Preventative Gleevec for GIST

On December 19th, 2008, the Federal Drug Administration (FDA) approved adjuvant treatment for GIST in the United States. Adjuvant Gleevec is not yet approved in other countries. U. S. approval of Gleevec for adjuvant therapy was based on the interim results of the Z9001 phase III adjuvant Gleevec trial.

On April 12th 2007, the American College of Surgeons announced that the phase III trial for Gleevec in treating patients with primary GIST that has been completely removed by surgery (the "Z9001" trial) has successfully met its endpoint. The trial began recruiting GIST patients in 2002 and ended in April, 2007.

This was a very large trial, with hundreds of sites in North America participating. The trial was a double-blind, randomized trial that looked at GIST patients that had their primary tumors completely removed by surgery. The primary tumor had to be 3 cm or greater in size. Patients were then randomized to receive either 400 mg of Gleevec for one year or a placebo for one year. The intent was to see if taking Gleevec for one year delayed or prevented the recurrence of GIST.

In April 2007, an independent data-monitoring committee announced that the trial had crossed the previously established boundary for recurrence-free survival and had thus met its primary endpoint with a highly significant hazard ratio of 3.1. The interim analysis showed a 97 percent recurrence-free survival rate for the Gleevec group as opposed to an 83 percent recurrence-free survival rate for those on the placebo. Taking Gleevec for one year after surgery significantly increased the time before a GIST recurrence. At this time no difference in overall survival has been noted between the two groups.
Note: Length of follow-up was not given.

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Some questions remain about the use of adjuvant Gleevec such as:

• Will Gleevec prevent a recurrence or just delay a recurrence?
• Will longer follow-up reveal a survival benefit?
• What is the optimum duration of adjuvant Gleevec? In the clinical trial that resulted in adjuvant Gleevec approval, the duration of treatment was one year. Other trials are underway that examine longer duration of treatment (up to 3 years).
• Should patients with exon 9 tumors take higher doses of Gleevec for adjuvant therapy?
• Are there some subsets of patients that might not benefit from adjuvant Gleevec?
• Should patients with low-risk tumors take adjuvant Gleevec?

Readers interested in exploring these questions further are referred to the links at the bottom of this page.