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

Joensuu, Heikki; Wardelmann, Eva; Eriksson, Mikael; Reichardt, Annette; Hall, Kirsten Sundby; Schütte, Jochen; Cameron, Silke; Hohenberger, Peter; Sihto, Harri; Jost, Philipp J; Lindner, Lars H; Bauer, Sebastian; Nilsson, Bengt; Kallio, Raija; Pesonen, Tommi; Reichardt, Peter

doi:10.1158/1078-0432.CCR-22-3980

2023

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Title:: KIT and PDGFRA Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial.
Document type:: Article; Multicenter Study; Randomized Controlled Trial; Journal Article; Research Support, Non-U.S. Gov't
Author(s):: Joensuu, Heikki; Wardelmann, Eva; Eriksson, Mikael; Reichardt, Annette; Hall, Kirsten Sundby; Schütte, Jochen; Cameron, Silke; Hohenberger, Peter; Sihto, Harri; Jost, Philipp J; Lindner, Lars H; Bauer, Sebastian; Nilsson, Bengt; Kallio, Raija; Pesonen, Tommi; Reichardt, Peter
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.
Journal title abbreviation:: Clin Cancer Res
Year:: 2023
Journal volume:: 29
Journal issue:: 17
Pages contribution:: 3313-3319
Fulltext / DOI:: doi:10.1158/1078-0432.CCR-22-3980
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/37014660
Print-ISSN:: 1078-0432
TUM Institution:: Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie (Prof. Bassermann)
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie (Prof. Bassermann)2023