Optimal adjuvant imatinib duration influenced by KIT mutation status
medwireNews: Patients with gastrointestinal stromal tumors (GISTs) harboring KIT proto-oncogene receptor tyrosine kinase exon 11 deletion mutations derive the greatest benefit from 3 years of adjuvant imatinib treatment, researchers report.
Patients with other mutations, including those in the platelet-derived growth factor receptor α (PDGFRA) gene, showed no significant benefit of receiving 3 years of imatinib compared with 1 year of treatment.
This suggests that “physicians who are considering a recommendation of adjuvant therapy for resected primary GIST should first determine the genotype of the patient’s tumor,” say Michael Heinrich (Portland Veterans Affairs Health Care System, Oregon, USA) and co-authors of an editorial discussing the findings published in JAMA Oncology.
The study included 341 patients with GISTs who were treated with surgery and randomly assigned to receive adjuvant imatinib 400 mg daily for 1 or 3 years as part of the Scandinavian Sarcoma Group VIII/Arbeitsgemeinschaft Internistische Onkologie (SSGXVIII/AIO) multicenter clinical trial.
The majority (80.4%) of patients had GISTs with a KIT mutation, most commonly exon 11 deletion or insertion-deletion mutations (54.4%). A further 12.6% had GISTs that harbored a PDGFRA mutation, and 7.0% had GISTs that were wild type for these genes.
During a median follow-up period of 88 months, 46% of 174 patients treated with imatinib for 1 year, and 37% of 167 treated for 3 years, experienced disease progression or died.
When the researchers, led by Heikki Joensuu (University of Helsinki, Finland), investigated the impact of the gene mutations on recurrence-free survival (RFS), they found that patients with KIT exon 11 deletion or insertion-deletion mutations had significantly better 5-year RFS when allocated to the 3-year group compared with the 1-year group, at 71.0% versus 41.3%.
By contrast, no significant benefit from the 3-year treatment was found in the other mutational subgroups examined.
The team also found that although patients with KIT exon 11 deletion or insertion-deletion mutations had significantly worse RFS than patients without these mutations overall, the prognostic significance of the different types of KIT exon 11 deletion mutations on RFS depended on the duration of adjuvant imatinib administered.
Specifically, such mutations were significantly associated with unfavorable RFS in patients assigned to 1 year of imatinib treatment, but not in those assigned to 3 years of treatment.
This suggests that “[t]he duration of adjuvant imatinib modifies the risk of GIST recurrence associated with some KIT mutations, including deletions that affect exon 11 codons 557 and/or 558,” Joensuu and co-authors conclude.
Given the findings, Heinrich and co-authors recommend that “all patients with high-risk GIST and any type of activating KIT exon 11 mutation should be offered at least 3 years of adjuvant imatinib,” but add that “the optimal duration of therapy remains unknown.”
By Laura Cowen
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