An Assessment Of Camrelizumab Combined With Chemotherapy In Metastatic Biliary Tract Cancers

Purpose:Monoclonal antibodies that target the PD-1 receptor are emerging as promising therapeutic candidates for the treatment of biliary tract cancers(BTCs).The purpose of the current study was to assess the combination of the Camrelizumab with chemotherapy as a first-line treatment for metastatic BTCs.Method:We conducted a prospective single-arm observational pilot study from July 2018 to December 2019.A total of 14 patients with a ECOG score of 0-1 who hadn’t received any chemotherapy,radiotherapy,immunotherapy were enrolled in this study.All patients received Camrelizumab immunotherapy combined with different chemotherapy regimens.Camrelizumab was given intravenously 3mg/kg every 2weeks or every 3 weeks on day 1 of chemotherapy regimens.Regimens included FOLFOX-4(oxaliplatin 85 mg/m2 IV on day 1;levoleucovorin calcium 200 mg/m2 over 2 h on day 1;fluorourea 400 mg/m2 IV on day 1 followed by 600mg/m2 civ over 22 h for 2 days,every 2 weeks),GEMOX(Gemcitabine 800 mg/m2 IV on day1;oxaliplatin 85 mg/m2 IV on day 1,every 2 weeks),TS(paclitaxel liposome 175mg/m2 IV on day 1,S-1 60 mg twice daily PO for 14 days,every 3 weeks)or S-1monotherapy(60 mg twice daily PO for 14 days,every 3 weeks).Tumor response was determined through radiological review and judged according to RECIST guidelines.All toxicities or adverse effects were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events(v4.0).The primary efficacy endpoints were objective response rate(ORR),disease control rate(DCR),progression free survival(PFS),and overall survival(OS).The Kaplan-Meier method was used to estimate survival analysis,and Cox proportional hazard model was used for multivariate analysis.P?<?0.05 was considered statistically significant.Result:1.Efficacy: At data cutoff,No patient achieved CR,two(14.29%)exhibited PR,seven(50%)had SD,and five(35.71%)experienced PD.The objective response rate(CR+PR)and disease control rate(CR+PR+SD)were 14.3% and64.3% respectively.2.Survival analysis: The median PFS was 6.5 months(95% CI: 3.8-9.2),and the median OS was 9.9 months(95% CI: 7.6 to 12.2).The 6-and 12-month PFS rates were 61.6% and 12.3%,respectively,whereas the 6-and 12-months OS rates were74.5% and 26.6%,respectively.Patients with single metastases and those who received >4 cycles of combination treatment tended to have longer median PFS(P=0.026 and P=0.006,respectively)and OS(P=0.007 and P=0.002,respectively).3.Adverse events: Treatment-related adverse events(TRAEs)occurred in all patients.The most frequent TRAE was vomiting(n=7,50%),followed by fever(n=6,42.86%),nausea(n=5,5.71%),fatigue(n=4,28.57%).Grade 3/4 TRAEs occurred in 6(42.86%)patients.These included 4(28.6%)vomiting episodes,3(21.4%)neutropenic episodes.Camrelizumab-related AEs of any grade occurred in5(35.71%)patients,including 2(14.3%)hemangiomas and 2(14.3%)episodes of colitis,and single(7.1%)episodes of hypothyroidism and hepatitis.All symptoms responded to supportive care.No drug-related deaths occurred.Conclusion:Camrelizumab combined with chemotherapy as first-line treatment for metastatic BTCs demonstrated acceptable safety and efficacy in our pilot study.