Efficacy And Safety Analysis Of Immune Checkpoint Inhibitors Combined With Chemotherapy And Chemotherapy Alone In Second-line Treatment Of Patients With Advanced Biliary Malignancy

Background and Purpose:Biliary tract carcinoma(BTC)is a heterogeneous malignant disease occurring in the biliary tract tree,with poor prognosis,short survival and poor second-line treatment.The Immune checkpoint inhibitors(ICIs)have achieved satisfactory efficacy in the treatment of a variety of cancers,but are still in the exploratory stage in the treatment of advanced biliary tract carcinoma.Therefore,we through the study compared the immune checkpoint inhibitors(ICIs)combination chemotherapy with simple chemotherapy for the treatment of late BTC second-line treatment efficacy and safety,further demonstrates the immune therapy in the second-line treatment of advanced BTC feasibility.At the same time,the potential biomarkers for predicting response were explored to provide a new idea for second-line treatment of advanced BTC.Method:In this study,32 patients with advanced biliary malignancy who were diagnosed in the Second Affiliated Hospital of Nanchang University and met the inclusion criteria from October 2015 to October 2020 were included in the retrospective analysis.The patients were divided into chemotherapy group and combined group,16 cases in each group.The chemotherapy group was treated with chemotherapy alone,while the combined group was treated with ICIS combined with chemotherapy.Response Evaluation Criteria for Solid Tumor(RECIST)Version 1.1was used to evaluate the efficacy of the treatment.Objective response rate(CR+PR),disease control rate(CR+PR+SD),median progression-free survival(m PFS)and median survival(m OS)of the two groups were observed.Next Generation Sequencing(NGS)was used for Sequencing related genes of tumor tissue samples of11 patients,and the correlation between clinical and genomic characteristics and clinical outcomes was evaluated.At the same time,the incidence of adverse reactions in the two groups was statistically analyzed to evaluate the safety of ICIS combined with chemotherapy in the treatment of advanced BTC.Results:This study included 32 patients with advanced BTC.And the follow-up date was February 28,2021.Data showed 19 cases of intrahepatic cholangiocarcinoma.9cases of hilar cholangiocarcinoma.1 case of distal cholangiocarcinoma.3 cases of gallbladder carcinoma.The results show that: The total number of complete remission(CR)and partial remission(PR)patients in the chemotherapy group was 0,and the number of stable disease(SD)patients was 62.5%.Progressive of disease(PD)was observed in 6 patients(20%).In the combined group,CR was 0,PR was 3(18.75%),SD was 13(81.25%),and PD was 0.The objective response rate(ORR)and disease control rate(DCR)of the chemotherapy group were 0 and 62.5%.The ORR and DCR of the combined group were 18.75% and 100.00% respectively.The m PFS of the chemotherapy group was 4.4 months,and the m PFS of the combined group was 7.6 months,and the m PFS of the combined group was 4.25 months,and the m PFS of the combined group was 8.733 months.There were no statistically significant differences in m PFS(p=0.2022)and m OS(p=0.3797)between the two groups.Genetic survival analysis was performed using Kaplan-Meier curves to assess the impact of gene mutations on PFS.Patients with STK11,FRS2,ERCC2 and MDM2 mutations had significantly shorter PFS compared with wild-type patients.The main adverse reactions in the chemotherapy group were myelosuppression,fatigue and fever etc.While in the combined group,the main adverse reactions were fatigue,rash,hypothyroidism and myelosuppression.No grade 4 or above adverse reactions were found in the two groups.Multivariate analysis showed that surgical resection,interventional therapy can improve survival in patients with advanced BTC.Conclusion:Second-line treatment with ICIs combined with chemotherapy in BTC patients did not extend m PFS and m OS in patients compared to chemotherapy alone,but patients who responded to ICIs treatment extended their survival.Combination therapy improved patients’ ORR and DCR.Univariate analysis showed that mutations in STK11,FRS2,ERCC2,and MDM2 shortened PFS in patients.Combined treatment with ICIS did not increase adverse events in patients,and ICIS is safe and tolerable in patients with advanced BTC.