Efficacy Evaluation Of Nilotinib Treatment In Different Genomic Subtypes Of Gastrointestinal Stromal Tumors: A Meta-analysis

Objective: Gastrointestinal stromal tumor is the most common mesenchymal tumor of the digestive tract,has the potential of malignant transformation.They are usually positive in the expression of CD117(c-kit),mainly caused by the activation of mutations in Kit or PDGFRA.Currently,targeted drugs are used as the routine treatment for gastrointestinal stromal tumors,and the efficacy is remarkable.Nilotinib has been used as a third-line treatment for gastrointestinal stromal tumors following the failure of imatinib and sunitinib.Previous studies have shown that there are significant biological differences among the gene subtypes of gastrointestinal stromal tumors,and there are significant differences between imatinib and sunitinib in the treatment of gastrointestinal stromal tumors with different genotypes.In this study,we aimed to evaluate the efficacy of nilotinib in different genomic subtypes of GIST.Methods: We searched the English articles through EMBASE,Cochrane Library and Pub Med Database regarding to the use of nilotinib on GISTs,which published up to Aug 15,2019.Limit the study to a randomized controlled clinical trial,then the quality of all retrieved articles was screened and evaluated.Inclusion criteria were: GISTs patients received nilotinib in a clinical trial and had detailed genetic subtype records(such as KIT exon 9,KIT exon 11,or PDGFRA mutations,or wild-type).The clinical benefit rate(CBR)was used to assess the efficacy of nilotinib.Outcomes subjected to analysis was CBR.Statistical analyses were performed using STATA version 14.0.Weighted Odds ratio(OR)with 95% confidence intervals(CIs)were calculated for the outcomes.Fixed-effects or random-effects models were used,depending on the degree of heterogeneity across the selected studies.Results: Our meta-analysis included a total of three studies,with 372 patients participating in these clinical trials,but some patients who did not meet the clinical trial criteria were excluded.Finally,222 cases of gastrointestinal stromal tumor were included in this meta-analysis.There were few cases with mutations in PDGFRA,so data for PDGFRA genotypes was not statistically analyzed.The overall OR(KIT group vs WT group)was 3.26(95% CI: 1.14–9.28;P = 0.027,Pheterogeneity = 0.613).The overall OR in KIT exon 11 group vs WT group was 5.30(95% CI: 1.79–15.68;P = 0.003,Pheterogeneity = 0.409).The overall OR in KIT exon 9 group vs WT group was 0.13(95% CI: 0.02–0.86;P = 0.035,Pheterogeneity = 0.229).The overall OR in KIT exon 11 group vs exon 9 group was 9.96(95% CI: 0.39–254.66;P <0.0001,Pheterogeneity = 0.024).Conclusions: The response of gastrointestinal stromal tumors with different gene subtypes to nilotinib is different.Among them,gastrointestinal stromal tumors with KIT exon 11 mutation can benefit the most from the treatment of nilotinib,followed by KIT exon 9 mutation and wild-type gastrointestinal stromal tumors.In addition,gastrointestinal stromal tumor patients may develop secondary gene mutations after targeted drug therapy,and the type of secondary gene mutations may affect the efficacy of nilotinib.