Relationship Between Efficacy Of Sunitinib And C-kit Mutation Of Patients With Advanced Gastrointestinal Stromal Tumors After Failure Of Imatinib:A Systematic Review

Objective:A large number of studies have shown that c-kit mutations are closely related to the prognosis of gastrointestinal stromal tumors(GISTs).At the same time,Sunitinib(SU)has become the second-line recommended drug for GISTs because of its efficacy.We initiated a systematic review to compare the efficacy of SU after failure of Imatinib(IM)in different c-kit mutations.Methods:We searched for sunitinib-treated patients with advanced GISTs after failed IM treatment by using databases such as PubMed,EMBASE,and the Cochrane Library,up to March 2018.We conducted statistical analyses to calculate the odds ratio(OR),hazard ratio(HR)and95%confidence interval(CI)using fixed-effects and random-effects models by Review Manager 5.3 software.Results:We included a total of 474 patients from 3 retrospective studies and 2 cohort studies.Patients with exon 9 mutations had higher clinical benefit(OR=2.61,95%CIs=1.32-5.18,P=0.006)rates and longer progression-free survival(PFS,HR=0.51,95%CIs=0.36—0.72,P=0.0001)compared with exon 11,but there was no statistically significant difference in overall survival(OS,HR=0.93,95%CIs=0.34—2.55,P=0.89)and there was greater heterogeneity(Tau~2=0.72,Chi~2=21.45,df=3,P<0.001,I~2=86%).Subgroup analysis suggests that race may be one of the sources of heterogeneity.Conclusion:The results show that efficacy of SU is closely associated with c-kit genotypes in GISTs.Moreover,racial factor also directly affects the prognosis of different c-kit mutational status,so GISTs patients of different genotypes might also consider the use of targeted drugs in consideration of ethnic differences.