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Kinase genotype of gastrointestinal stromal tumor affected treatment outcome

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Patients with advanced gastrointestinal stromal tumor with KIT exon 11 mutations may have a superior outcome after treatment with imatinib (Gleevec, Novartis), compared with patients with KIT exon 9 mutations.

According to researchers from the Cancer and Leukemia Group B and the Southwest Oncology Group, a relationship exists between kinase genotype of gastrointestinal stromal tumor and imatinib treatment outcome.

The researchers examined the link in the North American phase-3 study SWOG S0033/CALGB 150105. The trial included 428 patients with CD117-positive gastrointestinal stromal tumors who were randomly assigned to imatinib 400 mg or 800 mg per day.

According to the researchers, KIT exon 11-mutant genotype (n=283) was related to improved outcome compared with KIT exon 9-mutant genotype (n=32) and wild-type (n=67) genotypes. Patients with KIT exon 11 genotype had a complete response/partial response rate of 71.7% vs. 44.4% for patients with KIT exon 9 genotype and 44.6% of patients with wild-type genotypes (P=.0002).

KIT exon 11-mutant genotype was also associated with improved time to tumor progression (median 24.7 months vs. 16.7 months for exon 9 and 12.8 months for wild-type) and OS (median 60 months vs. 38.4 months for exon 9 and 49 months for wild-type).

According to the researchers, imatinib dose did not affect survival outcomes among patients with exon 9-mutant, exon 11-mutant or wild-type genotypes. However, patients with exon 9-mutant tumors assigned to imatinib 800 mg had improved response rates compared with those assigned to the 400-mg dose (complete response/partial response, 67% vs. 17%; P=.02). – by Stacey L. Adams

J Clin Oncol. 2008;doi:10.1200/JCO.2008.17.4284

This study shows that you can look at the genetic features of GIST and predict who gets the most benefit and who gets somewhat less benefit based on the genotype. That is important, but it would be more valuable if you knew that alternate therapies would make sense in these same patients. The dilemma right now is that the study didn’t look at selecting patients by genotype and also choosing therapy by genotype; that’s the next step.

– Alan P. Venook, MD

HemOnc Today Editorial Board member