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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 LU orcid ; Reichardt, Annette ; Hall, Kirsten Sundby ; Schütte, Jochen ; Cameron, Silke ; Hohenberger, Peter ; Sihto, Harri and Jost, Philipp J. , et al. (2023) In Clinical Cancer Research 29(17). p.3313-3319
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... (More)

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.

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organization
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type
Contribution to journal
publication status
published
subject
in
Clinical Cancer Research
volume
29
issue
17
pages
7 pages
publisher
American Association for Cancer Research
external identifiers
  • pmid:37014660
  • scopus:85167824855
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-22-3980
language
English
LU publication?
yes
id
4145c758-b486-44e6-b48b-c0ea25b97f6d
date added to LUP
2024-01-12 14:25:24
date last changed
2024-04-13 08:35:45
@article{4145c758-b486-44e6-b48b-c0ea25b97f6d,
  abstract     = {{<p>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 &lt; 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.</p>}},
  author       = {{Joensuu, Heikki and Wardelmann, Eva and Eriksson, Mikael and Reichardt, Annette and Hall, Kirsten Sundby and Schütte, Jochen and Cameron, Silke and Hohenberger, Peter and Sihto, Harri and Jost, Philipp J. and Lindner, Lars H. and Bauer, Sebastian and Nilsson, Bengt and Kallio, Raija and Pesonen, Tommi and Reichardt, Peter}},
  issn         = {{1078-0432}},
  language     = {{eng}},
  number       = {{17}},
  pages        = {{3313--3319}},
  publisher    = {{American Association for Cancer Research}},
  series       = {{Clinical Cancer Research}},
  title        = {{KIT and PDGFRA Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial}},
  url          = {{http://dx.doi.org/10.1158/1078-0432.CCR-22-3980}},
  doi          = {{10.1158/1078-0432.CCR-22-3980}},
  volume       = {{29}},
  year         = {{2023}},
}