Published on February 26, 2026, this international study represents a major collaboration between The Life Raft Group and thirty-five leading cancer centers across the U.S., Europe, and Japan to better understand treatment for gastrointestinal stromal tumors (GIST) with KIT exon 9 mutations. Researchers analyzed outcomes from 367 patients who had surgery to remove their tumors and examined whether imatinib taken after surgery (adjuvant therapy) improves survival. The study found that patients who received adjuvant imatinib experienced longer time before recurrence and improved overall survival, particularly those at high risk. These results provide the strongest evidence to date supporting adjuvant imatinib for high-risk KIT exon 9 GIST.
From Denisse Evans, Senior Director of Data Management & Research
The Life Raft Group is excited to share our latest study on adjuvant imatinib in KIT exon 9–mutant GISTs, a biologically distinct subset with reduced sensitivity to standard-dose therapy in advanced disease. In our multinational cohort (35 centers, Europe, US, Japan), we applied time-dependent and causal inference models to assess recurrence-free and overall survival.
🔹 Adjuvant imatinib delays recurrence (HR 0.19 early effect)
🔹 Improves overall survival (HR 0.37)
🔹 Benefit is consistent in mNIH high-risk patients
🔹 No clear difference between 400 mg vs 800 mg daily dosing in high-risk patients
These results reinforce adjuvant imatinib for high-risk KIT exon 9 GIST and highlight the need for prospective studies on optimal dose and duration. The Life Raft Group Patient Registry data was used as part of this study. I am grateful to the patients and caregivers who contributed their experiences; their participation creates a lasting legacy of knowledge that advances research in rare GIST subtypes.
Special recognition & gratitude to Dr. Andrea Napolitano for his leadership in advancing care for this rare GIST subgroup.
Abstract
Importance Gastrointestinal stromal tumors (GISTs) harboring KIT exon 9 mutations represent a biologically distinct subgroup with reduced sensitivity to standard-dose imatinib in the advanced setting. The benefit of adjuvant imatinib in this population remains uncertain.
Objective To evaluate the association between adjuvant imatinib and recurrence-free survival (RFS) and overall survival (OS) in patients with resected GISTs with KIT exon 9 mutations.
Design, Setting, and Participants This international, multicenter cohort study included patients with localized, molecularly confirmed GISTs with KIT exon 9 mutations who underwent curative-intent surgery between January 1990 and July 2022 at 35 referral centers in Europe, the US, and Japan, or were registered in the Life Raft Group database. The analysis took place between January 2025 and November 2025.
Exposures Adjuvant imatinib initiated after curative surgery, modeled as a time-dependent covariate to account for immortal time bias.
Main Outcomes and Measures The primary end points were RFS (time from surgery to recurrence or death) and OS (time from surgery to death) in the full cohort and in the high-risk subgroup defined by modified National Institutes of Health (mNIH) criteria. Multivariable Cox regression models included established prognostic covariates and cluster-robust standard errors. Overlap weighting (OW) based on propensity scores was used as a causal inference model. Secondary analyses evaluated 400 mg/d vs 800 mg/d dosing in the mNIH high-risk subgroup.
Results A total of 367 patients were included, 187 (51.0%) male and 180 (49%) female, with a mean (SD) age of 56 (13) years. Among these, 91 (24.8%) were observed and 276 (75.2%) received adjuvant imatinib (median [IQR] duration, 27.3 [13.5-36.0] months; 116 [42.0%] treated ≥3 years). Consistent with a cytostatic activity, adjuvant imatinib in the full cohort was associated with a reduced early hazard of recurrence or death (HR, 0.19; 95% CI, 0.10-0.36), with attenuation over time (time-interaction hazard ratio [HR], 1.85 per log-year). Treatment was also associated with improved OS (HR, 0.37; 95% CI, 0.17-0.83). Similar results were obtained when limiting the analysis to patients with mNIH high-risk disease. OW models and sensitivity analyses confirmed similar associations with RFS and OS. Among 257 patients with mNIH high-risk disease receiving imatinib, no significant difference was observed between 400 mg/d and 800 mg/d dosing.
Conclusion and relevance In this large international cohort study of resected GISTs with KIT exon 9 mutations, adjuvant imatinib was independently associated with delayed recurrence and improved survival. These findings support the use of adjuvant imatinib in mNIH high-risk GISTs with KIT exon 9 mutations and underscore the need for prospective studies to define optimal dosing and treatment duration.
