Efficacy And Adverse Effects Of Lenvatinib And Immune Checkpoint Inhibitors In Advanced Primary Hepatocellular Carcinoma

Objective:To preliminary comparison and analysis of the efficacy and adverse effects in patients receiving an immune checkpoint inhibitor(PD-1 monoclonal antibody)and the small molecule tyrosine kinase inhibitor lenvatinib for the treatment of advanced primary hepatocellular carcinoma.Methods:The aim of this study was to retrospectively analyse 2021 the clinical data of 129 patients with advanced primary liver cancer admitted to the oncology department of our hospital from 2021 January to 2021 December.All patients were diagnosed pathologically or clinically with a definite stage III or above based on the Chinese staging scheme for liver cancer,and were followed up through the patient case system for previous and recent data,outpatient review and telephone consultation,with a follow-up deadline of December 31,2021.The data collected included: patients’ personal information(gender,ethnicity,age),past history,treatment course,time of initial treatment with study drugs,laboratory parameters(blood tests,urine tests,blood biochemistry),imaging data(computed tomography,MRI,colour Doppler ultrasound),adverse effects during treatment and their severity,and survival status at the end of follow-up.129 Patients were divided into three groups according to the difference in treatment regimen received: lenvatinib treatment group(Group A 35 people),PD-1monoclonal antibody treatment group(Group B 37 people),and combination treatment group(Group C 57 people).The primary endpoint was overall survival(OS,overall survival)and the secondary endpoint was progression-free survival(PFS,progression-free survival).The differences in survival curves between the three groups were compared using the Log-rank method.The data collected on efficacy and safety were collated and the χ2-test was used to analyse the differences in recent efficacy and safety between the three groups,and the recent efficacy was evaluated in terms of CR(complete response),PR(partial remission),SD(stable disease),PD(progressive disease),and disease control.P <0.05 was considered to be a statistically significant difference between groups.Results:1.There was no statistically significant difference between the treatment groups in terms of total bilirubin,albumin and prothrombin time in the 4 weeks before and after treatment in the comparison 3 groups(P> 0.05).2.According to the m RECIST efficacy evaluation criteria: 14.3%(5/35)of PR,40.0%(14/35)of SD,45.7%(16/35)of PD,14.3% of ORR and 54.3% of DCR in the lenvatinib treatment group(Group A).19.0%(7/37)of PR,35.1%(13/37)of SD,45.9%(17/37)of PD,19.0% of ORR and 54.1% of DCR in the PD-1 monoclonal antibody treatment group(Group B).SD accounted for 35.1%(13/37),PD accounted for 45.9%(17/37),ORR ratio was 19.0% and DCR ratio was 54.1%.In the combination therapy group(Group C),the CR rate was 1.8%(1/57),PR rate was 49.1%(28/57),SD rate was 31.6%(18/57),PD rate was 17.5%(10/57),ORR rate was 50.9% and DCR rate was 82.5%.3.The differences in ORR and DCR were compared between the three groups:14.3% ORR and 54.3% DCR in the lenvatinib treatment group(Group A),19.0% ORR and 54.1% DCR in the PD-1 monoclonal antibody treatment group(Group B),and50.9% ORR and 82.5% DCR in the combination treatment group(Group C).The difference in ORR between the three groups was statistically different(c2=17.35,P<0.001),the difference in ORR between the lenvatinib treatment group(group A)and the PD-1 monoclonal antibody treatment group(group B)was not statistically different,and the ORR between the combination treatment group(group C)and the lenvatinib treatment group(group A)and the PD-1 monoclonal antibody treatment group(group B).There was a statistically significant difference in ORR between the combination group(C)and the lenvatinib treatment group(A)and the PD-1 monoclonal antibody treatment group(B)(P < 0.05).There was a statistical difference in DCR between the three groups(c2=11.46,P<0.01),no statistical difference in DCR between the lenvatinib treatment group(Group A)and the PD-1 monoclonal antibody treatment group(Group B),and a statistical difference in DCR between the combination treatment group(Group C)and the lenvatinib treatment group(Group A)and the PD-1monoclonal antibody treatment group(Group B)(P<0.05).4.Kaplan-Meier survival analysis yielded a comparative analysis of survival curves in the three groups: m OS of 10.23 months(95% CI: 9.37,11.09),10.43 months(95% CI: 9.63,11.23)and 12.50 months(95% CI: 12.00,13.00).The difference in m OS between patients in the lenvatinib treatment group(Group A)and the PD-1monoclonal antibody treatment group(Group B)was not statistically significant(P >0.05),and the difference in m OS between patients in the lenvatinib treatment group(Group A)and the PD-1 monoclonal antibody treatment group(Group B)and the combination treatment group(Group C)was statistically significant(P <0.05);the difference in m OS between patients in the lenvatinib treatment group(Group A),the PD-1 monoclonal antibody treatment group(Group B)and the combination treatment group(Group C)had m PFS of 6.96 months(95% CI: 4.93,8.99),7.01 months(95% CI:5.79,8.23),and 9.80 months(95% CI: 6.14,13.46),respectively.The differences in m PFS between patients in the lenvatinib treatment group(Group A)and the PD-1monoclonal antibody treatment group(Group B)were not statistically significant(P >0.05),and the differences in m PFS between the lenvatinib treatment group(Group A)and the PD-1 monoclonal antibody treatment group(Group B)and the combination treatment group(Group B)and the combination treatment group(Group C)were statistically significant(P = 0.031 <0.05).5.When comparing the occurrence of adverse reactions between the three groups according to the type of adverse reactions and the degree of adverse reactions(≤2grade,≥3 grade),only the difference in the occurrence of rash between the PD-1monoclonal antibody treatment group(group B)and the combination treatment group(group C),although not statistically different,was found to be statistically different from the occurrence of rash in the lenvatinib treatment group(group A)(c2=6.84,P=0.03,c2=9.23,P=0.03),while the differences in the occurrence of treatment-related adverse reactions between the remaining groups were not statistically different(P>0.05).There were no deaths due to adverse reactions in any of the three groups,and drug-related adverse reactions were mild and manageable.Conclusion:1.No significant differences in liver function were observed between patients in the lenvatinib treatment group(Group A),PD-1 monoclonal antibody treatment group(Group B)and combination treatment group(Group C)before and after treatment,with manageable adverse effects.2.The combination treatment group(Group C)was significantly better than the lenvatinib treatment group(Group A)and the PD-1 monoclonal antibody treatment group(Group B)in terms of ORR and DCR for the efficacy analysis and m OS and m PFS for the primary and secondary endpoints for the survival analysis.