Treatment of metastatic GIST in a nutshell

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  • Imatinib (400 mg daily) is the standard first-line drug therapy for treatment of locally advanced or metastatic GIST. 
  • Approximately 35% of patients with metastatic GIST harboring mutation in exon 9 of KIT demonstrated objective response to treatment with imatinib in one large trial. 
  • Retrospective analyses of patients with KIT exon 9–mutant GIST crossing over to the higher dose of 400 mg twice daily of imatinib demonstrated significant benefit in approximately 50% of the patients, and dose escalation is a reasonable first step in a patient who has no significant adverse effects on the lower dose. 
  • In a phase I trial of imatinib in patients with sarcoma, dose-limiting toxicities were encountered at daily doses of 1,000 mg. An antitumor advantage of 1,200 mg per day versus 800 mg per day has not been established. 
  • Surgical debulking has not obtained long-term control of GIST in patients with multifocal tumor progression. 
  • Sunitinib is the only drug approved for second-line use in patients with GIST resistant to imatinib or in patients who are intolerant of imatinib.

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