Dataset Information

KIT and PDGFRA Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial.

ABSTRACT:

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.

SUBMITTER: Joensuu H

PROVIDER: S-EPMC10472091 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

KIT and PDGFRA Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial.

Joensuu Heikki H Wardelmann Eva E Eriksson Mikael M Reichardt Annette A Hall Kirsten Sundby KS Schütte Jochen J Cameron Silke S Hohenberger Peter P Sihto Harri H Jost Philipp J PJ Lindner Lars H LH Bauer Sebastian S Nilsson Bengt B Kallio Raija R Pesonen Tommi T Reichardt Peter P

Clinical cancer research : an official journal of the American Association for Cancer Research 20230901 17

<h4>Purpose</h4>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.<h4>Patients and methods</h4>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 ...[more]

PMID: 37014660

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Project description:ImportanceLittle is known about whether the duration of adjuvant imatinib influences the prognostic significance of KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor α (PDGFRA) mutations.ObjectiveTo investigate the effect of KIT and PDGFRA mutations on recurrence-free survival (RFS) in patients with gastrointestinal stromal tumors (GISTs) treated with surgery and adjuvant imatinib.Design, setting, and participantsThis exploratory study is based on the Scandinavian Sarcoma Group VIII/Arbeitsgemeinschaft Internistische Onkologie (SSGXVIII/AIO) multicenter clinical trial. Between February 4, 2004, and September 29, 2008, 400 patients who had undergone surgery for GISTs with a high risk of recurrence were randomized to receive adjuvant imatinib for 1 or 3 years. Of the 397 patients who provided consent, 341 (85.9%) had centrally confirmed, localized GISTs with mutation analysis for KIT and PDGFRA performed centrally using conventional sequencing. During a median follow-up of 88 months (completed December 31, 2013), 142 patients had GIST recurrence. Data of the evaluable population were analyzed February 4, 2004, through December 31, 2013.Main outcomes and measuresThe main outcome was RFS. Mutations were grouped by the gene and exon. KIT exon 11 mutations were further grouped as deletion or insertion-deletion mutations, substitution mutations, insertion or duplication mutations, and mutations that involved codons 557 and/or 558.ResultsOf the 341 patients (175 men and 166 women; median age at study entry, 62 years) in the 1-year group and 60 years in the 3-year group), 274 (80.4%) had GISTs with a KIT mutation, 43 (12.6%) had GISTs that harbored a PDGFRA mutation, and 24 (7.0%) had GISTs that were wild type for these genes. PDGFRA mutations and KIT exon 11 insertion or duplication mutations were associated with favorable RFS, whereas KIT exon 9 mutations were associated with unfavorable outcome. Patients with KIT exon 11 deletion or insertion-deletion mutation had better RFS when allocated to the 3-year group compared with the 1-year group (5-year RFS, 71.0% vs 41.3%; P < .001), whereas no significant benefit from the 3-year treatment was found in the other mutational subgroups examined. KIT exon 11 deletion mutations, deletions that involved codons 557 and/or 558, and deletions that led to pTrp557_Lys558del were associated with poor RFS in the 1-year group but not in the 3-year group. Similarly, in the subset with KIT exon 11 deletion mutations, higher-than-the-median mitotic counts were associated with unfavorable RFS in the 1-year group but not in the 3-year group.Conclusions and relevancePatients with KIT exon 11 deletion mutations benefit most from the longer duration of adjuvant imatinib. The 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.Trial registrationclinicaltrials.gov Identifier: NCT00116935.

Dataset Information

KIT and PDGFRA Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial.

Purpose

Patients and methods

Results

Conclusions

Publications

KIT and PDGFRA Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial.

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