Efficacy And Safety Of TACE Combined With Lenvatinib And Camrelizumab In The Treatment For Intermediate Or Advanced Hepatocellular Carcinoma

ObjectiveTo compare the clinical efficacy and safety of transarterial chemoembolization(TACE)combined with Lenvatinib and Camrelizumab(triple therapy)and TACE combined with Lenvatinib(double therapy)in the treatment for intermediate or advanced hepatocellular carcinoma(HCC),and to explore the influencing factors of efficacy,so as to provide reference for clinical application.MethodsClinical data of 70 patients in the triple therapy group and 75 patients in the double therapy group admitted to the interventional Department of our hospital for intermediate or advanced HCC from December 2019 to May 2022 were retrospectively collected and followed up until December 2022.The tumor control was evaluated according to the modified evaluation criteria for solid tumor,and the changes of AFP and PIVKA-Ⅱvalues were compared between the two groups.Objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and adverse events were compared between the two groups.Kaplan-Meier method was used to compare PFS and OS among groups,and Cox proportional hazard regression model was used to analyze the possible prognostic factors of PFS and OS.ResultsORR(84.3%,71.4%,54.3%)and DCR(98.6%,92.9%,77.1%)of the triple therapy group after 1,3 and 6 months of treatment,respectively.ORR(78.7%,54.7%,37.3%)and DCR(96.0%,80.0%,53.3%)of the double therapy group after 1,3 and 6months of treatment,respectively.The difference of ORR and DCR between two guoups at 1 month was not statistically significant(P>0.05).The ORR and DCR of the triple therapy group were higher than those of the double therapy group at 3 and 6months,and the difference was statistically significant(P<0.05).There were no differences in AFP and PIVKA-Ⅱlevels between two groups before treatment,1month,3 months and 6 months after treatment(P>0.05).In each group,there were statistically significant differences in AFP before treatment and 1 month after treatment,1 month and 3 months after treatment,and 3 months and 6 months after treatment(P<0.05).In each group,the PIVKA-Ⅱvalue of before treatment and 1month after treatment,and 1 month and 3 months after treatment had statistical significance(P<0.05);but there was no difference in PIVKA-Ⅱbetween 3 months and6 months after treatment(P>0.05).In terms of PFS and OS,m PFS was 12 months in the triple therapy group and 9months in the double therapy group,and the difference was statistically significant(χ~2=19.164,P<0.001).The m OS was 24 months in the triple therapy group and 18months in the double therapy group,and the difference was statistically significant(χ~2=29.555,P<0.001).Multivariate COX proportional risk model was used to analyze the factors affecting PFS and OS.The results showed that the independent risk factors of PFS were double therapy,maximum tumor diameter≥10cm and AFP≥400ng/ml.The independent risk factors for OS were double therapy,maximum tumor diameter≥10cm,BCLC stage C and AFP≥400ng/ml.Subgroup analysis of the factors affecting PFS and OS showed that for patients with tumor number≤3,AFP value<400ng/ml and portal vein invasion,there was no statistical significance in PFS between triple therapy and double therapy(P>0.05).In patients with tumor number>3,AFP value≥400ng/ml and no portal vein invasion,the PFS of triple therapy was better than that of double therapy(P<0.05).For patients with tumor number≤3 and portal vein main invasion,there was no statistical difference in OS between triple therapy and double therapy(P>0.05).In patients with tumor number>3 and no portal vein invasion,the OS of triple therapy was better than that of double therapy(P<0.05).In terms of adverse events,most of the patients in the two groups had gradeⅠandⅡadverse events,a small part of them had gradeⅢadverse events,and no patients had gradeⅣandⅤadverse events.There was no significant difference in the occurrence of overall gradeⅠ-Ⅲand gradeⅢadverse events between the two groups(P>0.05).Only in the incidence of RCCEP and hypothyroidism in the triple therapy group was higher than that in the double therapy group,and the difference was statistically significant(P<0.05).In the triple therapy group,m PFS and m OS in patients with RCCEP or hypothyroidism were higher than those without RCCEP or hypothyroidism(15 vs 11 months;26 vs 23 months),and the differences were statistically significant(P<0.05).Conclusion1.TACE combined with Lenvatinib and Camrelizumab(triple therapy)has synergistic anti-tumor effect in the treatment for intermediate or advanced HCC,which can significantly improve the efficacy and has good safety,and is a recommended"TACE+"treatment regimen for intermediate or advanced HCC.2.The efficacy of tumor therapy is closely related to tumor staging,liver storage function and patient’s systemic condition.3.PD-1 inhibitor in triple therapy is a long course of treatment,and long-term benefits should be used as the main evaluation criteria.4.For patients with intermediate or advanced HCC with tumor number>3,AFP value≥400ng/ml,and no portal vein invasion,the clinical efficacy of triple therapy is better.5.Triple therapy can better activate the immune response,and immune-related complications may occur in some patients,but it is often suggested to have better antitumor efficacy,and the degree is mild.