| Objective: To retrospectively analyze the efficacy,influencing factors and safety of three inhibitors of programmed cell death-1(PD-1),Camrelizumab,Tislelizumab and Sintilimab,in the second-line treatment of advanced esophageal squamous cell carcinoma.Methods: The clinical data of 99 patients with advanced esophageal squamous cell carcinoma who received second-line treatment with PD-1 inhibitor in Subei People’s Hospital of Jiangsu Province from January 2020 to December 2022 were analyzed retrospectively.According to the actual treatment methods,the patients were divided into single immunization group(n=26)and combined immunization group(n=73).In the combined immunization group,based on the specific clinical implementation plan,they were divided into immunization combined chemotherapy group(n=63)and immunization combined anti-vascular group(n=10);in terms of the types of immune drugs actually received,patients were divided into Camrelizumab group(n=56),Tislelizumab group(n=12)and Sintilimab group(n=31).According to the patients need to use antibiotics and glucocorticoids in the course of clinical treatment,the study aims to explore the relationship between antibiotics and glucocorticoids and the efficacy of immunotherapy.The efficacy and safety were evaluated according to modified RECIST1.1 for immune based therapeutics i RECIST and the National Cancer Institute General Toxicity Criteria(NCI-CTC 5.0).The primary study endpoints included overall survival(OS)and Pprogression-free survival(PFS),while the secondary study endpoints included objective response rate(ORR),disease control rate(DCR)and the incidence of treatment-related adverse events(TRAEs).The survival curve was drawn by Kaplan-Meier method,and the prognostic factors were analyzed by Cox proportional risk regression model.The difference was statistically significant when P < 0.05.Result: 1.Analysis on the curative effect of the whole group of patients: follow-up through December 1,2022,The median overall survival time and median progression-free survival time for the primary study endpoint were 17.4 months and7.43 months,respectively,and ORR and DCR for the secondary study endpoints were22.2%and 91.9%,respectively.2.Analysis on the curative effect of different treatment regimens:(1)Comparison between the single-drug immunization group and the combined immunization group:The median OS of the two groups were 9.83 months and 19.63 months respectively(P=0.018),and the median OS of the combined immunization group was significantly longer,with significant difference;The median PFS of the two groups were 4.33 months and 8.23 months respectively(P=0.11),with no statistical difference;The ORR of the two groups were 19.2% and 23.3%(P=0.879),and the DCR of the two groups were88.5% and 93.2%(P=0.738),respectively,with no statistical difference between the two groups.(2)Comparison between the immunization combined chemotherapy group and immunization combined anti-vascular group: The median OS was 19.63 months and18.9 months(P=0.55),the median PFS was 9.87 months and 7.43 months(P=0.67),the ORR was 30%,22.2%(P=0.890),the DCR was 90.0%,93.7%(P=1.000),respectively,with no statistical difference in median OS,median PFS,ORR and DCR between the two groups.(3)Comparison among the three immunological drugs: The median OS of Camrelizumab group,Tislelizumab group and Sintilimab group were 10.97 months,19.57 months and less than(P=0.31);The median PFS were 7.13 months,4.43 months and 9.27 months,respectively(P=0.81);The ORR were 17.9%,16.7% and 32.3%(P=0.267),and the DCR were 92.9%,91.7% and 90.3%(P=0.917),respectively,with no statistical difference in median OS,median PFS,ORR and DCR between the three groups.3.Analysis on prognostic factors:(1)The median OS and median PFS of the patients treated with PD-1 inhibitors within 60 days were significantly lower than those without antibiotics(P=0.031,P=0.045);(2)The median OS and PFS of patients treated with glucocorticoid(equivalent dose of prednisone ≥ 10mg/d)within 30 days before and after PD-1 inhibitor treatment were lower than those without glucocorticoid(equivalent dose of prednisone < 10mg/d),without statistical difference(P=0.063,P=0.17).(3)Univariate and multivariate analysis showed that antibiotic use,ECOG score,radiotherapy history and treatment mode were independent prognostic factors of OS in patients with advanced esophageal squamous cell carcinoma,antibiotic use and ECOG score were that of PFS.4.Security analysis: 85 patients(82.86%)had treatment-related adverse events,Immune-related adverse events(immue-related adverse events,ir AEs)occurred in 42patients(42.4%),and 4 patients(4.0%)had grade 3-4 ir AEs,including 2 cases of reactive cutaneous capillary endothelial proliferation(RCCEP)and 2 cases of immune pneumonia.After stopping immunotherapy and giving glucocorticoid treatment,there was no grade 5 treatment-related adverse events,treatment-related deaths and unexpected adverse events.Conclusion: 1.Retrospective analysis indicates that PD-1 inhibitor can prolong the median OS and median PFS of patients with advanced esophageal squamous cell carcinoma in the real-world study of second-line treatment,with controllable safety;Combined therapy can prolong the survival of patients compared with single drug therapy.The three PD-1 inhibitors,Camrelizumab,Tislelizumab and Sintilimab,have similar clinical benefits in the second-line treatment of advanced esophageal squamous cell carcinoma.2.Antibiotic use is associated with reduced efficacy in immunotherapy patients with advanced esophageal squamous carcinoma.Antibiotic use is an independent adverse prognostic factor affecting patients’ OS and PFS,and clinical caution is required during PD-1 inhibitor therapy.3.Glucocorticoid use did not reach a statistical difference in the decrease of OS and PFS in patients with immunotherapy advanced esophageal squamous carcinoma,but glucocorticoid use reduced the absolute values of median OS and median PFS in patients. |
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