Safety And Clinical Efficacy Of PD-1 Inhibitor Combined With Targeted Drugs In The Treatment Of Advanced Primary Liver Cancer

Objective:The purpose of this study is to retrospectively evaluate the clinical data of patients with advanced primary liver cancer in our hospital,analyze and discuss the safety and clinical efficacy of programmed death receptor-1(PD-1)inhibitor combined with tyrosine kinase inhibitor(TKI)targeted drug therapy in patients with advanced primary liver cancer,and summarize the relevant experience from our hospital,in order to provide some reference for clinicians to strengthen the whole process management of patients with advanced primary liver cancer,to better perform the individualized and accurate comprehensive treatment of patients with advanced liver cancer,and maximize the quality of life and survival time of patients.Methods:Data from total of 172 patients with advanced primary liver cancer diagnosed in our department from July 2018 to December 2020 were collected.The data collection included the patient’s personal information,medical history,routine blood in the urine,liver and kidney function,blood clotting tests,liver tumor markers and other blood biochemical indexes,image information,medical history,curative effect,adverse reaction and survival status and other information,etc.The follow up was conducted through the ways of medical office system query and telephone.According to different treatment regiments,the patients included in this study were then grouped into 4 groups,Patients without treatment(group A),patients receiving only targeted therapy(group B),patients receiving only immunotherapy(group C),and patients receiving combined targeted immunotherapy(group D)The indicators to be observed in this study were formulated as: complete response(CR),partial response(PR),stability(SD),progression(PD),objective response rate(ORR),disease control rate(DCR),median overall survival(MOS),and median progression-free survival(MPFS).The therapeutic effect and adverse reactions were observed in each group.Finally,the statistical data were imported into SPSS26 software for statistical analysis,and Kaplan--Meier method was used to calculate the survival curves of each group.The difference of survival curves among each group was tested by Log-rank test,and P<0.05 was considered statistically significant.Finally,the short-term efficacy,overall survival curve,progression-free survival curve and the incidence of adverse reactions during treatment were obtained for each group,and then the results were comprehensively analyzed to discuss the efficacy and safety of the combination regimen.Results:1.According to the 2010 version of m RECIST efficacy evaluation criteria,in the targeted monotherapy group of 45 patients(group B),the proportion of PR was 22.22%(10/45),the proportion of SD was 37.8%(17/45),the proportion of PD was 40%(18/35),and the proportion of ORR was 22.2%,The DCR was 60.0% among 56 patients in the immunomonotherapy group(group C),the proportion of PR was 25.0%(14/56),the proportion of SD was 35.7%(20/56),the proportion of PD was 39.3%(22/56),and the proportion of ORR was 25.0%,The DCR was60.7%;Among 36 patients in the combination treatment group(group D),one case was CR(2.80%),PR was 63.9%(23/22),SD was 22.2%(8/36),PD was 11.1%(4/36),ORR was 66.7%,and DCR was 88.9%;2.Comparison of short-term efficacy of each group: the proportion of ORR in the combined treatment groups(group D)was significantly higher than groups B and C,and the ratio among the three groups were66.7% vs.22.2% and 25.0%,P=0.001 < 0.05;The DCR ratio of the combined treatment group was 88.9%,which was statistically significant higher too compared with that of the B and C groups(88.9% vs.60.0%and 60.7%,P=0.0034 < 0.05).3.The survival analysis by Kaplan-Meier method of three groups showed that the m OS in groups A,B,and C,were 8.5 months,10.7months and 10.9 months,respectively.It hasn’t yet been attained in the group D.The m OS among four groups were statistically significant,P =0.001 < 0.05.The m PFS in the groups B and C were 4.6 months and 5.0months,respectively,it hasn’t yet been attained in the group D,and reached the statistical significant among these 4 groups,P = 0.009 < 0.05.4.There was no significant difference in the adverse effects(AE)among the three treatment groups,with all P > 0.05.Reactive capillary hyperplasia was the most common adverse reactions in the combined treatment group and the immunotherapy group alone.The hand and foot reactions were more common in the targeted monotherapy group.Most of the adverse reactions in each group were less than grade III and within the tolerable range.Conclusions:1.Both targeted and immune-monotherapy,and targeted combined immunotherapy have showed a promising efficacy in advanced primary liver cancer.Both single drug therapy and combined immunotherapy can improve the patient’s ORR and DCR significantly,and prolong the OS with mild and controllable AE.2.Compared with the monotherapy regimen,the combination regimen has showed obvious advantages in terms of ORR,DCR,OS and PFS.While achieving the superposition of curative effect,there is no significant difference in the incidence of AE,which can be a better choice for the patients with advanced primary liver cancer.