain(27.3%),1 case of fever(3.0%),1 case of flatulence(3.0%),hypoalbuminemia 1 case(3.0%),5 cases(15.2%)with hyperbilirubinemia,4 cases with ALT elevation(12.1%),and 10 cases with AST elevation(30.3%).Treatment-related grade 3 or higher adverse reactions and their incidences were nausea and vomiting in 1 case(3.0%),abdominal pain in 1 case(3.0%),and AST elevation in 1 case(3.0%).No treatment-related deaths were observed,and adverse events were all effectively managed.Conclusion The combined use of immune drugs and molecular targeted drugs in the treatment of advanced HCC has a high DCR and a low incidence of adverse events.It can be used as a first-line treatment option for patients with advanced HCC and is worthy of further exploration.

Key words: Hepatocellular carcinoma, Safety, Clinical efficacy, Immunotherapy, Targeted therapy