Preventative Gleevec for GIST

There is no approved form of adjuvant treatment for GIST. Adjuvant Gleevec remains an investigational treatment. However, many GIST patients in the United States take Gleevec on an adjuvant basis (off-label, however; some insurance companies will not pay for off-label use). We understand that this is far less common in other countries. Novartis is working with the Food and Drug Administration (FDA) to try to obtain U. S. approval of Gleevec for adjuvant therapy 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 is ending immediately.

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.

Trial organizers will be working with investigators at the many trial sites on a method to notify patients about these developments. The trial investigators will notify patients whether they received Gleevec or a placebo. Patients that were receiving placebo when the trial was stopped will be given the opportunity to receive one year of Gleevec at no cost to them.

Many 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?
• 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.