Efficacy And Safety Analysis Of TACE-TKI-PD-1 Combination In The Treatment Of Unresectable Hepatocellular Carcinoma

Objective:The clinical data of patients with unresectable hepatocellular carcinoma in our hospital were collected and retrospectively analyzed to compare the efficacy and safety of TACE-TKI-PD-1 combined regimen and TACE regimen in the treatment of unresectable hepatocellular carcinoma.Methods : the clinical data of 168 patients with unresectable hepatocellular carcinoma diagnosed in our hospital from January 2020 to November 2022 were analyzed retrospectively.42 patients with incomplete laboratory and imaging follow-up data or treatment cycle less than 3 months were excluded.According to whether they continued to use TKI and PD-1 after TACE,the patients were divided into two groups: TACE group(n = 41);TACE-TKI-PD-1 group(n = 85).During the period of combined treatment,laboratory index reexamination and CT or MRI enhancement examination were performed at intervals of 3 to 6 weeks.Objective remission rate(ORR),disease control rate(DCR),overall survival time(OS)and incidence of treatment-related adverse events(TRAEs)were evaluated and compared between the two groups.In the evaluation of the efficacy and prognosis of different treatment regimens,they were divided into complete remission(CR),partial remission(PR),stability(SD)or progression(PD).Chi-square test was used to analyze the basic clinical data such as gender,age,history of hepatitis B(HBs Ag),alpha-fetoprotein(AFP)level,physical condition,Eastern Cooperative oncology Group Performance status,internal diameter of tumor,number of tumors,portal vein invasion,extrahepatic metastasis,ascites and liver function grade,multivariate analysis was carried out by binary Logistic regression model,and the overall survival curve was drawn by Kaplan-Meier method.Multivariate COX proportional hazard model was used to analyze the independent factors affecting DCR and OS.Results: 1.A total of 126 patients with unresectable HCC were included,with a median follow-up time of 18.0 months,and by the cut-off of follow-up,41 patients(32.7%)were in the TACE group and 85(67.3%)in the TACE-TKI-PD-1combination therapy group.The overall ORR of the TACE group was 17.1%(7/41)and the DCR was 41.4%(17/41).The overall ORR of TACE-TKI-PD-1 group was27.3%(22/85)and the overall DCR was 63.5%(55/85).ECOG score and AFP level were independent influencing factors of DCR in the TACE-TKI-PD-1 combination therapy group(P=0.031,P=0.012),respectively.2.The median OS of overall treatment was 16.0 months(95% Cl: 14.034-17.966),and the median OS of patients in the TACE group was 10.2 months(95% CI:8.876-11.124);while the median OS of the TACE-TKI-PD-1 combination group was18.8 months(95% CI: 16.764-22.236);There was significant difference in m OS between the two groups(P = 0.023).AFP level(P=0.039),treatment regimen(P=0.001),and ECOG score(P=0.019)were independent influencing factors of overall OS.ECOG score(P=0.028)was an independent influencing factor for median OS in the TACE-TKI-PD-1 combination treatment group.3.The total incidence of TRAEs in the TACE-TKI-PD-1 combination group was84.7%(72/85),and there were 28 patients with TRAEs ≥ grade 3,with an incidence of 32.9%,which were(≥ 180/110 mm Hg)hypertension(4.7%),severe diarrhea in 2(2.3%),moderate to severe hypothyroidism in 2 cases(2.3%),cardiopulmonary impairment in 2 cases(2.3%),moderate to severe neutropenia in 6 cases(7.1%),There were 6 cases of maculopapular rash,3 cases(3.5%)of increased creatinine,and3 cases of hyperthermia(3.5%).The total incidence of TRAEs in the TACE group was 73.1%(30/41),and there were 12 patients with TRAEs ≥ grade 3,with an incidence of 29.2%,which were 5 cases(12.1%)with moderate to severe neutropenia,2 cases with hyperthermia(4.8%),2 cases with moderate and severe impairment of liver function(4.8%),1 case with severe abdominal pain(2.4%),1 case with coagulation dysfunction(2.4%),and 1 case with liver abscess(2.4%).All included patients with TAREs could be relieved to grade 2 or below adverse reactions after symptomatic treatment and delayed administration,and there were no new symptoms and drug-induced deaths.Conclusions: 1.The study found that TACE combined with TKI and PD-1regimen was effective in the treatment of patients with unresectable hepatocellular carcinoma,and ORR and DCR were higher than those in the TACE group.AFP level and ECOG score were independent influencing factors for DARE in combination with TICE TKI and PD-1 DCR.2.In terms of survival benefit,the TACE combined TKI and PD-1 regimen was extended by 8.6 months compared with the TACE program m OS.Treatment regimen,ECOG score,and AFP level were independent factors of overall OS.In the subgroup analysis,ECOG score was an independent influencing factor for the TACE-TKI-PD-1combination regimen OS.3.In terms of safety,there was no significant difference in the total incidence of TRAEs and the incidence of severe adverse reactions above grade Ⅲ between TACE-TKI-PD-1 regimen and TACE regimen.Combination therapy could achieve better drug resistance and compliance.