Kinase mutations and efficacy of imatinib in Korean patients with advanced gastrointestinal stromal tumors.

Abstract

PURPOSE:

This study analyzed the relationship between treatment outcome and kinase mutational status in Korean patients with advanced gastrointestinal stromal tumors (GISTs).

EXPERIMENTAL DESIGN:

Clinical data were collected from 113 consecutive patients with metastatic or unresectable GISTs treated with imatinib from June 2001 through June 2005 at five institutions in Korea. KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were examined.

RESULTS:

The median patient age was 57 years (range, 31-82 years). The overall response rate was 67.2%. KIT mutations were found in exon 11 (n = 92, 81.4%) and exon 9 (n = 10, 8.8%). One patient had a PDGFRA exon 18 mutation. The overall mutation rate was 91.2%. Response rates were 68.4%, 50.0%, and 80.0% in patients with KIT exon 11 mutations, KIT exon 9 mutations, and no kinase mutations, respectively. With a median follow-up of 49.0 months, the median progression-free survival (PFS) time was 42.0 months and median overall survival (OS) time was not reached. PFS and OS times did not differ significantly according to KIT genotype.

CONCLUSION:

This study was unable to find an association between KIT mutational status and clinical outcome of imatinib in Korean patients with advanced GISTs. There was a trend toward better outcomes for patients with wild-type KIT or exon 11 mutations compared with exon 9 mutations, although this was not statistically significant. Compared with previous studies in western populations, these results suggest that ethnic differences may influence the relationship between KIT genotype and clinical outcome to imatinib.

• Authors: Tae Won Kim, Min-Hee Ryu, Heungnam Lee, Sun Jin Sym, Jae-Lyun Lee, Heung Moon Chang, Young Suk Park, Kyung Hee Lee, Won Ki Kang, Dong Bok Shin, Yung-Jue Bang, Jung Shin Lee, Yoon-Koo Kang
• Journal: The oncologist (Oncologist) Vol. 14 Issue 5 Pg. 540-7 (May 2009) ISSN: 1549-490X [Electronic] England
• PMID: 19411681 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzamides
• Piperazines
• Pyrimidines
• Imatinib Mesylate
• Receptor, Platelet-Derived Growth Factor alpha
• Proto-Oncogene Proteins c-akt

Topics

• Adult
• Aged
• Aged, 80 and over
• Benzamides
• Exons
• Female
• Gastrointestinal Stromal Tumors (drug therapy, genetics, mortality)
• Genotype
• Humans
• Imatinib Mesylate
• Male
• Middle Aged
• Mutation
• Piperazines (therapeutic use)
• Proto-Oncogene Proteins c-akt (genetics)
• Pyrimidines (therapeutic use)
• Receptor, Platelet-Derived Growth Factor alpha (genetics)