KIT and PDGFRA Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial
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Updated: Aug 4, 2025
Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
Heikki Joensuu1, Eva Wardelmann2, Mikael Eriksson3
1Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Purpose:
Limited data are available about the influence of KIT and PDGFRA mutations on overall survival (OS) of patients with gastrointestinal stromal tumor (GIST) treated with adjuvant imatinib.
Patients And Methods:
The Scandinavian Sarcoma Group XVIII/AIO multicenter trial accrued 400 patients with a high risk for GIST recurrence after macroscopically complete surgery between February 4, 2004, and September 29, 2008. The patients received adjuvant imatinib 400 mg/day for either 1 year or 3 years based on random allocation. We analyzed using conventional sequencing KIT and PDGFRA mutations centrally from 341 (85%) patients who had localized, centrally confirmed GIST, and correlated the results with recurrence-free survival (RFS) and OS in exploratory analyses.
Results:
During a median follow-up time of 10 years, 164 RFS events and 76 deaths occurred. Most patients were re-treated with imatinib when GIST recurred. Patients with KIT exon 11 deletion or indel mutation treated with 3 years of adjuvant imatinib survived longer than patients treated for 1 year [10-year OS 86% versus 64%, respectively; HR, 0.34; 95% confidence interval (CI), 0.15-0.72; P = 0.007], and also had longer RFS (10-year RFS 47% versus 29%; HR, 0.48; 95% CI, 0.31-0.74; P < 0.001). Patients with KIT exon 9 mutation had unfavorable OS regardless of the duration of adjuvant imatinib.
Conclusions:
Compared with 1 year of imatinib, 3 years of adjuvant imatinib led to 66% reduction in the estimated risk of death and a high 10-year OS rate in the subset of patients with a KIT exon 11 deletion/indel mutation.
Insights
Three years of adjuvant imatinib significantly improved survival for gastrointestinal stromal tumor (GIST) patients with KIT exon 11 mutations. This duration of treatment reduced the risk of death by 66% in this specific patient group.
Area of Science:
- Oncology
- Molecular Biology
- Clinical Trials
Background:
- Gastrointestinal stromal tumors (GIST) are rare sarcomas driven by specific genetic mutations.
- Adjuvant imatinib therapy is used to prevent recurrence after surgery for high-risk GIST.
- Limited data exist on the impact of specific mutations on long-term outcomes with adjuvant imatinib.
Purpose of the Study:
- To investigate the influence of KIT and PDGFRA mutations on overall survival (OS) in patients with GIST treated with adjuvant imatinib.
- To correlate specific mutation types with recurrence-free survival (RFS) and OS in a high-risk GIST cohort.
Main Methods:
- Analysis of KIT and PDGFRA mutations in 341 patients from the Scandinavian Sarcoma Group XVIII/AIO trial.
- Patients received adjuvant imatinib for 1 or 3 years post-surgery.
- Exploratory analysis correlating mutations with RFS and OS after a median follow-up of 10 years.
Main Results:
- Patients with KIT exon 11 deletion/indel mutations treated with 3 years of imatinib had significantly longer 10-year OS (86% vs. 64%) and RFS (47% vs. 29%) compared to 1 year.
- A 3-year imatinib regimen reduced the risk of death by 66% in the KIT exon 11 subgroup.
- Patients with KIT exon 9 mutations showed poor OS irrespective of imatinib duration.
Conclusions:
- Three years of adjuvant imatinib significantly improves survival outcomes for GIST patients with KIT exon 11 deletion/indel mutations.
- KIT exon 9 mutations are associated with unfavorable outcomes despite adjuvant imatinib treatment.
- Extended adjuvant imatinib duration is beneficial for a specific subset of GIST patients based on their mutational profile.
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