The Effect Of Antibiotics On The Efficacy Of Immune Checkpoint Inhibitor Treatment In Late-stage Solid Cancer Patients

Part 1:Meta-analysis for the impact of antibiotic administration on the efficacy of immune checkpoint inhibitors in advanced solid tumorsObjective:Immune checkpoint inhibitors(ICIs)have recently achieved inspiring performance in improving the prognosis of various solid tumors.Gut microbiome plays a crucial modulatory role in the efficacy of ICIs,which can be influenced by antibiotic(ATB)administration.In this meta-analysis,we aimed to clarify the correlations of ATB administration with the prognosis of solid cancer patients receiving ICI treatment.Methods:The eligible literatures were searched using PubMed,Cochrane Library,Web of Science,and Clinical trials.gov databases before 29 February 2020.The correlations of ATB administration with overall survival(OS)and progression-free survival(PFS)were determined using Hazard ratios(HRs)coupled with 95%confidence intervals(CIs).Results:A total of 33 studies enrolling 5565 solid cancer patients receiving ICI treatment were included in this meta-analysis.As a whole,ATB administration was significantly correlated worse OS(HR=1.76,95%CI=1.41-2.19,P<0.00001)and PFS(HR=1.76,95%CI=1.472.12,P<0.00001).This significant association was then observed in the subgroup analysis based on region(except for OS in Europe),sample size,age,therapeutic strategy and ICI type.The similar results were also found in subgroup analysis for lung,renal cell(except for OS)and other cancers(such as melanoma)but not for mixed cancers.In addition,the ICI efficacy was more likely to be diminished by ATB administration within a time frame from 60 days before to 60 days after ICI initiation.Conclusion:ATB should be used cautiously in solid cancer patients receiving ICIs.However,further validations are still essential due to existing publication bias.Part 2:The effect of ATBs on the efficacy of immune checkpoint inhibitors in the treatment of advanced solid tumor patientsObjective:To evaluate the effect of antibiotics on the clinical efficacy of immune checkpoint inhibitors(ICI)in the treatment of advanced solid tumor patients.Methods:Clinical data of 136 advanced solid tumor patients treated with ICI from January 2018 to January 2020 in Department of Oncology of our hospital were retrospectively analyzed.The patients were divided into two groups based on receiving ATB within 3 months after ICI therapy or not.Chi-square test was used to analyze the correlation between ATB administration and clinical parameters.Kaplan-Meier analysis was used to analyze the impact of ATB on the overall survival(OS)and progression-free survival(PFS)of patients.Cox proportional hazards regression model was used to identify whether ATB was an independent factor affecting OS or PFS.Results:A total of 136 patients were included,among whom 41 patients were treated with ATB and 95 patients were not treated with ATB.ATB administration was not significantly correlated with gender(x2=0.675,P=0.411),age(χ2=0.403,P=0.526),cancer type(x2=2.647,P=0.266),ECOG score(x2=0.829,P=0.362),and treatment strategy(χ2=0.670,P=0.413).The OS and PFS of the ATB group were significantly lower than those of the non-ATB group(P=0.007,P<0.0002).The multivariate analysis showed that ATB was an independent adverse factor affecting OS(HRF=1.827,95%CI:1.179-2.834,P=0.007)and PFS(HR=1.935,95%CI:1.236-3.029,P=0.004).In subgroup analysis of lung cancer,ATB was significantly correlated with worse OS and PFS(P=0.007,P=0.003).The multivariate analysis also revealed that ATB was also an independent adverse factor affecting OS(HR=3.628,95%CI:1.686-7.808,P=0.001)and PFS(HR=2.663,95%CI:1.323-5.360,P=0.006)in lung cancer.Conclusion:ATB treatment was significantly associated with poor clinical outcomes in advanced solid tumor patients treated with ICIs.Therefore,ATB should be used cautiously in these patients.