Efficacy And Safety Of Bevacizumab With Chemotherapy In Different Intervals As First Line Treatment For Metastatic Colorectal Cancer: A Comparative Real-word Study

Objective:Bevacizumab combined with chemotherapy is the standard first-line treatment regimen for metastatic colorectal cancer,of which the three-week regimen is widely used in clinical practice,but many patients have not been given the scheduled treatment due to economic difficulties,severe toxicity and other reasons.There are cases of extending the dosing interval(four-week regimen).The purpose of this study was to compare the efficacy and safety of patients with extended treatment intervals(fourweek regimen)in the real world compared with those with regular dosing(three-week regimen),and to analyze the factors affecting the prognosis of patients with metastatic colorectal cancer.Comparing the quality of life of the two groups of patients and exploring the impact of extended dosing intervals(1 week)on patients in the real world.Methods:Patients with metastatic colorectal cancer who were treated with bevacizumab in addition to first-line standard chemotherapy in our hospital from August 1,2017 to October 1,2020 were retrospectively collected.Follow-up ended on October 1,2021,with a median follow-up period of 33.4 months.Subjects were screened according to inclusion criteria and exclusion criteria,and the interval time of first-line bevacizumab combined with chemotherapy in the 6 treatment cycles was calculated.Patients were divided into standard interval(three-week regimen)group and extended interval(fourweek regimen)group according to the interval time of administration.Data were collected through medical records and telephone follow-up,and analyzed by SPSS20.0to compare the efficacy and incidence of adverse reactions between the two groups,explore prognostic factors and progressive subgroup analysis,and evaluate the quality of life of patients in the two groups.Results:1.A total of 91 eligible cases were included,including 47 patients in the first-line bevacizumab combined with chemotherapy in metastatic colorectal cancer group with standard interval(three-week regimen)and 44 in extended interval(four-week regimen)group.The baseline clinical characteristics were similar.2.Objective response rate(P=0.761)and disease control rate(P=1.000)were similar between first-line bevacizumab plus chemotherapy with standard interval(three-week regimen)and extended interval(four-week regimen)in metastatic colorectal cancer,the difference was not statistically significant,and there was no significant difference in the short-term efficacy between the two groups.3.The median PFS of first-line bevacizumab combined with chemotherapy with standard interval(three-week regimen)group versus extended interval(four-week regimen)group of metastatic colorectal cancer was(9.13 vs 9.90 months,P=0.594),The median OS was(19.60 vs 24.87 months,P=0.180),the difference was not statistically significant,and there was no significant difference in the long-term efficacy between the two groups.4.The incidence of adverse reactions was similar in the standard interval(threeweek regimen)and extended interval(four-week regimen)groups of first-line bevacizumab combined with chemotherapy for metastatic colorectal cancer(P>0.05),with the highest incidence of neutropenia,which was more than 80% in both groups,and the incidence of grade 3-4 was nearly 20%.5.Univariate analysis showed that the OS of patients with primary tumor resection was longer than that of non-resection patients(P=0.010),and the OS of patients with metastases to one organ was longer than that of patients with metastases to multiple organs(P=0.004).Further multivariate analysis showed that resection of the primary tumor and the number of metastatic organs were independent prognostic factors for OS.6.Subgroup analysis showed that patients’ age,gender,creatinine clearance rate,primary tumor resection,number of metastatic organs,primary tumor site,CEA level,basis of first-line chemotherapy versus first-line bevacizumab combined with chemotherapy for metastatic colorectal cancer There was no significant difference in PFS and OS between the standard interval(three-week program)group and the extended interval(four-week program)group,P>0.05.7.After 6 cycles of treatment,the score of physical function in the first-line bevacizumab combined with chemotherapy extended interval(four-week regimen)group was higher than that in the standard interval(three-week regimen)group,and the difference was statistically significant(P=0.016),while there was no statistical difference in the scores of other indicators.Further analysis of individual changes in all item scores before and after 6 cycles of treatment showed that,although there was no statistically significant difference between the two groups,significantly more patients in the extended interval(four-week regimen)improved and/or less patients deteriorated than in the standard interval(four-week regimen)group.Conclusion:In real-world clinical practice,for patients with severe adverse reactions,appropriately extending the treatment interval(1 week)of first-line bevacizumab combined with chemotherapy for metastatic colorectal cancer has no significant effect on the efficacy of patients,and is conducive to improving patients’ quality of life.