CHICAGO -- Researchers have found that the same gene mutation responsible for a tepid response to Gleevec (imatinib) in treatment of gastrointestinal stromal tumors (GIST), bestows benefit when a newer targeted therapy, Sutent (sunitinib), is used.
They also discovered that a different GIST tumor mutation predicts the opposite - a better response to Gleevec than to Sutent.
This means, the researchers say, that a single genetic assay could potentially help physicians decide when to switch patients from Gleevec, the first-line treatment, to therapy with Sutent, which the FDA approved for second-line use for this cancer in January 2006.
Results were presented at the first meeting on the Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.
"This is a story about personalized medicine," said the lead researcher, Michael C. Heinrich, M.D., professor of medicine at Oregon Health and Science University. "Treatment isn't one-size-fits-all anymore. We can individualize therapy based on the types of mutations found in tumor cells.
"In the case of GIST, we now understand more about how the mutational status of a patient's tumor predicts response to different targeted therapies."
Gleevec revolutionized the care of GIST, a rare cancer resistant to chemotherapy when advanced. Gleevec blocks the abnormal tyrosine kinase enzyme that plays a role in both chronic myeloid leukemia (CML) and in GIST, for which the drug was approved for use in 2001, and 2002, respectively.
But not all patients respond equally well to Gleevec, and many become resistant. Follow-up studies have found that the various mutations present on the tyrosine kinase enzyme can predict the degree of Gleevec benefit, Heinrich said. For example, 85 percent of GIST patients have a mutation in their tumor cell's c-kit gene, which encodes a tyrosine kinase receptor, and the two-thirds of those
Contact: Warren Froelich
American Association for Cancer Research