Analysis Of The Efficacy And Safety Of Immune Checkpoint Inhibitors Combined With Anti-angiogenesis Targeted Drugs Compared To Sorafenib As First-line Treatment For Unresectable Hepatocellular Carcinom

Objective: Hepatocellular carcinoma is a common and fatal malignant tumor in the world.Immune checkpoint inhibitors combined with anti-angiogenesis targeted drugs have made great progress in the treatment of advanced hepatocellular carcinoma.This study compares the efficacy and safety of immune checkpoint inhibitors combined with anti-angiogenesis targeted drugs and sorafenib in the first-line treatment of unresectable intermediate and advanced hepatocellular carcinoma patients,aiming to provide reference for the clinical application of immune checkpoint inhibitors combined with anti-angiogenesis targeted drugs.Methods: The prospective analysis of 58 unresectable patients with intermediate to advanced hepatocellular carcinoma admitted to the Department of Hepatic Surgery of Provincial Hospital Affiliated to Anhui Medical University from May 1,2019 to December 31,2021 was conducted.37 patients were treated with an immune checkpoint inhibitor combined with an anti-angiogenesis-targeted drug(combination group)as the treatment regimen,and 21 patients were treated with sorafenib(control group)as the treatment regimen.The efficacy and safety of the two groups were evaluated according to the response evaluation criteria in solid tumors version 1.1(RECIST 1.1)and the common terminology criteria for adverse events version 5.0(CTCAE 5.0).The primary observations of the study were overall survival(OS),progression-free survival(PFS)and adverse events,and the secondary observations of the study were objective response rate(ORR)and disease control rate(DCR).Results:The results of the study showed that the median OS was significantly longer in the combination group than in the control group(27.0 months vs 11.4 months,respectively;p = 0.04).The median PFS was also longer in the combination group than in the control group(12.0 months vs 6.0 months,respectively;p = 0.02).The DCR of the combination group was higher than that of the control group(51.3% vs28.6%,respectively;p = 0.09),and the ORR of the combination group was also higher than that of the control group(18.9% vs 9.5%,respectively;p = 0.34).Multifactorial Cox regression analysis showed that target lesion sum diameter and albumin were independent prognostic factors for PFS(HR = 2.67;95%CI = 1.05 to 6.79;p = 0.04 and HR = 0.36;95%CI = 0.14 to 0.92;p = 0.03,respectively),and free triiodothyronine was an independent prognostic factor for OS(HR = 0.42;95%CI =0.17 to 0.96;p = 0.04).Treatment-related adverse events occurred in all patients within both study groups.Grade 3 or higher treatment-related adverse events occurred in 51%and 43% in the combination and control groups,respectively.However,this difference was not statistically significant(p = 0.53).Most of the grade 3-4 adverse events in both groups could be improved by suspending the treatment regimen,adjusting the treatment dose and providing symptomatic support treatment,and were generally safe and manageable.The overall safety of the combination group can be monitored and controlled.Conclusions: The results from the study showed that combination of checkpoint inhibitors and anti-angiogenesis targeted drugs had better efficacy for unresectable hepatocellular carcinoma patients with relatively controllable adverse events and good safety.