Efficacy And Safety Of Anti-PD-1 Immunotherapy For Advanced Hepatocellular Carcinoma

Objective : Liver cancer is a malignant tumor with high incidence and mortality worldwide.The emergence of immunotherapy has brought a milestone change in the systemic treatment on liver cancer.A retrospective study was conducted to analyze the efficacy and safety of patients with advanced hepatocellular carcinoma who received PD-1 antibody monotherapy or combination therapy with anti-angiogenic drugs in Department of Oncology,the First Affiliated Hospital of Anhui Medical University.This study provide reference for application of PD-1 antibodies and combination therapy in clinical work.Methods : Collect clinical and survival data of patients with advanced HCC who received PD-1 antibody monotherapy or combination therapy in our hospital from2017-06-01 to 2020-11-30.Patients were assigned according to monotherapy or combination therapy,with or without lung metastases,first-or second-line treatment to analyze efficacy and safety of treatment.The efficacy data was based on the best response,including overall response rate(ORR)and disease control rate(DCR),chi-square test was used to compare differences between groups.The Kaplan-Meier method was used to estimate the median progression-free survival(m PFS)and median overall survival(m OS)of each group.We used Log rank test to compare the difference between groups.Results:A total of 73 patients with advanced HCC were enrolled in the study.The median age of all patients was 56 years old,34 patients received monotherapy(47%),39 pts(53%)combined therapy;42 pts(58%)with lung metastases,31 pts without lung metastases(42%);52 pts(71%)were treated as first-line treatment,21 pts(29%)were treated as second-line treatment.The ORR and DCR of all 73 patients were 31%(23/73)and 74%(54/73),respectively;m PFS and m OS were 6.73(95% CI,0.00-15.10)months and NR(not reached),respectively.ORR(32% [11/34] vs 31%[12/39],p=0.82)and DCR(76%[26/34] vs 72%[28/39],p=0.65)in monotherapy and combination therapy had no significant differences.The m PFS and m OS of the combination group were 9.57(3.94-15.20)months and NR,respectively,which were both longer,compared with the m PFS(4.53 [0.00-13.65])months and m OS(12.43 [0.00-27.01])months of monotherapy.The difference in m OS between the two was statistically significant(p=0.047).The ORR of pts with or without lung metastases were 38% and 22%(p=0.16),and the DCR were 74% and 74%(p=0.97),respectively.The median PFS in the pts with lung metastases was 12.37(0.10-24.63)months,and the median OS had not been reached,compared with pts without metastases(median PFS: 3.9[2.50-5.30]months;median OS: 9.83 [7.76-11.90]months)were longer,but the difference was not statistically significant(median PFS: p=0.09;median OS: p=0.27).The median control duration of pulmonary lesions was significantly longer than that of extrapulmonary lesions(NR vs 12.37 [95% CI,0.00-24.85] months,p = 0.048).We also analyzed the efficacy of first-line and second-line treatment.The ORR of the two groups were 27%(14/52)and 43%(9/21)respectively,which had no statistically significant difference(p=0.19).The PFS were 16.33(1.16-31.50)months and 6.73(0.00-15.76)months(p=0.95),and the median OS were 27.17(0.00-41.10)months and20.23(5.07-35.40)months(p=0.15).The incidence of adverse reactions in all patients was 77%(56/73).The most common treatment-related adverse events in all patients were elevated alanine aminotransferase or aspartate aminotransferase(ALT/AST)[23(32%)],reactive cutaneous capillary endothelial proliferation(RCCEP)[20(27%)]and increased bilirubin [16(14%)].There was no significant difference in the incidence of adverse events in all groups(monotherapy vs combination: 76% vs 77%,p=0.96;with vs without lung metastases: 67% vs 62%,p = 0.69;first-vs second-line treatment:77% vs 76%,p=0.95)Conclusion:PD-1 antibody monotherapy and anti-PD-1 immunotherapy combined with anti-angiogenic treatment had good efficacy and controllable safety in the first-line and second-line treatment of advanced hepatocellular carcinoma.The efficacy of the combined therapy is better than that of monotherapy.Pulmonary metastases of HCC had better therapeutic effects on PD-1 antibody than expulmonary metastases,and the mechanisms need to be further explored.