Survival Trend Of Advanced Gastrointestinal Stromal Tumors Treated By Tyrosine Kinase Inhibitors: A 14-Year Single Center Experience

Background: Successful introduction of KIT targeting tyrosine kinase inhibitors (TKIs) and surgical intervention have revolutionized therapy for advanced gastrointestinal stromal tumor (GIST). However, their clinical impact on survival has not been adequately evaluated. Methods: Clinical data of patients who started 1st line imatinib (IM) 400mg/d for metastatic or recurrent GIST at Asan Medical Center between 2001 and 2014 were analyzed and compared between two time periods: 2001-2007 (period 1) and 2008-2014 (period 2). Results: Out of 379 patients, 33.2% and 66.8% were in period 1 and 2. Clinical features were as follow: median age (58.6, 14.6-85.5), male (60.4%), recurred GIST (60.2%), primary tumor (small intestine; 47.2%), liver metastasis (55.9%), baseline median size (51 mm, 0-324), and genotype mutation (KIT exon 11; 70.2%, KIT exon 9; 10.6%, no mutation in KIT or PDGFRA genes; 8.2%, and PDGFRA D842V; 0.8%). There was no significant difference in baseline characteristics between two periods except older age and less wild type in period 2. The objective response rate and disease control rate with IM in all periods were 63.1% and 94.3% and there was also no significant difference between two periods. More patients in period 2 had surgical resection of residual lesions after control with IM (11.9% vs. 24.5%, p = 0.004). With a median follow-up of 6.1 years (yrs) (2.5-16.0) in survivors, median progression-free survival (PFS) was 5.4 yrs (95% confidence interval [CI], 4.0-6.9). For salvage TKIs, more patients in period 2 had sunitinib after failure of high dose IM (p = 0.053) and regorafenib after failure of sunitinib (p = 0.003). Median overall survival (OS) was 8.8 yrs (95% CI, 7.8-9.7). Comparing period 1 and 2, both PFS with IM and OS were significantly longer in period 2 (median PFS, 3.9 yrs vs. not reached, p = 0.002; median OS, 7.2 yrs vs. not reached, p = 0.019, respectively). In multivariate analysis for both PFS and OS, surgical intervention and recent period were favorable prognostic factors whereas older age and large tumor size were poor prognostic factors. Conclusions: Prognosis of advanced GISTs has been improved over recent years with more common use of salvage TKIs and surgical intervention. Legal entity responsible for the study: Asan Medical Center Funding: None Disclosure: All authors have declared no conflicts of interest.