April 2012

Masatinib mesylate in imatinib-naive locally advanced or metastatic gastrointestinal stromal tumor

Abstract 10507, Axel Le Cesne, MD, Institut Gustave Roussy, Villejuif, France

Thirty patients are reported in this Phase II trial analysis. Results indicate a favorable
comparison with imatinib as a first-line treatment for GIST. The definitive answers
regarding this drug should come from the Phase III first-line study of masatinib versus
imatinib which is now recruiting in the United States and Europe. It was reported that one
patient with a PDGFRa D842V mutation had prolonged stable disease and was able to
achieve surgical remission. Also reported were earlier results of in vitro tests that show
masatinib is two to three times more effective against GIST exon 9, 13 and PDGFRa
mutations in a cell proliferation assay. These mutations are less frequent but are often the
source of primary resistance to imatinib.

Because of the small patient population (30) in this study (which is compared to the
Phase III U.S. and European studies of 694 and 946 patients taking imatinib) the results
have to be viewed with caution. For example, the 95 percent confidence interval of the
reported 60 percent two year progression-free survival was 38 percent to 76 percent.
Also, the mutation analysis is partial (15 patients available) and indicates a
preponderance of exon 11 and no exon 9. (A preponderance of exon 11 would improve
the comparative results since exon 11 patients are historically the best responders to this
type of TKI) This highlights the issue of selection bias that can potentially occur in GIST
studies where mutation analysis is not complete.

In an interesting aside, Dr. Le Cesne reported metabolic response was more accurately
analyzed using Dynamic Contrast Enhanced Ultra-Sound (DCE-US) imaging versus
PET.

Abstract #: 10507