Effects Of Antibiotics On The Efficacy Of Bevacizumab-based Treatment In Metastatic Colorectal Cancer

Objective:This study retrospectively analyzed the effect of antibiotics on the efficacy of bevacizumab in the treatment of metastatic colorectal cancer.Methods:92 pathologically proved m CRC patients administered between January 1,2011 and October 1,2017 who received Bevacizumab monoclonal antibody therapy,with complete records of treatment outcomes and survival data,were studied.The survival analysis was performed according to factors such as age,gender,body mass index(BMI),ECOG performance status,K-ras status,cell grade,tumor location,number of metastatic organs,surgery history of the primary cancer,and antibiotic exposure.To evaluate the efficacy of first-line and second-line bevacizumab combined with chemotherapy in patients with metastatic colorectal cancer,and to correlate the patient's objective efficacy,disease control rate,progression-free survival time with the use of antibiotics.Assessing criteria of treatment outcomes were based on the Response Evaluation Criteria in Solid Tumors(RECIST)1.1 version.Objective response rate(ORR)% was calculated as the proportion of patients with Complete response(CR)and Partial response(PR).Disease control rate(DCR)% was defined as the proportion of patients with Complete response(CR),Partial response(PR)and Stable disease(SD).Statistical analysis was performed by SPSS 23.0.Results:1.Cox survival analysis was used to determine the prognostic factors of bevacizumab-based treatment in colorectal cancer.Univariate Log-rank analysis suggested that ECOG performance status,BMI,surgery history of the primary cancer and antibiotic exposure were identified to be correlated with OS.In multivariate Cox regression,antibiotic exposure was proved to be a significant independent prognostic factor for poor OS in m CRC patients(HR=2.32,95% CI1.24-4.36,P=0.009).The other independent prognostic factor was ECOG performance status(P=0.040),BMI(P=0.025).2.The median progression-free survival(m PFS)was 11.6 months in all patients receiving bevacizumab first-line therapy,and the median overall survival(m OS)was 23 months..There were 31 used antibiotics and 38 without antibiotics.In the antibiotics(+)group and antibiotics(-)group,the ORR was 32.3% compared with 23.7%(P=0.428),and the DCR was 80.6% compared with 86.8.%(P=0.712).There was no statistical significance in the ORR and DCR between the two groups.The m PFS of the two groups was 8.6 months and 17.8 months(P=0.010),and the m OS was 13.8 months to 33.5 months,both have statistical significant.3.The median progression-free survival(m PFS)was 13.4 months in all patients receiving bevacizumab second-line therapy,and the median overall survival(m OS)was 25.6 months.There were 18 used antibiotics and 23 without antibiotics.In the antibiotics(+)group and antibiotics(-)group,the ORR was 11.1% compared with 8.7%(P=1.000),and the DCR was 72.2% compared with 78.3%(P=0.936).There was no statistical significant in the ORR and DCR between the two groups.The m PFS of the two groups was 8.7 months to 15.3 months(P=0.036),and the m OS was 19.3 months to 32.1 months,both have statistical significant.Conclusions:The use of antibiotics shorten the PFS and OS in the first and second line with Bevacizumab-based treatment m CRC.The possible mechanism is antibiotics affect the immune system by affecting the intestinal flora,thereby affecting the efficacy of Bevacizumab,suggesting that the immune system and the composition of the intestinal microbiota may serve as a predictor of the efficacy of bevacizumab in the treatment of m CR.This efficacy prediction indicators need to be confirmed by studies.