Imatinib (Gleevec®) dose escalation appears to produce similar outcomes as sunitinib when used as second-line therapy in patients with advanced nonKIT exon 9 mutated gastrointestinal stromal tumor (GIST), according to a recently published study in the journal Targeted Oncology.

Imatinib is currently the treatment of choice for patients with GIST who, due to advanced disease, are not eligible for curative intent surgery. In cases in which imatinib proves to be ineffective, sunitinib is currently the treatment of choice. Although some authors suggest that a high dose of 800 mg of imatinib could also be a suitable second-line therapy alternative, there are no studies comparing the 2 treatments, Mahmoud Mohammadi, of the Leiden University Medical Center in the Netherlands, and colleagues noted.

Therefore, the authors aimed to compare sunitinib to high-dose imatinib through a retrospective, multicenter study including data from over 100 patients. The primary outcome measures of the study were progression-free survival and overall survival. 

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Patients that received initial first-line therapy with drugs different from imatinib were excluded from the study. The reason for stopping initial imatinib therapy was disease progression in all cases.

Of the patients included in the study, 65% received sunitinib and 35% received 800 mg of imatinib after the failure of initial therapy. Among the 2 groups, there was no significant difference in baseline characteristics such as metastasis, mitotic rate, or tumor location, nor was there a significant difference regarding initial therapy duration. Median follow-up in the sunitinib group and the high-dose imatinib group was 55 and 46 months, respectively.

Results revealed that both groups had similar rates of disease progression, approximately 89% in both cases. Furthermore, progression-free survival was similar in both groups: 8 months in the sunitinib group and 5.6 months in the imatinib group. 

Over 65% of patients died during the follow-up period, and overall survival was also similar between both groups, with both having approximately 63 months of overall survival.

“In conclusion, this study demonstrates that in patients with advanced GIST harboring a nonKIT exon 9 mutation, imatinib dose escalation could serve as a proper alternative second-line strategy for sunitinib after failure on imatinib 400 mg,” the authors concluded. 


Mohammadi M, Jansen-Werkhoven T, et al. Dutch gastrointestinal stromal tumor (GIST) registry data comparing sunitinib with imatinib dose escalation in second-Line advanced non-KIT exon 9 mutated GIST patients. Targ Oncol. Published online November 14, 2022. doi:10.1007/s11523-022-00926-6