Patients (pts) with advanced GIST harbouring the KIT exon 9 mutation have a better progression-free survival (PFS) on a higher daily dose level, i.e. 800 mg of imatinib (IM), which is therefore held as standard treatment in this subgroup. This schedule in the adjuvant setting has been subsequently proposed despite the lack of any controlled trials.
We retrospectively evaluated characteristics of pts with KIT exon 9 mutated GIST in 6 different centers in France and Spain, treated with a daily dose of 400 mg of IM. Pts with localized and advanced GIST were separately analyzed: Kaplan-Meier and Cox proportional hazards model analyses were used to compare median relapse-free survival (mRFS) and OS (mOS) in the adjuvant setting, and overall response rate (ORR), median PFS to IM 400 mg (mPFS), median time to IM failure (mTIF) defined as time to 2nd progression (PD) or death, and mOS in the advanced setting.
We identified 43 pts (44% of males) with a median age of 56 yrs (16-78). 67.4% of GIST was originated in the small bowel and 18.6% in the stomach. In adjuvant situation (31 pts), 42% of pts had a high risk (HR) of relapse (Miettinen classification) and 29% an intermediate risk (IR). 17 out of 31 pts received adjuvant 400 mg/d of IM for a median duration of 21 months (m). The mRFS of pts receiving adjuvant IM was 82 m vs 21 m for those who did not. In the advanced setting, 22 pts were treated with 400 mg of IM. The ORR was 37% (3 CR and 5 PR), with additional 7 stabilizations (benefit in 69% of pts). At PD, 77% of pts received the higher dose IM regimen (800 mg). The mPFS was 12.7 m (CI 95% 6.8-18.6) and the mTIF was 20.6 m (CI 95% 12.2-29). The mOS was 42.9 m. No prognostic variable (gender, age, PS, site of primary disease, diameter of largest lesion, prior surgery of primary) was significantly related with mOS or mTIF.
Despite the limitations of retrospective analysis and the small number of pts, benefit of adjuvant IM (400 mg/d) in pts with localized GIST harbouring KIT exon 9 mutations seems relevant. Pts with advanced GIST initially treated with 400 mg of IM have a similar outcome in terms of mTIF (20 m) than those receiving high-dose IM upfront (19 m in the initial MetaGIST trial, M.V. Glabbeke et al, JCO 2010).
Clinical trial identification
Legal entity responsible for the study
Gustave Roussy Institute.
Has not received any funding.
All authors have declared no conflicts of interest.