Efficacy Of Bevacizumab Combined With Chemotherapy As First-line And Second-line Treatment In Metastatic Colorectal Cancer

Objective:Chemotherapy-based comprehensive therapy is the main treatment strategy for patients with metastatic colorectal cancer,while the prognosis of these patients has been improved by the use of targeted therapies.The recombinant humanized monoclonal antibody bevacizumab can selectively bind to human vascular endothelial growth factor(VEGF)and block its biological activity,and has been widely used in the treatment of mCRC in combination with chemotherapy.Bevacizumab has been on the market for 9 years,but there is insufficient data on real-world clinical practice.This study was designed to analyze the efficacy of bevacizumab combined with chemotherapy as first-line and second-line treatment in metastatic colorectal cancer.Methods:Retrospectively collected 130 patients with metastatic colorectal cancer,who had been treated in the Cancer Hospital Chinese Academy of Medical Sciences from January 1,2011,to February 28,2017.The deadline for follow-up is February 28,2019.All patients received at least two chemotherapies,and bevacizumab was combined with first-line or(and)second-line chemotherapy.Compare the efficacy of bevacizumab in combination with chemotherapy and chemotherapy alone.Based on the use of bevacizumab,the patients were divided into three groups and the efficacy of these groups was statistically compared:first-line group(bevacizumab only combined with first-line chemotherapy),second-line group(bevacizumab only combined with second-line chemotherapy),and cross-line group(bevacizumab combined with both first-line and second-line chemotherapy).Multivariate analyses were performed on factors that may affect the efficacy.The primary endpoints were overall survival(OS)and progression-free survival(PFS).PFS1 was defined as PFS of the first-line treatment,PFS2 was defined as PFS of the second-line treatment,and cumulative PFS was defined as PFS1+PFS2.OS was the time from the start of first line treatment to death for any reason.Results:The median age of the 130 patients enrolled in the study was 54 years(28-75 years),of which 52.3%were men,97.7%of patients had an ECOG score of?1.There were 64 patients treated with bevacizumab in first-line treatment,of which 47 patients used bevacizumab in the second-line treatment continuously,17 patients without bevacizumab in the second-line treatment(12 patients with chemotherapy alone,5 patients with anti-EGFR therapy).There were 113 patients treated with bevacizumab in second-line treatment,,including 66 patients who were not treated with bevacizumab in the first-line treatment(58 patients with chemotherapy alone,8 patients with anti-EGFR therapy),and 47 patients who were treated with bevacizumab in the first-line treatment.The median OS of the whole group was 31.50(95%Cl 28.38-34.62)months.In the first-line treatment,the mPFS1 of chemotherapy combined with bevacizumab and chemotherapy alone were 7.73months and 5.80 months respectively,with statistical difference(P<0.001).In the second-line treatment,the mPFS2 of chemotherapy combined with bevacizumab and chemotherapy alone were 5.27 months and 2.03 months respectively,with statistical difference(P<0.001).Among the patients received second-line chemotherapy combined with bevacizumab,subgroup analysis was performed based on whether bevacizumab had been used in first-line treatment.As a result,the mPFS2 of the two subgroups were 5.13 months and 5.60 months respectively,and the difference had no statistically significant(P=0.694).The median cumulative PFS of the first-line group,the second-line group and the cross-line group were 11.2months,12.07 months and 12.73 months respectively,with no statistical difference(P=0.22).The mOS were 18.87 months,32.97 months and 27.83 months respectively,with no statistical difference(P=0.284).After the data corrected(excluded the patients who used anti-EGFR treatment in the first-line and second-line treatment),the median cumulative PFS of the first-line group,the second-line group and the cross-line group were 9.97months,11.97 months and 12.73 months respectively,still with no statistical difference(P=0.083).The mOS were 14.93 months,32.17 months and 27.83 months respectively,with statistical difference(P=0.03).The mOS of the second-line group and the cross-line group were better than the first-line group,and there was no significant difference in mOS between the second-line group and the cross-line group.Conclusion:Real-world results show that the efficacy of bevacizumab in combination with chemotherapy is consistent with the results reported in clinical trials.the cumulative PFS and OS of second-line or cross-line groups have a prolonged trend compared with first-line group.The effect of anti-EGFR monoclonal antibody on the efficacy of bevacizumab remains to be further studied.