Adjuvant Imatinib in Patients with GIST Harboring Exon 9 KIT Mutations: Results from a Multi-institutional European Retrospective Study.

Abstract

PURPOSE:

The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9-mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopathologic variables with survival was evaluated in a large multi-institutional European cohort.

EXPERIMENTAL DESIGN:

Data from 185 patients were retrospectively collected in 23 European GIST reference centers. Propensity score matching (PSM) and inverse-probability of treatment weighting (IPTW) were used to account for confounders. Univariate and multivariate unweighted and weighted Cox proportional hazard regression models were estimated for relapse-free survival (RFS), modified-RFS (mRFS) and imatinib failure-free survival (IFFS). Univariate Cox models were estimated for overall survival.

RESULTS:

Of the 185 patients, 131 (70.8%) received a starting dose of 400 mg/d and the remaining 54 (29.2%) a dose of 800 mg/d. Baseline characteristics were partially unbalanced, suggesting a potential selection bias. PSM and IPTW analyses showed no advantage of imatinib 800 mg/d. In the weighted multivariate Cox models, high-dose imatinib was not associated with the survival outcomes [RFS: hazard ratio (HR), 1.24; 95% confidence interval (CI), 0.79-1.94; mRFS: HR, 1.69; 95% CI, 0.92-3.10; IFFS: HR, 1.35; 95% CI, 0.79-2.28]. The variables consistently associated with worse survival outcomes were high mitotic index and nongastric tumor location.

CONCLUSIONS:

In this retrospective series of patients with KIT exon 9-mutated GIST treated with adjuvant imatinib, a daily dose of 800 mg versus 400 mg did not show better results in terms of survival outcomes. Prospective evaluation of the more appropriate adjuvant treatment in this setting is warranted.

• Authors: Bruno Vincenzi, Andrea Napolitano, Marta Fiocco, Olivier Mir, Piotr Rutkowski, Jean-Yves Blay, Peter Reichardt, Heikki Joensuu, Elena Fumagalli, Spyridon Gennatas, Nadia Hindi, Margherita Nannini, Mariella Spalato Ceruso, Antoine Italiano, Giovanni Grignani, Antonella Brunello, Silvia Gasperoni, Tommaso De Pas, Giuseppe Badalamenti, Maria A Pantaleo, Winan J van Houdt, Nikki S IJzerman, Neeltje Steeghs, Hans Gelderblom, Ingrid M E Desar, Johanna Falkenhorst, Marianna Silletta, Marta Sbaraglia, Giuseppe Tonini, Javier Martin-Broto, Peter Hohenberger, Axel Le Cesne, Robin L Jones, Angelo P Dei Tos, Alessandro Gronchi, Sebastian Bauer, Paolo G Casali
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 28 Issue 8 Pg. 1672-1679 (04 14 2022) ISSN: 1557-3265 [Electronic] United States
• PMID: 34615721 (Publication Type: Journal Article)
• Copyright: ©2021 The Authors; Published by the American Association for Cancer Research.

Chemical References

• Adjuvants, Immunologic
• Antineoplastic Agents
• Imatinib Mesylate
• Proto-Oncogene Proteins c-kit

Topics

• Adjuvants, Immunologic (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Chemotherapy, Adjuvant
• Exons (genetics)
• Gastrointestinal Stromal Tumors (drug therapy, genetics, pathology)
• Humans
• Imatinib Mesylate (therapeutic use)
• Mutation
• Neoplasm Recurrence, Local (drug therapy)
• Proto-Oncogene Proteins c-kit (genetics)
• Retrospective Studies