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Role of adjuvant imatinib dose in radically resected GIST harboring KIT exon 9 mutations

Authors :
Heikki Joensuu
Elena Fumagalli
Peter Hohenberger
Margherita Nannini
Angelo Paolo Dei Tos
Silvia Gasperoni
Javier Martin Broto
Sebastian Bauer
Andrea Napolitano
Piotr Rutkowski
Tommaso De Pas
Giovanni Grignani
Bruno Vincenzi
Alessandro Gronchi
Giuseppe Badalamenti
Nadia Hindi
Antonella Brunello
Antoine Italiano
Robin L. Jones
Spyridon Gennatas
Publication Year :
2020

Abstract

11533 Background: Gastrointestinal stromal tumors (GIST) with a driver mutation in KIT exon 9 (Ex9) represent about 10% of all newly diagnosed cases. In the metastatic setting, Ex9-mutated GIST patients benefit from higher doses of imatinib (800 mg/day vs standard 400 mg/day). The additional therapeutic benefit from a higher dose of imatinib in the adjuvant setting in this molecular subgroup has not been confirmed. Methods: We retrospectively identified 105 patients (pts) with resected Ex9-mutated GIST treated with adjuvant imatinib (800 mg/day or 400 mg/day) in 15 different European centers. Disease-Free Survival (DFS) and Imatinib Failure-Free Survival (IFFS) were calculated and analyzed according to the daily dose of imatinib and relevant clinical and pathological variables. Kaplan–Meier curves were used to estimate survival in univariate analyses, and the log-rank test was used to compare the groups. Hazard Ratios (HR) with 95% confidence intervals (CI) were calculated using a univariable Cox model. A multivariate Cox regression model was also performed. Results: Of the 105 pts who met the inclusion criteria, 69 (65.7%) were treated with 400 mg/day and 36 (34.3%) with 800 mg/day. The risk score (AFIP-Miettinen criteria) between the two dose groups was not statistically different (P = 0.29). Median DFS was 73.0 months (mo) in the 400 mg/day group and 61.9 mo in the 800 mg/day group (HR = 0.82, 95% CI: 0.47-1.47; P = 0.50). Median IFFS was 156.8 mo in the 400/day mg group and 117.4 mo in the 800 mg/day group (HR = 0.66, 95% CI: 0.34-1.29; P = 0.19). In a multivariable analysis, the variables statistically associated with DFS were mitotic count, the longest tumor diameter and the duration of adjuvant therapy. Mitotic count and the duration of adjuvant therapy were also associated with IFFS. Importantly, the daily imatinib dose was not associated with survival in either analysis (Table). Conclusions: This is the largest reported cohort of pts with Ex9-mutated GIST treated with either the 400 mg/day or the 800 mg/day dose of adjuvant imatinib. Although retrospective in nature, the data confirm the prognostic value of mitotic count and suggest that patients with Ex9-mutated GIST derive no additional survival benefit from the 800 mg/day dose. [Table: see text]

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....064da307fa5079190beb9915e8ba539b