Clinical Efficacy And Safety Of PD-1 Inhibitor Combined With Chemotherapy In The First-line Treatment Of Advanced Biliary Tract Malignancies

Purpose:To retrospectively investigate the clinical efficacy and safety of PD-1 inhibitor combined with first-line chemotherapy in the treatment of advanced biliary tract malignancies,and to explore possible prognostic factors.Methods:In this study,we retrospectively analyzed patients with advanced biliary tract malignancies from August 2019 to January 2023 in the Department of Oncology,Second Affiliated Hospital of Nanchang University.Clinical data were collected including age,gender,surgical condition,metastatic site,CA19-9 level,treatment protocol,tumor type,ECOG score,absolute value of neutrophils and lymphocytes in peripheral blood within 1 week before treatment.Patients received PD-1 inhibitors in combination with GEMOX(gemcitabine 800mg/m2,iv,d1,d8;Oxaliplatin 85mg/m2,iv,d1,repeated every 2 weeks)or GC(gemcitabine 1000 mg/m2 for 30 min,d1,d8;Cisplatin 25 mg/m2,iv,d1,d8,repeated every 3 weeks),the PD-1 inhibitor is specifically Camrelizumab 200 mg or Sintilimab 200 mg or Tiselizumab 200 mg or pembrolizumab 200 mg.The efficacy was evaluated once every 2 cycles(6 weeks).The efficacy was evaluated according to the RECIST 1.1 efficacy evaluation standard.Treatment-related adverse events were classified and graded according to the adverse reaction terminology version 5.0.The primary endpoints were overall survival(OS)and safety.Secondary endpoints were progression-free survival(PFS),objective response rate(ORR),and disease control rate(DCR).SPSS 26.0 software was used for data analysis.Kaplan-Meier method was used for survival analysis,and OS and PFS survival curves were drawn.The differences among the groups were compared by Log-rank nonparametric test.Cox proportional hazards model was used for univariate and multivariate analysis,and the difference was statistically significant(P < 0.05).Results:1.Survival analysis:The last follow-up was on January 15,2023.The median OS was 12.6 months(95% CI: 11.6-18.0)and the median PFS was 7.7 months(95%CI: 5.0-9.3).Multivariate analysis showed that tumor type was an independent predictor of OS and PFS.2.Efficacy:No patients had a complete response(CR).Eight patients(22.2%)had a partial response(PR),Sixteen(44.4%)patients with stable disease(SD)and 12(33.3%)patients developed disease progression(PD).The objective response rate(ORR)was 22.2% and the disease control rate(DCR)was 66.7%.3.Adverse events:The overall incidence of adverse events during drug use was72.2%.Grade 3 to 4 treatment-related adverse events occurred in 11 patients(30.6%),primarily including 5 patients(13.9%)with thrombocytopenia,3(8.3%)white blood cell decreases and 3(8.3%)neutropenia.Grade 4 treatment-related adverse events-white blood cell and thrombocytopenia in two patients.The main immunotherapy-related adverse events were hypothyroidism of the thyroid gland(n=8,22.2%),reactive cutaneous capillary endothelial proliferation(n=6,16.7%),pruritus(n=3,8.3%)and rash(n=3,8.3%).No fatal treatment-related adverse reactions occurred.Conclusions:The combination of PD-1 inhibitor and chemotherapy in the first-line treatment of advanced biliary malignancies shows better efficacy,controllable safety and well tolerated.