Phase III dose-randomization study of imatinib mesylate (STI571, Gleevac) for GIST: Intergroup S0003 early results

Reviewer: S. Jack Wei, MD
Last Modified: June 1, 2003

Presenter: RS Benjamin
Presenter's Affiliation: Sarcoma Intergroup
Type of Session: Scientific


    Imatinib has been shown to have high rates of activity in most gastro-intestinal stromal tumors (GIST) due to its specific activity against the KIT receptor tyrosine kinase which is frequently up-regulated in GIST. High response rates and durable disease control have been seen with the use of imatinib in GIST. Questions remain regarding the optimal dosage for imatinib in these tumors. 2 parallel studies examining the effect of dose on these tumors were performed by the US Sarcoma Intergroup and the EORTC. This study represents the early results from the US Sarcoma Intergroup.

Materials and Methods

  • 486 patients were treated with imatinib for GIST between 12/00 and 9/01.
  • Patients were eligible for the study if they had documented GIST that was KIT positive and had a ECOG performance status of 0-3.
  • Patients were randomized to 2 arms: 1) 400 mg of daily oral imatinib or 2) 800 mg of daily oral imatinib.
  • Patients were allowed to cross-over from Arm 1 to Arm 2 if they had documented progressive diseaes.
  • Median follow-up with 14 mo.


  • No differences were seen between Arm 1 and Arm 2 for response rate (37% for both arms), response + stable disease (41% vs. 44%), 1 yr progression-free survival (71% vs. 70%), or 6 mo overall survival (91% vs. 92%).
  • 46% of patients in Arm 1 crossed over to Arm 2 due to progressive disease.
  • Overall, 285 patients had ceased treatment due to progressive disease (PD). There was no difference in rate of PD between the 2 arms.
  • A higher rate of grade 3/4 toxicity was seen with the higher dose of imatinib(p<0.0001).

Author's Conclusions

  • Imatinib is highly active against GIST.
  • There is no apparent difference between the two doses of imatinib with regards to patient outcome.
  • The higher dose of imatinib appears to have a somewhat higher rate of toxicity.

Clinical/Scientific Implications

    Imatinib continues to offer strong activity against GIST with KIT tyrosine kinase receptor and should be considered for all patients with these tumors. Although preliminary data showed that 800 mg of imatinib was well-tolerated, there dose not appear to any additional benefit to higher doses, and therefore a dose of 400 mg daily of imatinib should be considered standard. Longer follow-up from this study will help clarify the issue of long-term control of this disease using imatinib.

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.


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