Efficacy And Safety Of Targeted Immunotherapy Combined With Local Therapy In Advanced Hepatocellular Carcinoma

Background and purposes:Based on the background of the current high incidence of hepatocellular carcinoma in the world,we reviewed the clinical data of190 patients with advanced hepatocellular carcinoma who were not suitable for surgery in our hospital from January 2019 to December 2021,analyzed and discussed the efficacy and adverse reactions of immunocheckpoint inhibitor+targeted therapy+local treatment in the treatment of advanced hepatocellular carcinoma,and summarized the relevant experience of our hospital in the course of medication,It will provide certain reference for clinical doctors in the management of patients with advanced hepatocellular carcinoma,better achieve the precise and individualized comprehensive treatment of patients with hepatocellular carcinoma,maximize the survival period of patients,and improve the quality of life of patients.Methods:By collecting the clinical data of 190 patients who were diagnosed as inoperable for surgery in our hospital during the period from January2019 to December 2021,including their personal information,past medical history,liver and kidney function,blood routine,coagulation routine,liver tumor markers,routine immunity and other blood biochemical indicators,abdominal CT,abdominal color ultrasound,abdominal MR and PET-CT and other imaging examinations,and personal treatment history(including medication and local treatment).The enrolled patients were followed up by telephone and consulting hospital imaging data,and the information of imaging examination(abdominal CT,abdominal MR,etc.),adverse reactions and survival time after treatment were summarized.The patients included in the study were divided into groups according to different treatment schemes.Group A:no local treatment such as TACE,RFA,and no targeted or immunotherapy;Group B: patients who used targeted therapy combined with local treatment(TACE,RFA)alone;Group C: patients who used immunotherapy combined with local treatment(TACE,RFA)alone;Group D: patients who used targeted immunotherapy combined with local treatment(TACE,RFA).The indicators to be monitored and observed in this study are: objective response rate(ORR),disease control rate(DCR),complete response(CR),partial response(PR),disease stability(SD),disease progression(PD),median total survival(m OS),median progression-free survival(m PFS),and adverse reactions(AE).Compare the effects of different treatment schemes and the incidence of various drug-related adverse reactions.Finally,import the statistical data into SPSS 26 software for statistical analysis.Use Kaplan-Meier method to calculate the survival curve of patients in each group.The difference of the survival curve between the groups is used Log-rank test,P<0.05 is considered to have significant statistical significance.Finally,the shortterm curative effect,total survival curve,progression-free survival curve and the incidence of adverse reactions during the treatment were obtained,and the results were comprehensively analyzed to explore the efficacy and safety of the combined treatment scheme.Results:1.According to the RECIST v1.1 efficacy evaluation standard,the proportion of PR was 19.4%(12/62),SD 51.6%(32/62),and PD 29.0%(18/62)in 62 patients in Group B;Among the 28 patients in Group C,the proportion of PR was 10.7%(3/28),the proportion of SD was 46.4%(13/28),and the proportion of PD was 42.9%(12/28);Among the 60 patients in Group D,PR accounted for 53.3%(32/60),SD 40.0%(24/60)and PD 6.7%(4/60).The ORR ratio of group B,C and D was 19.4%vs10.7% vs53.3%,and P=0.000 < 0.05 was obtained by chi-square test.The ORR difference between groups was statistically significant;The proportion of DCR between the groups was 71.0% vs57.1% vs93.3%,and P was 0.001 and 0.000 respectively by chi-square test,both of which were<0.05.The difference of DCR between the groups was statistically significant.2.The survival curves of the three groups were obtained by K-M statistical analysis.It can be seen that the m OS of group A,B,C and D were 6.3 months,12.9 months,9.5 months and 18.5 months,respectively,P<0.001<0.05.The difference in m OS of patients in each group was statistically significant.The m PFS of group A,group B,group C and group D were 3.3 months,5.7 months,4.9 months and 6.9 months,respectively,P<0.001<0.05.The difference of m PFS of patients in each group was statistically significant.3.The incidence of drug-related adverse reactions(AEs)of patients in groups B,C and D was tested and P>0.05.The difference between the three groups was not statistically significant.Except for one case of grade V gastrointestinal bleeding,one case of grade V immune-associated myocarditis and one case of grade IV polymyositis in group C,most of the adverse drug reactions in the other groups were less than grade III and were within the tolerable range.Conclusions:1.Targeted and immune single drug combined with local treatment,targeted and immune combined with local treatment have shown good efficacy in the treatment of advanced primary hepatocellular carcinoma.The combination of two and three treatments can improve the ORR and DCR of patients,and can prolong the m OS and m PFS of patients,and most of them have no serious adverse reactions.2.Compared with the single targeted or single immunotherapy combined with local therapy(triple),the triple regimen has obvious advantages in ORR,DCR,OS and PFS.While increasing the proportion of ORR,DCR and prolonging m OS and m PFS,there is no significant difference in the incidence of drug-related adverse reactions,which can provide some reference for the selection of treatment methods for patients with advanced hepatocellular carcinoma.