Mutation Analyses and Outcomes With GISTs

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Data suggest that patients whose GIST harbors a KIT exon 11 deletion should receive imatinib for 3 years.
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.

RELATED: Olaratumab May Improve Disease Control in Certain Patients With GIST

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.

Reference

  1. 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]

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