Higher Imatinib Dose Better in GIST Pts With Exon 9 Mutation

LEUVEN, Belgium—A higher, investigational starting dose of imatinib (Gleevec) significantly improved progression-free survival (PFS) in high-risk patients with advanced KIT-positive gastrointestinal stromal tumor (GIST) expressing the exon 9 mutation, according to a new analysis of an EORTC phase III trial. The trial compared imatinib at the standard dose of 400 mg/d vs 800 mg/d in patients with unresectable and/or metastatic GIST. Researchers analyzed pretreatment GIST samples for mutations from 377 patients in the trial.

The presence of a KIT exon 9 mutation was the strongest adverse prognostic factor for response to imatinib, increasing relative risk of disease progression by 171% (P < .0001), compared with KIT exon 11 mutations. In patients with the exon 9 mutation, the higher dose resulted in superior PFS (P = .0013), with a relative risk reduction of 61% (Eur J Cancer 42:1093-1103, 2006).