Clinical outcomes of resected gastrointestinal stromal tumors treated with 3 years of adjuvant imatinib in different genotypes.

Abstract

839 Background: Surgical resection followed by 3 years of adjuvant imatinib is standard for high-risk resectable gastrointestinal stromal tumors (GISTs) defined by modified NIH criteria. However, the impact of different genotypes in this clinical setting is not clearly defined. Methods: We conducted a single-center retrospective study of 468 patients with high-risk resectable GIST who underwent curative resection between 1994 and 2016 in Korea. Among them, 255 received 3 years of adjuvant imatinib and 213 did not. Recurrence-free survival (RFS) in different genotypes was assessed using Kaplan–Meier estimates, log-rank tests, and Cox regression models. Landmark and dynamic landmark analyses were applied to evaluate the time-varying effects of adjuvant therapy. Results: Baseline characteristics were comparable between adjuvant and no adjuvant groups. Among 468 patients ( KIT exon 11: 187 [73.3%] vs. 163 [76.5%], KIT exon 9: 36 [14.1%] vs. 22 [10.3%], wild-type [WT]: 23 [9.0%] vs. 20 [9.4%], other mutations: 9 [3.5%] vs. 8 [3.8%] in adjuvant vs. no adjuvant groups, respectively), three years of adjuvant imatinib significantly improved RFS in the overall cohort (Hazard Ratio [HR] 0.33; 95% CI, 0.27–0.42; p < 0.001). Subgroup analyses showed consistent RFS benefit in patients with KIT exon 11 (HR 0.32; 95% CI, 0.25–0.42), KIT exon 9 mutations (HR 0.32; 95% CI, 0.18–0.58), and WT GISTs (HR 0.33; 95% CI, 0.13–0.72). For other mutations, adjuvant imatinib showed a trend toward improved RFS, although without statistical significance (p=0.089). Five-year RFS rates were also higher with adjuvant imatinib across different genotypes: KIT exon 11 (59.9% vs. 22.0%, p<0.001), KIT exon 9 (27.8% vs. 4.6%, p<0.001), WT (69.6% vs. 29.2%, p=0.004). Landmark analysis revealed a marked reduction in recurrence risk during treatment (HR 0.17; 95% CI, 0.12–0.24; p<0.001), particularly in KIT exon 11 mutations (HR 0.12; 95% CI, 0.07–0.18) and exon 9 mutations (HR 0.29; 95% CI, 0.14–0.60). However, the HR for RFS increased after imatinib discontinuation at 3 years (HR 0.70; 95% CI, 0.49– 1.00), with this pattern most evident in KIT exon 11 mutations (HR 0.77; 95% CI, 0.51–1.15). Conclusions: Three years of adjuvant imatinib treatment following surgical resection of GIST provides benefit not only for GISTs with KIT exon 11 mutations, but also for GISTs with other genotypes, such as KIT exon 9 mutations and WT.