The Efficacy Of First-line Chemotherapy Regimens Combined With Bevacizumab And The Relationship Between The Efficacy And The Status Of RAS And BRAF Genes In Metastatic Colorectal Cancer

ObjectiveTo investigate the efficacy of bevacizumab combined with different first-line chemotherapy regimentsfor advanced colorectal cancer(mCRC),and the correlation between efficacy and KRAS and BRAF gene status,primary tumor site,and different treatment conditions.Methods216 mCRC patients who had received KRAS gene and BRAF gene test and met the inclusion conditions were selected and given first-line chemotherapy(FOLFOX/XELOX or FOLFIRI/XELIRI)combined with bevacizumab according to the self-selected regimen of physicians.4～8 cycles of chemotherapy(3-6 months)were planned for induction therapy.Evaluate every 2 cycles.According to the evaluation criteria of solid tumor efficacy(RECIST 1.0),the correlation between KRAS gene and BRAF gene status and the objective remission rate(ORR),median progression-free survival(mPFS)and median total survival(mOS)of first-line chemotherapy combined with bevacizumab was retrospectively analyzed.Adverse reactions to treatment were evaluated.Results1.KRAS mutation rate was 36.6%and BRAF mutation rate was 6.5%.In the BRAF wild-type group,compared with KRAS wild-type patients,the incidence of low-differentiated adenocarcinoma in KRAS mutant patients was higher(51.3%vs.30.6%,P=0.003),and the number of intrahepatic lesions>3(59.0%vs.39.5%,P=0.023),with statistically significant differences(P<0.05).In KRAS wild-type group,compared with the mutated BRAF gene in patients with wild type,mutated BRAF gene mutation type patients with poorly differentiated adenocarcinoma of the probability is higher(61.5%vs.30.6%,P=0.011)and more likely to have transferred to the liver(84.6%vs.64.5%,P=0.049)and intrahepatic lesion number 3 or higher(72.7%vs.39.5%,P=0.004)and peritoneal(84.6%vs.29.0%,P=0.000),the difference had statistical significance(P<0.05).BRAF wild-type patients had higher mOS than mutant patients(18.1m vs.14.9m,P=0.026),and the difference was statistically significant(P<0.05).2.The ORR between the patients with KRAS gene mutation and those with KRAS wild-type showed no significant difference(P>0.05).There were no statistically significant differences in ORR,mPFS and mOS between the three groups receiving FOLFOX,XELOX and FOLFIRI combined with bevacizumab(P>0.05).There was no significant difference in ORR between patients with BRAF gene mutation and those with BRAF gene wild-type(P>0.05).Among the treatment regimens of the three groups,there was no statistically significant difference in ORR and mPFS(P>0.05),while the mOS of patients with BRAF gene mutation was lower than that of wild-type patients,as FOLFOX+Bev(14.6m vs.17.6m,P=0.043),XELOX+Bev(15.1m vs.17.9m,P=0.036),FOLFIRI+Bev(14.9m vs.17.1m,P=0.038),respectively.There were statistically significant differences(P<0.05).3.In the patients with wild-type KRAS and wild-type BRAF genes,the ORR between previous exposure and primary exposure were 30.2%vs.51.4%(P=0.032),the mPFS were 8.3months vs.9.5months(P=0.043),respectively.There were statistically significant differences in ORR and mPFS between the two groups(P<0.05).For patients with KRAS gene and patients with BRAF gene mutation,there was no significant difference in ORR and mPFS between previous exposure and initial exposure(P>0.05).4.There were no statistically significant differences in ORR and mPFS between KRAS gene mutant and KRAS gene wild-type patients for mCRC patients with different tumor primary sites(left and right hemicolon)(P>0.05).There was no significant difference in ORR and mPFS between the patients with BRAF gene mutation and those with BRAF gene wild-type(P>0.05).5.Multi variate Cox regression analysis showed that KRAS gene mutation could not be used as mOS(hazard ratio=0.533;95%CI:0.238 to 1.352;P=0.183),(P>0.05);BRAF gene mutation can be used as mOS(hazard ratio=0.336;95%CI:0.135 to 1.693;P=0.036),(P<0.05).Conclusions1.The ORR between the mutation group and wild group of KRAS gene and BRAF gene were not significant difference in mCRC received a first-line chemotherapy regimen(FOLFOX/XELOX,FOLFIRI)combined with bevacizumab;the mOS of patients with BRAF gene mutation was significantly lower than that of the wild type;2.For the wild type of KRAS gene and BRAF gene,the efficacy(ORR/mPFS)of patients with primary exposure is better than that of previous exposure;3.There was no statistical difference in the prognosis of mCRC in different primary sites(left and right colon);4.BRAF gene mutation status can predict mOS,and itself is a poor prognostic factor.