Clinical Efficacy Of Third-Line Tyrpsine Kinase Inhibitors For Advanced Gastrointestinal Stromal Tumors After Failure Of Imatinib And Sunitinib:a Meta-Analysis

Background:Until now, only imatinib and sunitinib have proven clinical benefit in patients with gastrointestinal tromal tumours (GIST), but almost all metastatic GIST eventually develop resistance to these agents, resulting in fatal disease progression. We aimed to assess efficacy of regorafenib, nilotiniband imatinib resumption in patients with metastatic or unresectable GIST progressing after failure of at least imatinib and sunitinib.Methods:Randomized controlled trials evaluating the clinical efficacy of TKIs were identified by searching PubMed, Cochrane Database, CNKI and CMB from 2000 to February 2015. Outcomes subjected to analysis were progression-free surviva(PFS) and overall survival(OS). Statistical analyses were performed using Review Manager version 5.3 (Cochrane Collaboration,Oxford, UK) and STATA version 12.0 (Stata Corporation,College Station,TX,USA). Weighted hazard ratios (HR) with 95% confidence intervals (CIs) were calculated for the outcomes.Results:A literature search was performed and yielded a total of 3 RCT include 528 GIST patients who failed the treatment of imatinib and sunitinib.339 received TKIs (regorafenib, nilotinib, or imatinib) and 189 controls received placebo or best supportive care. Progression-free survival was significantly improved in the TKI-treated group (HR 0.42,95% CI 0.253-0.699, p=0.001). No statistically significant difference was detected in overall survival between the treatment group and the control group (HR 0.85; 95%CI 0.71-1.03; P=0.211).Conclusion:The-third-line TKIs (regorafenib, nilotinib, and imatinib) are effective in improving progression-free survival but not overall survival in patients with GIST who failed the treatment of imatinib and sunitinib.