Patient status after four years on Gleevec

The 2006 American Society of Clinical Oncology gastrointestinal conference was held in January. Dr. Charles Blanke, Oregon Health & Science University, updated the results of the original phase II trial of Gleevec for GIST. This was the earliest trial and the results represent the most mature response data available.

This trial was for patients with unresectable or metastatic GIST. Many of the patients had very advanced disease.

Even in this advanced stage of GIST, the median overall survival in this trial was 4.8 years. Blanke said that patients with “stable disease” and those that had minor shrinkage that didn’t qualify as a response did just as well as those with a partial response (see Figure 1).

Overall, two-thirds of the patients had a partial response to Gleevec; only 12 percent had initial progression. The median (50 percent of patients) time to response was 12 weeks, however, the time to response varied from three weeks to 171 weeks. Two of the 147 patients had a complete response.

A patient’s mutation status (genotype) was the best predictor of both response and overall survival. Patients with a KIT exon 11 mutation had the best partial response rates (87 percent, see Figure 2) and the longest overall survival (see Figure 3). The median overall survival has not been reached for patients with KIT exon 11 mutations.

Blanke’s conclusions:
— Gleevec is well tolerated and remains the most effective therapy for patients with advanced GIST. — Survival strongly correlates with response or achievement of stable disease.
— The median onset of response is relatively fast (12 weeks); however, 25 percent of patients respond after 23 weeks.
— Drug efficacy is related to kinase genotype.
— Despite the potential emergence of Gleevec resistance, a significant fraction of patients remain on drug long term.