Mutation Analyses and Outcomes With GISTs
Data suggest that patients whose GIST harbors a KIT exon 11 deletion should receive imatinib for 3 years.
KIT deletion mutations are associated with recurrence-free survival (RFS) among patients with localized gastrointestinal stromal tumors (GISTs) who underwent surgery and received adjuvant imatinib, according to a study published in JAMA Oncology.1
The purpose of this study (ClinicalTrials.gov Identifier: NCT00116935) was to evaluate the effect of KIT or PDGFRA mutations on RFS among patients with GISTs treated with adjuvant imatinib.
This exploratory analysis of a multicenter clinical trial included data from 397 patients from the Scandinavian Sarcoma Group VIII who had undergone surgery for GIST and had a high risk of recurrence. Patients were randomly assigned to receive 1 or 3 years of adjuvant imatinib.
Of 341 patients with a localized GIST, 80.4% harbored KIT mutations and 12.6% PDGFRA mutations.
Recurrence was reported among 142 patients during a median follow-up of 88 months. Presence of KIT exon 11 deletion or insertion-deletion was significantly associated with better 5-year RFS among patients who receive imatinib for 3 years (71%) compared with 1 year (41.3%; P < .001).
An RFS benefit was not found among patients with other KIT or PDGFRA mutations.
Poor 1-year, but not 3-year, RFS was associated with KIT 11 deletions, deletions of codons 557 and/or 558, and deletions that led to the pTrp557_Lys558del variant.
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These data suggest that patients whose GIST harbors a KIT exon 11 deletion should receive imatinib for 3 years. Ongoing trials are evaluating whether a longer duration of imatinib will provide additional benefit.
- Joensuu H, Wardelmann E, Sihto H, et al. Effect of KIT and PDGFRA mutations on survival in patients with gastrointestinal stromal tumors treated with adjuvant imatinib. An exploratory analysis of a randomized clinical trial. JAMA Oncol. 2017 Mar 23. doi: 10.1001/jamaoncol.2016.5751 [Epub ahead of print]